Archive for the ‘General Cancer Research’ Category

Cancer Charity Sues Private Firm Over Alleged Research Use

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Posted 03 Jan 2012 — by James Street
Category Finance and Politics of cancer research and treatment, Fraud, Legal Issues

January 3, 2012, 10:41 am

A cancer-research organization is seeking more than $1-billion in damages from a biotechnology company it claims is developing drugs based on work funded by the nonprofit group, according to The Boston Globe.

The suit filed last month by the Leonard and Madlyn Abramson Family Cancer Research Institute accuses Agios Pharmaceuticals of Cambridge, Mass., and its co-founder, Craig B. Thompson, of taking its intellectual property to launch a for-profit business.

Dr. Thompson led the University of Pennsylvania-affiliated institute from 1999 until last year. The charity contends Agios’s work on drugs to suppress cancer cells is based on novel research conducted during his tenure there and that Dr. Thompson did not disclose to the institute that he had started the firm, which has secured tens of millions of dollars in investments and a licensing deal.

Dr. Thompson, who is also the chief executive of New York’s Memorial Sloan-Kettering Cancer Center, denied the allegations, asserting in a written statement that they are “unfounded and without merit.”

Russians find new way of curing cancer

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Posted 03 Jan 2012 — by James Street
Category antiangiogenesis, Osteosarcoma
Jan 2, 2012 21:57 Moscow Time

© Фото: en.wikipedia.org
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Scientists from the Russian Central Institute of Orthopedics and Traumatic Surgery have created a new method of treating cancer.

The method still has been used only as an experiment, but has already won the approval of foreign experts.

Every tumor has its own “network” of blood vessels, and to stop its growth, these vessels must be blocked so that the tumor would not be feed with blood anymore. Thus, the inventors of the new method have suggested to block them with special granules. For vessels of a larger diameter, instead of granules, metal spirals are used. When introduced into a patient’s body, these spirals go through his or her arteries and unfold themselves when they reach the place of their “destiny”.

To introduce these granules and spirals into a patient’s body, only an injection is needed.

“In fact, the procedure is no less traumatic than a prick of a syringe,” one of the creators of the new method, Professor Alexander Balberkin, says. “But it is very effective – at least, according to preliminary data. However, it still cannot be recommended as a universal method – it is effective only if combined with other methods.”

Unfortunately, the new method is ineffective against some kinds of tumors. For example, it is hard to stop the growth of a gristle tumor by it. Still, the method has proven to be effective against bone or bone marrow tumors and can be recommended to patients for whom an operation is contraindicated.

“However, the new method still needs a more thorough approbation,” Professor Balberkin says.

“We have conducted about 600 operations,” he says, “but we still don’t have reliable statistic data. It is too early to sum up the results – some time must pass so that we are able to watch the condition of our patients. At the same time, we can already say that, at least in some cases, the results may be positive. For example, a new method may be useful while preparing a patient for an operation – it enables to lower the blood losses several times.”

Professor Balberkin says that doctors from Kazakhstan and other former Soviet republics already show great interest in the new method. Moreover, German oncologists are already using it quite successfully for curing uterine cancer, kidney cancer and spine tumors – although, at first, German doctors were very skeptical about the method suggested by their Russian colleagues.

The cutting-edge research which could save thousands of lives at Cardiff’s Cancer Research UK Centre

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Posted 03 Jan 2012 — by James Street
Category Understanding Cancer

Scientists at the Cancer Research UK Centre in Cardiff are carrying out cutting-edge research into the disease. Health Editor Madeleine Brindley profiles some of their work

THE Cancer Research UK Centre in Cardiff concentrates its groundbreaking work on urological, breast and blood cancers and on cancer prevention.

Dr Chris Pepper, is a reader in haematology at Cardiff University and leads the centre’s research into chronic lymphocytic leukaemia (CLL).

He said: “Our research breaks down into three main areas, all of which are very patient-focused. The vast majority of our research is done by looking at cells from patients who come into the clinic.

“The first of those areas is the identification of new prognostic markers.

“It is really important to identify up front, when a patient first presents with disease, whether they are going to require early treatment or whether we can just monitor their disease.

“We’re entering an era of personalised medicine, and the ability to accurately determine the clinical course of an individual patient’s disease is a major priority.

“This is particularly pertinent in CLL because of the very different clinical outcomes associated with this disease.

“The worst type of CLL is just as bad as any leukaemia – survival rates are less than two years.

“In contrast, about a third of the patients we see have a leukaemia that never progresses and they will probably die of old age rather than from the disease,” he added.

“We’re now trying to look at the biology of the disease to see if we can identify those patients who need treatment right now – probably about a third – and another third who will progress at some point down the line.

“We’ve made some significant progress down that road in work I’ve been doing with my colleagues Dr Duncan Baird and Dr Chris Fegan.

“We now understand that some patients undergo an awful lot more cell proliferation, meaning the cells divide more and more, although this doesn’t necessarily manifest itself in an increased tumour burden, so can’t be detected by a routine blood test.

“We’ve been looking at telomeres, which are found on the ends of chromosomes and are like a biological clock, because they shorten every time a cell divides.

“Their primary role is to protect the integrity of our genetic material, but as they get shorter they start to lose their protective function.

“We’ve discovered that when they reach a certain length they become unstable, and the chromosomes stick together when the cells divide, driving genetic instability.

“The chromosome material gets muddled up as a result, genes get deleted or moved.

“We think this is the key driver of disease progression in many cancers, not just CLL.

“As these cells keep dividing, they become more and more unstable, which confers a bad prognosis to a patient, because their genetic material is constantly being altered, making the cancer much more difficult to treat.

“In addition to telomere length, we have also identified a molecule called NF-kappaB,” he revealed.

“This molecule is a master regulator of hundreds of different genes, many of which are associated with the control of processes that could result in cancerous changes.

“We’ve shown that by measuring the levels in patients, it allows us to predict whether an individual patient will respond to conventional chemotherapy.

“If they have high levels, they relapse very quickly on conventional therapy.

“The second part of our work is basic tumour cell biology.

“We’re trying to understand what’s driving the malignancy; why do some patients have a very stable disease while others rapidly progress and require chemotherapy.

“It has become increasingly clear that one of the key determinants of disease progression is the ability of the tumour cell to change the micro-environment they exist in. We want to know how.

“People tend to think of cancer as a foreign invader, but it’s not.

“A cancer is essentially yourself, but it has changed subtly from the other cells in your body, which makes it very difficult to identify and to eradicate using your body’s own defence mechanisms.

“In the case of CLL, the disease actually uses the immune system to promote cancer cell survival.

“Work that we have recently published with another colleague, Dr Steve Man, indicates that in the early stages of the disease the immune system probably tries to mount a response to the cancer but once that fails the tumour grows.

“Those same immune system cells are changed by the environment the cancer cells create, making them produce different chemicals which support the growth and the survival of the tumour, making it difficult to treat.

“Our third area of work is to develop novel therapies – we have been involved in the development of a number of new treatments for CLL, including more targeted agents that specifically attack the tumour cell.

“The latest class of drugs we are testing are able to alter the environment tumour cells live and grow in to make them more sensitive to the standard therapies.

“These drugs look set to make a valuable addition to the treatment options for this disease in the near future and we hope that some of them will be trialled here in Cardiff.”

The Power of Preservation: Minimally Invasive Lung Cancer Treatment at South Nassau Communities Hospital

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Posted 03 Jan 2012 — by James Street
Category Lung Cancer, Osteosarcoma surgery, Surgery, Surgery, Thoracic Surgery

A decade ago, a lung cancer diagnosis left both patients and physicians with few options. Today, while surgery remains the gold standard, the approach to this treatment has changed. Thoracic surgeons at South Nassau Communities Hospital are forging innovative surgical ground and safeguarding patients’ lungs.

According to the American Cancer Society, 221,130 new cases of lung cancer will be diagnosed in 2011. Almost 17,000 cases of esophageal cancer will be diagnosed, and, though the incidence rate is extremely low, patients with these types of cancers can develop tumors within and around the heart. Before 2004, Long Island residents with disease of the chest cavity made the long trek to Manhattan for consultations, treatments and follow-up care.

With the arrival of Shahriyour Andaz, M.D., FACS, FRCS, Director of Thoracic Oncology at South Nassau Communities Hospital and associate professor in the Department of Surgery at Hofstra University, two principles of thoracic care on Long Island have shifted significantly. Patients now have an alternative to Manhattan medicine, and with the investment in advanced technologies at South Nassau Communities Hospital, they also have an alternative to traditional open chest surgery.

“In the past, surgeons would make a large incision to cut the ribs and access the chest. That was a painful operation, so we’ve moved away from major incisions to doing smaller and smaller cuts,” says Dr. Andaz. “Now, 80% to 90% of all the cancer we take out is done through small, minimally invasive incisions.”

A Renaissance of Surgical Technique

The robotic da Vinci Surgical System offers Dr. Andaz and his colleagues in the thoracic oncology program the visualization and maneuverability necessary to promote minimally invasive approaches to technically demanding procedures. The three-dimensional views and flexibility of robotic hands, which are carefully controlled by the surgeon, facilitate the delicate dissection of blood vessels and the resection of the lungs’ lobes through centimeter-long incisions.

In the case of a video-assisted thoracoscopy, which allows the surgeon to evaluate the chest cavity for lung cancer or remove a tissue sample for further analysis, the da Vinci Surgical System has supplanted the need for an open chest thoracotomy. Dr. Andaz makes two or three small incisions between the ribs, and the lung is deflated to allow for a greater space between the lung and chest wall. That vantage point provides access to the lung for an endoscope, which Dr. Andaz uses to view and sample any potentially malignant tumor on the lung. The sample is then sent to the laboratory for pathological testing.

While the da Vinci Surgical System is utilized for general, gynecologic, kidney, prostate and urologic procedures, the technology allowed Dr. Andaz to become the first health care provider on Long Island to perform a robotic thymectomy and robotic bilobectomy in 2010 and 2011, respectively.

Operating Across the Aisle

“Most surgeons will not do a bilobectomy for central tumors — the type of tumor that straddles the airway and involves blood vessels stuck to the tumor,” says Dr. Andaz. “The da Vinci can help with the tedious process of dissecting those blood vessels.”

The complexity of a bilobectomy is grounded in the need to remove both the lower and middle lobes of the lung — leaving only the upper lobe — to ensure that wide enough margins are created and no cancer cells are left behind. In addition, the complex network of blood vessels stretching over the fissures in the lungs poses a challenge in cleanly resecting the necessary portions of the lung.

To begin, the attending anesthesiologist puts the patient under and slowly deflates one lung. Dr. Andaz then makes four 2-centimeter-long incisions in the chest wall and guides the da Vinci Surgical System’s robotic arms into the chest through the incisions, allowing him to concentrate on excising the lower lobe. The precise instrumentation divides the blood vessels and pulmonary vein from the lung tissue without disrupting the blood flow to the heart.

Next, Dr. Andaz exposes the fissure between the lower and middle lobes to allow for visualization of the pulmonary artery. With the three-dimensional da Vinci Surgical System camera, he is able to safely encircle and divide the branches leading to the lower lobe. After removing the lower lobe tissue, 
Dr. Andaz begins dissecting the pulmonary artery branches to the middle lobe. That separation allows him to dissect and divide the bronchus to the middle and lower lobes.

Dr. Andaz explains that the ability to remove both the lower and middle lobes of the lung can often depend on how much reserve a patient has in his or her lungs. The resection of one lobe diminishes lung function by 10% to 15%; the loss of two lobes results in a 20% to 25% reduction in total capacity; and the removal of all three lobes — the entire right lung — equals a 40% to 50% loss of the combined lung capacity. All surgical candidates undergo pulmonary function testing before being cleared for robotic surgery.

After the final tissue resection, Dr. Andaz retracts the da Vinci Surgical System’s arms and closes the incisions while the anesthesiologist carefully re-inflates the lung. Patients typically remain in the inpatient unit at South Nassau Communities Hospital for four to five days.

Tackling the Thymus Gland

Just as the da Vinci Surgical System has allowed Dr. Andaz and his colleagues to move away from the open chest thoracotomy, the technology has opened up new avenues for removing the thymus gland. The traditional procedure involved splitting the sternum with a major incision to access the chest cavity. Dr. Andaz can perform a robotic thymectomy instead, which approaches the organ — located in a tight space between the heart and the breastbone — through small incisions placed on the side of the patient.

“Usually, as a person ages, the thymus gland — like the tonsils — becomes smaller and almost disappears,” says Dr. Andaz. “For some people, however, the thymus gland continues to grow and enlarge and can lead to myasthenia gravis, an autoimmune disease that allows small proteins to cling to muscle receptors and leads to a neuromuscular disorder.”

Myasthenia gravis can present through symptoms centering on fatigue, including drooping eyes, difficulty breathing, chewing and swallowing, and weakness in the arms and legs. As Dr. Andaz explains, removing the thymus gland in patients with the condition can provide significant relief for their symptoms.

For the robotic procedure, 
Dr. Andaz makes three 2-centimeter incisions at the side of the chest for lateral access. Seated at the da Vinci Surgical System console, Dr. Andaz manipulates the robotic arms to find the thymus gland behind the breastbone. He then completes the delicate separation of the gland from the adjacent fat, pericardium and the innominate vein.

After resecting the thymus gland, Dr. Andaz closes the incisions, and the anesthesiologist re-inflates the lung. Patients typically spend one to two days in the hospital and are back to work in one or two weeks.

Targeting the Right Site

For lung cancer patients whose poor lung reserves eliminate them from the surgical candidate pool, radiation has traditionally been the next treatment option. The choice is often made in an attempt to conserve what little function the lungs have. However, standard radiation often poses a significant threat not only to the tumor, but also to the surrounding healthy tissue.

“The problem with standard radiation is that the treatment can essentially cook the entire lung. The radiation can damage the surrounding lung tissue, which is difficult for someone who has poor lung reserve to begin with,” says Dr. Andaz. “The Novalis Tx radiosurgery technology uses advanced computerized techniques to focus an intense radiation beam on the tumor site only to preserve the rest of the lung.”

The radiosurgery platform offers a noninvasive, customizable treatment alternative to surgery. The system’s mechanical accuracy is within 0.5 millimeters of the tumor site during treatment, while the MV Portal Vision allows radiation oncologists to view the exact location of the tumor as the system targets it.

The Novalis Tx is also equipped with gating features to adapt the radiation to the patient’s natural respiration cycle. In addition, the system reduces the requisite number of treatments as compared to the standard radiation therapy. Patients undergo treatment once a week for only three to four weeks rather than six weeks.

The Communal Process

Every month, the specialists within the thoracic oncology program meet for a program-specific tumor board. The conference reviews patient cases one by one for insight from each physician, even those not directly involved in the treatment, which allows for a dynamic and multifaceted discourse. Medical oncologists, pathologists, pulmonologists, radiation oncologists, radiologists and surgeons are joined by primary care physicians to evaluate a patient from every possible perspective.

“These are very complicated decisions, and it requires lots of people to be involved in the decision-making process,” says Dr. Andaz. “I’m very open to the discussion of alternatives to the management of the case.”

In addition, staff with the thoracic oncology program participate in the weekly tumor board at South Nassau Communities Hospital and meet on a need-appropriate basis between the established conferences.

To learn more about thoracic oncology at South Nassau Communities Hospital, visit www.southnassau.org and click on “Surgical Services” and “da Vinci Robotic Surgery” under the “Services/Specialty Centers” tab.

 

A Measure of Change in Lung Cancer Detection

To maximize the rate of survival among women with breast cancer, the American Cancer Society recommends every woman receive a mammogram annually after age 40. To increase the survival rate among men and women diagnosed with colon cancer, the organization advises people older than 50 undergo a colonoscopy every 10 years. Now, lung cancer has a similar screening recommendation.

A 1991 initiative launched by a group of physicians from Cornell University Medical Center — investigating the impact of helical computed tomography (CT) imaging on the early detection of lung cancer — discovered that, when caught in Stage I, lung cancer isn’t as deadly.

“The traditional data has shown the overall survival rate is 15% at five years, meaning that 85% of patients will die,” says Shahriyour Andaz, M.D., FACS, FRCS, Director of Thoracic Oncology at South Nassau Communities Hospital and associate professor in the Department of Surgery at Hofstra University. “The participants in the Cornell study showed a survival rate far superior than any other data we have: 90% at 10 years. Even though lung cancer is three times as prevalent as breast cancer, there has been no test to detect early lung cancer — until this.”

In fact, the initiative has developed protocols to a) identify high-risk patients, b) distinguish between benign and malignant nodules detected by the CT scan, and c) determine when to biopsy or monitor the nodules, as well as timetables for when to follow up with patients. The International Early Lung Cancer Action Program (I-ELCAP) includes 48 institutions in nine countries, including South Nassau Communities Hospital, where Dr. Andaz pioneered the program.

Dr. Andaz recognized the significance of the I-ELCAP, and for the last three years, South Nassau Communities Hospital has contributed data to the program while offering free CT scans for high-risk patients in the community. The data is then sent to Mount Sinai Medical Center and incorporated into the I-ELCAP database. According to Dr. Andaz, of the 800 to 900 patients imaged at South Nassau Communities Hospital, 30 have been diagnosed with lung cancer, and 90% of the cases were detected within Stage I.

 

Has an achilles’ heel for cancer been found?

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Posted 03 Jan 2012 — by James Street
Category Colon Cancer, DNMT1, genetic research, MBD2

RESEARCH into a gene called MBD2 could lead to new treatments for colon cancer, after experts discovered that switching it off prevents tumours from forming.

The breakthrough has been described as a “potential Achilles’ heel” by lead research Professor Alan Clarke.

It comes from the work at the Cancer Research UK Centre in Cardiff into how genes and proteins are involved in the formation of cancer.

Prof Clarke said: “The interesting thing about cancer is that one of its primary features is to turn off a number of defensive mechanisms. As the cancer develops, these defensive mechanisms are got around, usually because the genes are switched off or deactivated.”

 The first breakthrough came with the discovery of the DNMT1 gene, which, when switched off meant that cancers couldn’t develop.

But deactivating DNMT1 also had a significant effect on other bodily functions, meaning it would not make a good target for cancer therapies.

MBD2 belongs to a family of proteins which turn off other genes and research carried out in Cardiff has found that deactivating it prevents colon tumours from developing.

“It’s fantastic and does it with virtually 100% efficiency,” Prof Clarke said. “And, taking out MBD2 isn’t that damaging to other tissues and systems – it appears to be tolerated reasonably well.

“Therefore, if we were to have a therapy targeting MBD2, any off-target effects would be limited.”

The research team has been examining the impact of MBD2 by creating mice which lack the gene. But many questions remain unanswered.

Prof Clarke said: “We have to show that if you don’t have MBD2 then the likelihood of getting a tumour is much reduced. And we don’t know if you take out MBD2 from a tumour whether it will disappear.

“We’ve been trying to develop a drug that specifically targets MBD2 but, unfortunately, attempts have not been successful because it’s a very difficult protein.

“We think that MBD2 deficiency suppresses tumorigenesis by failing to turn off a number of genes – some these will be important. We’re trying to delve down and find out which of the genes it regulates are important.

“We have a potential Achilles’ heel here to stop tumours forming and we’re also trying to find a drug target.

“We can imagine that this will be useful for patients who have had a tumour and have had therapy but who have a chance of relapsing. But we’re also testing the notion that regulating MBD2 will cause tumours to regress.”

Prof Clarke added: “The remarkable thing about the way we treat cancer is that we’re stuck with pretty much ancient technology.

“We mostly use poisons but although we have made progress with virtually all forms of cancer in terms of improving treatment, if we are going to make a huge step change it will have to come from a better understanding of the mechanisms that lead to cancer.

“That will come from a molecular understanding of cancer – if we really understand the molecular basis we can create drugs that make a big difference rather than small, incremental differences.”

Prediction for 2012: Medicine gets closer to treating cancer with vaccines.

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Posted 03 Jan 2012 — by James Street
Category Vaccine


Radiation and chemotherapy reign as the go-to treatments for cancer, but for 20 years researchers also have been exploring the use of therapeutic vaccines. In 2012 that work may come to fruition.

“It’s an exciting time for cancer vaccine development,” said Dr. Larry Kwak, professor and chairman of lymphoma and myeloma at the University of Texas M.D. Anderson Cancer Center in Houston.

“What’s especially impressive is the diversity of cancer vaccine. It bodes well for what you’re going to be seeing in the future,” Kwak said.

More than 250 clinical trials of vaccines, including 34 for breast cancer, are under way, according to the National Cancer Institute.

Like other vaccines, cancer vaccines use a chemical marker of a disease (in one case, a virus; in another, a malignant tumor) to train a person’s immune system to fight the disease.

But unlike vaccines for the flu or chicken pox, which are preventive, “we almost uniformly vaccinate after cancer is there,” Kwak said.

Some cancer vaccines in development could be administered to many people, while others – including Kwak’s vaccine for follicular lymphoma – would have to be tailored to each patient’s tumors.

Kwak’s vaccine has passed Phase III trials and is moving toward the final steps of regulatory approval.  The U.S. Food and Drug Administration approved the first cancer vaccine, called Provenge, in the spring of 2010 for the treatment of prostate cancer. A vaccine for melanoma performed well in the final stages of clinical trials last year.

“What ties them together is they are activating the immune system so it’s primed and ready to fight,” Kwak said.

The National Cancer Institute reports there are ongoing clinical trials for therapeutic vaccines to treat bladder, breast, cervical, kidney, lung, pancreatic and other forms of cancer.

John Kanzius Human Size Cancer Killing Machine Ready

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Posted 28 Dec 2011 — by James Street
Category Kanzius Machine, Physics and Engineering, Radiation, Radiation
December 28, 2011
It’s been a long time coming, seven years to be exact, but a device large enough to accommodate a human patient has been the latest in a series of new developments in the John Kanzius Cancer Research project.
Kanzius’ radio frequency device works by emitting radio waves that heat and kill cancer cells targeted with nanoparticles, microscopic pieces of gold and other metals that are injected into the bloodstream. The device has proven to kill pancreatic cancer cells in live mice without harming healthy tissue but a larger device was needed before Kanzius’ invention could be tested on humans. The earlier devices can only accommodate petri dishes and small animals like mice and rabbits. The announcement of the larger device was made in Erie, Pennsylvania last week by Marianne Kanzius, widow of Sanibel islander John Kanzius who died two years ago of a rare form of leukemia. Marianne Kanzius is managing partner of Thermed LLC, the company formed by John Kanzius to develop the technology. The new machine is a fifth generation model. Development of the larger machine is necessary before the Food and Drug Administration (FDA) can approve human trials for the device. “It can support up to 800 pounds,” said Charlie Rutkowski, plant manager at Industrial Sales & Manufacturing, the Millcreek, Pennsylvania company that manufactures the Kanzius devices.
Besides being large enough to treat large animals and humans, the newest Kanzius device is also easier to operate. Earlier versions must be fine-tuned constantly. The fifth-generation device is more automated. Rutkowski said work is already underway on a sixth generation device. Tests must be performed on larger animals before the FDA approves clinical trials for humans. Thermed has not formally approached the FDA to request clinical trials. Lee Memorial Health System is one of five designated locations for human trials. Stephen Curley of the MD Anderson Cancer Center in Houston said last week, “This (larger machine) will mean we can begin large animal modeling studies that will be necessary to understand the RF (radio frequency) dosing and treatment times in human patients.” He could not comment on the time to human clinical trials indicating they are bound by FDA guidelines but human trials are estimated to be at least two to three years away. In an interview last week with The Erie Times Marianne Kanzius said Thermed has reached a research contract with one major research center and is negotiating with two others. “This is the business end of John’s dream,” she said. “I know John would be pleased with how things are going.” Kanzius began working on the technology after he was diagnosed with cancer.
His death two years ago threatened to derail the project but the positive results of research have kept it alive and thriving.

An ambitious plan for curing cancer in a businesslike way is in the works

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Posted 28 Dec 2011 — by James Street
Category Bioinformatics, Finance and Politics of cancer research and treatment, General Cancer Research, genetic research, Proteomics, Proteomics, Research Centers, Understanding Cancer

Dec 31st 2011 | NEW YORK | from the print edition

 

Cancer, you have a problem

RON DEPINHO is a man on a mission. Oddly, though, he does not yet know exactly what that mission is. Dr DePinho is the new president of the MD Anderson Cancer Centre in Houston, Texas. (He took over in September, having previously headed the Belfer Institute, part of Harvard’s Dana-Farber Cancer Institute.) Mindful of his adopted city’s most famous scientific role, as home to Mission Control for the Apollo project, he says his own mission is akin to a moon shot. He aims to cure not one but five varieties of cancer. What he has not yet decided is: which five?

That it is possible to talk of curing even one sort of cancer is largely thanks to an outfit called the International Cancer Genome Consortium. Researchers belonging to this group, which involves 39 projects in four continents, are using high-throughput DNA-sequencing to examine 50 sorts of tumour. They are comparing the mutations in many examples of each type, to find which are common to a type (and thus, presumably, causative) and which are mere accidents. (The DNA-repair apparatus in malignant cells often goes wrong, so such accidents are common.)

The consortium’s work is progressing fast, and preliminary results for many tumours are already in. But such knowledge is useless unless it can be translated into treatment. That is where Dr DePinho comes in—for his career has taken him into the boardroom as well as the clinic. He is a serial entrepreneur: he helped found Aveo Pharmaceuticals, which is developing a drug to block the growth of blood vessels in tumours, Metamark Genetics, which works on diagnosing cancers, and Karyopharm Therapeutics, which is trying to regulate the passage of molecules into and out of the cell nucleus, and thus control the nucleus’s activities. His aim in coming to MD Anderson, he says, is to “industrialise” other aspects of biological research in the way that genetics has been pushed forward by high-throughput sequencing.

That will cost billions of dollars. Fortunately, the state of Texas—no pushover when it comes to spending taxpayers’ cash—is creating a $3 billion cancer-research fund to help pay for it. Local philanthropists, including T. Boone Pickens and Ross Perot, are chipping in, too. Their model is the original Human Genome Project, during which the cost of sequencing a single genetic “letter” (a DNA base pair) fell from $10 in 1991 to ten cents in 2001—and is now 3,000 base pairs a cent. They hope their dollars will encourage people working with what are now, essentially, craft technologies to think about how they might industrialise them.

Several techniques look ripe for such industrialisation. Dr DePinho sets great store, for example, by the use of genetically modified mice (he calls them “little patients”) in which mutations found in human cancers can be replicated precisely, but one at a time, to discover the shape of each piece of the jigsaw. If this process can be scaled up it will, as he puts it, allow cancer’s genetic generals to be distinguished from the foot soldiers.

Another field that has great potential is imaging technology—in particular, a combination of positron-emission tomography (which uses radioactive sugar to measure how metabolically active tissue is) and computerised tomography (which uses X-rays to map the body’s internal anatomy). Together these can show whether a treatment is reducing a cancer’s energy consumption, and thus its metabolism. This gives a good indication of how well that treatment is working.

A family business

Dr DePinho himself will have more duties at MD Anderson than just dealing with the five chosen tumours. The donkey work of creating the Institute for Applied Cancer Science, as the new mission control is to be known, will be done by Lynda Chin. Dr Chin, too, worked at the Belfer Institute. She is part of the International Scientific Steering Committee of the cancer-genome project. And she is also Dr DePinho’s wife. Dr Chin will be assisted by some 55 other scientists from the Belfer, who are making the journey to Texas with her and her husband. That sort of team poaching is common in investment banking but rarer in academic research. Dr DePinho refers to it, jokingly, as metastasis, since a clone of his primary creation will be taking root elsewhere in the country.

As to which five cancers to attack, that decision will be made by the middle of 2012. A crucial consideration will be how likely it looks that research into the tumour in question could get rapidly to the “proof of concept” stage—the point at which it could be taken forward by a business that relied on commercial sources of capital, rather than on the sorts of grants that usually propel academic research. At that moment a new firm might be spun out of the institute, or a deal might be done with an established pharmaceutical firm, to try to get a new drug developed.

In recent years many big drug companies have gutted their research departments. This is partly because those departments have failed to come up with new “blockbuster” drugs of the sort that created Big Pharma in the first place, and partly because the big firms’ bosses had hoped that smaller biotechnology companies, of the sort Dr DePinho has helped set up, would do the hard work of drug discovery instead, and then let themselves be bought by the big firms.

Unfortunately, it hasn’t quite worked out like that. The output of the biotech firms has been a trickle, rather than a torrent. They have been one of the worst-performing parts of the private-equity market since 2007, according to Dr DePinho. He hopes to change that—and in the matter of new anti-cancer drugs, the science is looking auspicious. For example, a drug called vemurafenib, which was approved for use in America in August 2011, gives months of extra life to people with metastasising melanoma, one of the deadliest cancers. Vemurafenib is so powerful that some people call it a “Lazarus” drug, after the chap Jesus is said to have raised from the dead.

Crucially for Dr DePinho’s project, the development of vemurafenib was stimulated by the identification of a mutated gene often present in melanomas. He and others like him hope that the cancer-genome consortium will throw up dozens of similar genes, and that they, too, will prove tractable targets for drug development.

Of course, if Dr DePinho had a penny for every time a “cure for cancer” headline proved premature, he wouldn’t need munificent donors. But if his bets on the science and on adopting business methods pay off, the drug industry and millions of patients will benefit. That would be one benign sort of metastasis.

On leaping to conclusions about a neurosurgeon and Dr. Stanislaw Burzynski

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Posted 27 Dec 2011 — by James Street
Category antineoplasms, Complementary and Alternative Medicine, Finance and Politics of cancer research and treatment, Fraud, Medical Blogs, Surgery

Category: Alternative medicine • Cancer • Medicine • Surgery
Posted on: December 27, 2011 10:45 AM, by Orac

Another Christmas is over, and we’re settling in to that strange week between Christmas and New Years when, or so it would seem, most of the world isn’t working except for retail. I’m half taking the week off from work in that I don’t plan on going into the office if I can possibly avoid it, but will be starting up a couple of grants for the February/March NIH cycle and dealing with a couple of nagging issues left over from before the holidays. Regular readers might have noticed that ScienceBlogs had a bit of a glitch beginning sometime in the early morning hours of Christmas morning and not ending until yesterday sometime. In essence, although you could read the blogs, you couldn’t comment, and all the bloggers were locked out of the Movable Type back end. Since that provided me an excellent excuse to take a day off from blogging, I did. I was still recovering from the food and wine coma of the last two days anyway and probably didn’t have anything coherent to say, if I ever do.

But what should await me this morning when I decided to take a look and see if ScienceBlogs were fully up and running again? It’s something I had hoped to be able to ignore until 2012, having blogged enough about it over the last month or so. I’m referring to the “brave maverick” cancer doctor Stanislaw Burzynski and his Burzynski Clinic. Read the links for the full, Orac-ian deconstruction of what Burzynski appears to be doing, but the brief version is that he uses what he calls antineoplastons, which he claims to have originally isolated from urine back in the 1960s and 1970s but now synthesizes chemically, to treat cancer. It turns out that these antineoplastons are nothing more than the metabolic products of a real drug, phenylbutyrate. This is a drug that was initially used to treat urea cycle disorders but has also shown (very) modest promise in treating some forms of cancer and that these days Dr. Burzynski appears to be switching over to using off-label phenylbutyrate but still calling it “antineoplastons” and charging outrageous sums of money to his patients. In addition, these days, seeing a profit opportunity, he’s jumped on the genomic bandwagon–incompetently–and started offering what he calls “personalized, gene-targeted therapy,” which, when looked at more closely, is really nothing more than a simplistic use of a commercially available test to pick out a witch’s brew of chemotherapy, targeted therapies, and antineoplastons phenylbutyrate, put together with little or no thought to synergistic toxicities or whether they interfere with each other’s actions or not. All of this, he sells as being “not chemotherapy” (it is; it’s just incompetently administered chemotherapy) and “natural” (it’s no more natural than taxol, which was originally derived from the bark of the Pacific yew tree and turned into a chemotherapy drug). Through all of this, Burzynski has tried, through his PR flack, to silence bloggers who criticize him and thereby protect the lucrative cult of personality he’s built around his name. Now, it appears that there is another aspect of Burzysnki’s practice I need to comment on, as mentioned on Pharyngula (crossposted here) and Furious Purpose, and that’s physicians who send their patients to Burzynski.

By way of background, I’ve noted before that there is a particularly disturbing aspect of Burzynski’s practice. That’s how his patients, convinced that Burzynski can save them (or, if they’re parents, that he can save their child) will, understandably go to extreme lengths to raise the often hundreds of thousands of dollars Burzynski charges to apply his science-y-sounding woo to cancer. It is not at all uncommon for these families set up charities designed to raise money, or, as I put it a couple of years ago, to harness the generosity of kind-hearted strangers to pay for woo. In fact, it was a couple of high-profile cases, one involving U.K. performer Peter Kay, who did two charity concerts for a Burzynski patient, that originally brought the attention of the skeptical blogosphere on Burzynski. More precisely, it was the reaction of one Marc Stephens, who claimed to represent the Burzynski Clinic and in that claimed capacity issued legal threats against bloggers, that brought the attention (and wrath) of the skeptical blogosphere down on Burzynski. In any case, I thought that that was the worse aspect of Burzynski’s activities, that he seemingly encouraged his patients with terminal cancer to go to such lengths to raise money, the better to enrich himself. There is now, however, another aspect that could be at least as disturbing. I haven’t made up my mind yet, because I don’t know if what I’m learning about this aspect of Burzynski’s activities. If what PZ and Furious Purpose write is accurate, then Dr. Teo is about as unethical as it gets. However, I suspect things are not as simple as what is being written.

Meet Dr. Charles Teo, a neurosurgeon currently in Australia. Apparently, he has a history of funneling patients to Burzynski, although it’s not clear at all to me whether it’s Dr. Teo who promotes Dr. Burzynski or whether he’s just working with patients who have decided to go to Dr. Burzynski. For example, here is one patient description cited:

After much research and the help of many friends we discovered Dr Charles Teo from Prince of Wales Private Hospital in Sydney, who performs surgery on inoperable brain tumors. Dr Teo is a neurosurgeon who has pioneered a method of minimally invasive brain surgery and has successfully performed around 5000 operations. Dr Teo has offered to operate on David and at this stage the operation is scheduled for Friday, 20th September 2002. David, with the support of his family will fly to Sydney on Wednesday, 18th September 2002.This process is not a cure, however, it is designed to relieve the pressure by reducing the size of the tumor, he will need further treatment to kill off any remaining pieces of the tumor. The treatment being researched at the moment is antineoplastons treatment which is administered by the Burzynski Clinic in Houston, USA.

One notes that this is from 2002 and 2003 and that it is not at all clear from the description above that Dr. Teo suggested that this family go to visit Burzynski or that this patient is evidence of Dr. Teo taking advantage of dying patients.

In all fairness, this case is a bit more damning:

However, Braydon’s mother Zoe Cobb hoped the Sebastopol toddler could begin treatment soon at the Burzynski Clinic in Houston, Texas.”We’ll talk more about it with Charlie (Dr Charles Teo) this afternoon,” Zoe said. “We’re just off for the MRI scans now.”

The Burzynski Clinic, named after founder Stanislaw Burzynski, specialises in individual cancer treatments.

Zoe said they had discussed taking Braydon to Texas with Dr Teo, who said he felt it would be a good option for the four-year-old.

However, before you decide, take a look at this video:

And this one as well:

There is a type of surgeon who represents the true “brave maverick” in that he is highly skilled, highly confident, and willing to take on seemingly “hopeless” cases. Surgeons like this will often, as described above, operate on patients who have either been operated on before by other surgeons who couldn’t fix what was wrong or been turned down by other surgeons as “inoperable.” Of course, “inoperable” is not a hard-and-fast word in that what is inoperable to one surgeon might well be operable to another. It’s also a very fine line in that this is an area where science- and evidence-based medicine collide with personal surgical skill. There are surgeons out there who are just so good that they can physically do with their hands what other surgeons, talented and experienced as they might be, cannot. Alternatively, they are far less risk-averse than the typical surgeon in their specialty and are therefore willing to attempt things that other surgeons won’t, such as the resection of “unresectable” brainstem tumors. Where daring ends and recklessness begins is a very fuzzy line with surgeons such as these. When they fail, they fail spectacularly, but when they succeed sometimes the result is the patient described in the video above. Surgeons such as these might very well cause a lot of complications and unnecessary suffering through aggressive–even reckless–pushing of boundaries. However, they also push the envelope (which Dr. Teo even says explicitly that he is trying to do in the second video), which can lead to advances in surgery and can sometimes save patients thought to be unsavable. Where the balance between the harm and good done by such surgones lies is, again, not a trivial thing to figure out.

It probably doesn’t help that Dr. Teo has other aspects of the “brave maverick” doctor. For example, if you search for his name plus “cell phone cancer,” you’ll find a plethora of articles and videos featuring Dr. Teo warning against the dangers of cell phones as a cause of brain cancer:

Brain cancer surgeon Charlie Teo has urged people to put mobile phones on loudspeaker, move clock radios to the foot of the bed and wait until microwaves have finished beeping before opening them.The controversial Sydney specialist told a Melbourne fundraiser that although the jury was still out on mobile phones and other forms of electromagnetic radiation, we should not take risks.

“Even though the jury’s not in, just to err on the side of safety I would try and limit the amount of electromagnetic radiation that you’re exposed to,” he said.

“The American government, for example, recommends that all electrical appliances should be put at the foot of the bed and not the head of the bed.

Then there’s this video:

At around the 3:35 mark, Dr. Teo is featured saying unequivocally that he believes mobile phones can cause brain cancer. Later, the reporter engages in a blatant bit of fear mongering by noting that mobile phones use microwaves and you wouldn’t think of putting your ear up next to a microwave oven.

The stupid in that video, it burns brightly, rather like what would happen if you put metal in a microwave oven.

So, we can see that Dr. Teo is not a very good judge of epidemiology or basic science. Yes, I’ve refused to concede on many occasions that a link between cell phones and cancer is physically impossible, as some physicists have unwisely done based on a Cancer Biology 101 understanding of cancer, but I do consider it incredibly implausible that there is such a link. Maybe not homeopathy-level implausible, but almost. Also, as I (and others) have pointed out time and time again, not only is a link between cell phones and cancer incredibly implausible based on what we know about physics and biology, but the epidemiological evidence is overwhelmingly against such a link existing. There’s no convincing evidence for an increase in the incidence of brain cancers and no good evidence that the laterality of brain tumors correlates with the side of the head people hold their phones to. In brief, there is no good reason, based on prior plausibility informed by basic science or on epidemiological evidence, to think that mobile phone radiation causes brain cancers.

But Dr. Teo believes it does, which makes me think it’s not all that much of a stretch to think that he would be susceptible to the fancy-sounding blandishments of a charlatan like Dr. Burzynski.

And that’s why I think that what’s more likely to be going on here is something way more nuanced than what PZ and Furious Purpose think. Subject to change as more information comes in, I reject, based on what I’ve been able to find out thus far, the contention that Dr. Teo is operating on patients with inoperable brain cancer in order to make money off of them. Certainly neither PZ nor Furious Purpose have made a convincing case for that. A far more likely explanation is that Dr. Teo is one of those “cowboy surgeons” who will operate on risky patients that other surgeons won’t. When he agrees to operate on someone with an “inoperable” brain cancer, from what I can tell he almost certainly believes that he can do what other surgeons can’t: Remove the tumor and possibly cure the patient. It appears that, often enough, he’s right. Based on what I’ve been able to find out, unless there is more information that I’m not aware of, I have little choice but to say that I consider it at best highly irresponsible (and–dare I say?–most unskeptical) and at worse downright scurrilous to leap to the conclusion that Dr. Teo is intentionally operating on inoperable brain tumors just to make money and then to funnel patients to the Burzynski Clinic, as PZ does here (and here):

Teo is an Australian surgeon who has a brilliant scheme for anyone with a bit of surgical skill and a complete lack of conscience. He performs surgery on inoperable brain tumors in kids dying of cancer, and then ships them off to the Burzynski clinic in Texas to get injected with urine and die.You’ve got to admit, marshaling the resources of a hospital, opening up a child’s skull, and diddling about with a knife inside without killing them is an amazing feat of impressive showmanship, sure to make devastated parents think something is being done worth $20-60,000 — even if there is no evidence at all that poking a glioblastoma with a pointy object offers any therapeutic benefit at all. I wouldn’t be at all surprised to learn that Teo is actually a very skilled surgeon. The problem is that brain surgery is not a panacea, and sometimes it is a totally inappropriate approach to deal with some cancers.

Or as Furious Purpose does here:

From reading the stories of those desperate parents of children with inoperable brain tumours, I must conclude that Dr Charles Teo may deliberately choose to operate on children with tumours he knows these kids will die of, because current medical science has no cure to offer them. He then removes the tumour or at least some of it for what is said to be between 20000.- and 60000.- dollars for the surgery at Prince of Wales Hospital in Sydney and the high dependency care required afterwards, and he then recommends to the parents for their child to have additional treatment with “antineoplastons” at the Burzynski clinic in Houston, Texas. Treatment that is not FDA-approved, that has not been shown in trials meeting current scientific standards to be effective, and that is given only in exchange for exorbitant sums of money, and may be refused if the money is not forthcoming.Charles Teo and Stanislaw Burzynski appear to be making money from the desperation of parents of dying children. Teo seems to be offering hope through surgery when there is none, and he then seems to be referring those same desperate folks for more false hope, and more expenses, to the Burzynski clinic in Houston.

Bullshit. Neither Furious Purpose nor PZ has anywhere near enough evidence to justify accusing Dr. Teo of something so vile and despicable.

It’s far more likely that Dr. Teo’s just an aggressive surgeon who thinks he’s doing his best for his patients by trying to remove tumors that other surgeons consider unresectable. Again, there’s a fine line between being surgically aggressive and surgically reckless, and there’s also insufficient evidence in the public record for me to judge whether Dr. Teo has crossed that line.

The second part of the accusation against Dr. Teo is a bit trickier. Is Dr. Teo funneling patients to Dr. Burzynski after having operated on them for in essence no reason? We only have two cases to go on, one of which doesn’t describe Dr. Teo as saying anything about the Burzynski Clinic or antineoplastons, the second of which quotes Dr. Teo as saying that he felt it would be a “good option” for his patient. Whether Dr. Teo suggested it or the patient’s parents latched on to the Burzynski Clinic and Dr. Teo gave his blessing is not known. From what we know, at best we can conclude that Dr. Teo’s grasp of science is not the greatest and that he’s prone to dubious science, as evidenced by his enthusiastic embrace of the “cell phones cause cancer” pseudoscience making the rounds. It’s quite possible that he’s similarly prone to being impressed by bad science and pseudoscience like that promoted by Dr. Burzynski. If that’s true, it’s bad. Very bad. However, it might not be true. We only have two cases that we know about over 8 or 9 years to go on, and Dr. Teo operates on hundreds of patients a year. These two cases could easily be outliers.

It’s clear that Dr. Teo is a controversial figure. He’s wrong on mobile phones and cancer. He also seems to have a bit more of the flamboyant showman in him than is good for a surgeon to have, a point that several of the stories I’ve cited make, and he definitely seems very cocky, perhaps more so than is necessary to be a neurosurgeon. (After all, it takes a certain amount of cockiness to have the confidence in yourself that you can crack open someone’s skull and remove part of his brain without leaving him permanently disabled.) It’s also pretty clear to me that Dr. Teo is the type of surgeon who pushes the envelope, perhaps bordering on recklessness at times. If that’s the case, he should be called out for subjecting patients to operations that can’t help them. However, I’m not convinced that that’s the case. In fact, it is not in the least bit clear to me that Dr. Teo is the sort who operates on patients whom he knows he can’t cure in order to make money, and I wish I didn’t have to point that out. When it comes to whether there’s any sort of relationship between Dr. Teo and Dr. Burzynski, I can only conclude that it’s possible–likely, even–that Dr. Teo is a bit too credulous about Burzynski’s results but that there is nowhere near enough evidence that I’ve been able to find to conclude that Dr. Teo and Dr. Burzynski have some sort of relationship in which Dr. Teo sends patients Dr. Burzynski’s way after operating on them. If there is such a relationship, then I would condemn Dr. Teo in the strongest possible terms–but I need a lot more convincing than either PZ or Furious Purpose has provided before I can come to a conclusion.

Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate

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Posted 27 Dec 2011 — by James Street
Category Cisplatin, DCA (Dichloroacetate), Mitaplatin

Shanta Dhara and Stephen J. Lipparda,b,1
aDepartment of Chemistry and bKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue,
Cambridge, MA 02139
Contributed by Stephen J. Lippard, October 29, 2009 (sent for review August 30, 2009)

The unique glycolytic metabolism of most solid tumors, known as the
Warburg effect, is associated with resistance to apoptosis that enables
cancer cells to survive. Dichloroacetate (DCA) is an anticancer
agent that can reverse the Warburg effect by inhibiting a key enzyme
in cancer cells, pyruvate dehydrogenase kinase (PDK), that is required
for the process. DCA is currently not approved for cancer treatment
in the USA. Here, we present the synthesis, characterization, and
anticancer properties of c,t,c-[Pt(NH3)2(O2CHCl2)2Cl2], mitaplatin, in
which two DCA units are appended to the axial positions of a
six-coordinate Pt(IV) center. The negative intracellular redox potential
reduces the platinum to release cisplatin, a Pt(II) compound, and two
equivalents of DCA. By a unique mechanism, mitaplatin thereby
attacks both nuclear DNA with cisplatin and mitochondria with DCA
selectively in cancer cells. The cytotoxicity of mitaplatin in a variety of
cancer cell lines equals or exceeds that of all known Pt(IV) compounds
and is comparable to that of cisplatin. Mitaplatin alters the mitochondrial
membrane potential gradient (m) of cancer cells, promoting
apoptosis by releasing cytochrome c and translocating apoptosis
inducing factor from mitochondria to the nucleus. Cisplatin formed
upon cellular reduction of mitaplatin enters the nucleus and targets
DNA to form 1,2-intrastrand d(GpG) cross-links characteristic of its
ownpotency as an anticancer drug. These properties of mitaplatin are
manifest in its ability to selectively kill cancer cells cocultured with
normal fibroblasts and to partially overcome cisplatin resistance.
Full Article Here

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