Archive for the ‘Individualized treatment’ Category

New Patent Promises to Accelerate Cancer Trials

Comments Off
Posted 21 Feb 2012 — by James Street
Category Clinical Trials, Individualized treatment, Moffitt Cancer Center, Personalized, Targeted Cancer Therapy

Computer system IDs suitable patients, helps new drugs reach market faster

TAMPA, Fla., Feb. 14, 2012 /PRNewswire/ – A new patent has been issued to Moffitt Cancer Center for a computerized system that efficiently selects the right patient for the right clinical trial. The newly patented system matches the registered patient’s own molecular profile – warehoused in a database of thousands of patient-donated biological tissue or tumor samples – to the molecular design of the drug aimed at targeting their disease at the molecular level, and do it quickly. The system promises to accelerate clinical trials and help shorten the time that it takes to get critically needed new drugs into the market.

Getting new drugs to market to fight cancer and other serious diseases requires, on average, 15 years. The drug development process is long and complex, but the three-phase clinical trials process – estimated to take up to half of those 15 years – is often the bottleneck in getting innovative drugs to the patients who need them.

Clinical trials, increasingly becoming more expensive, are also multifaceted. While patients may qualify for a clinical trial based on their age or stage of disease, they may not be, over the long term of the trial, the best candidates to test a drug. Adverse events, changes in a patient’s health status and the potential for a drug not being effective for them slow the process. Although patients may have met the trial protocol’s criteria, the drug may not be right for them because their molecular profile is not a good match for the chemical and molecular properties of the drug.

Because the concept of personalized medicine is selecting the right drug for the right patient, innovations have been needed to bring personalized medicine to reality. Personalizing the selection process for clinical trials is a vital step.

With the development of new and better ways to examine and understand a tumor’s molecular profile, matching the right patient to the right clinical trial becomes increasingly important. But handling the massive data evaluation necessary to accomplish this has been a stumbling block.

The newly patented computer system, Patent Number US 8,095,389 B2, or “Computer Systems and Methods for Selecting Patients for Clinical Trials,” is designed to surmount that problem.

The newly patented computer system is designed to:

  • Select patients to clinical trials matching an individual’s/drug’s molecular profile
  • Match patients to clinical trials by a patient’s disease/diagnosis
  • Match patients to clinical trials by their symptoms
  • Match patients to clinical trials by their demographic information and family history
  • Track a clinical trial participant’s disease progression compared to drug efficacy

The newly patented computer system and associated products, such as operating system, software, interfaces and data retrieval system, improve clinical trial selection efficacy by making the patient selection process less random and more selective. The technology has the potential to refine clinical trials by eliminating bottlenecks, overhauling the selection process and shortening the timeline, ultimately bringing new drugs to market more efficiently.

About Moffitt Cancer Center

Follow Moffitt on Facebook: www.facebook.com/MoffittCancerCenter
Follow Moffitt on Twitter: @MoffittNews
Follow Moffitt on YouTube: MoffittNews

Located in Tampa, Moffitt Cancer Center is a National Cancer Institute-designated Comprehensive Cancer Center, a description that recognizes Moffitt’s excellence in research and contributions to clinical trials, prevention and cancer control. Moffitt is also a member of the National Comprehensive Cancer Network, a prestigious alliance of the country’s leading cancer centers, and is listed in U.S. News & World Report as one of “America’s Best Hospitals” for cancer.

Media release by Florida Science Communications: www.sciencescribe.net.

SOURCE Moffitt Cancer Center

Rational Therapeutics: Intelligent selection of drug combinations

Comments Off
Posted 17 Nov 2011 — by James Street
Category Drug Testing, Individualized treatment, Personalized, Rational Therapeutics, Tumor biomarkers
Dear Subscriber, BODY LICNovember marks Lung and Pancreatic Cancer Awareness month. Both these diseases typically remain undetected until the cancer has spread. With comparatively low response rates to treatment, both of these diagnoses are generally associated with unfavorable survival statistics.

With this as a backdrop, these two diseases have provided some of our most striking successes. The recent Comedy Night Fundraiser hosted by Stevens Steak & Seafood House to benefit the Vanguard Cancer Foundation provided the opportunity to invite many of our long-term survivors onto the stage for recognition and a photo opportunity.

 

As I looked about the room, I could count among the attendees, lung cancer patients, many of whom are now five or even 10 years since their original diagnoses. Those who are not in the field of medical oncology might not be familiar with the survival statistics for this disease, but I assure you that the words “long-term” and “survivorship” are rarely found in the same sentence as lung cancer.

 

BODY LIC

Dr. Nagourney with some of the long-term lung cancer survivors in attendance at the “Laughter is Contagious” event.

 

While advances in this disease include the discovery of genetic targets for the newest agents like erlotinib (Tarceva) and crizotinib (Xalkori), many of the patients joining us that evening have benefited from more conventional chemotherapy drugs. This only further reinforces our belief that the intelligent selection of therapy can improve outcomes, even without the addition of new classes of therapeutics.

 

Good outcomes in cancer do not necessarily reflect the addition of a new drug or combination, but instead, what can occur simply through the intelligent application of available diagnostic, therapeutic and supportive measures towards the greatest good for each patient.

 

Our provision of assay-directed therapy represents an important step forward in the use of anti-cancer drugs. As we continue to confront hurdles in providing these services to the largest number of patients possible, the support and sponsorship of the Vanguard Cancer Foundation remains an integral part of our mission. With our ongoing efforts to develop the next generation of effective therapies, we look forward to providing our discoveries to patients, regardless of their ability to pay.

 

We look forward to a new year, and to continuing our mission of “Hope Practiced Here.”

Dr. Nagourney Signature
Dr. Robert Nagourney
Rational Therapeutics

New analytical method enhances the possibility of selecting optimal cancer treatment

Comments Off
Posted 12 Nov 2011 — by James Street
Category Colon Cancer, genetic research, Individualized treatment, Personalized, Tumor biomarkers

For a cancer treatment to be adapted to each individual patient, a large number of tumor samples need to be examined carefully.

Collaboration between a company and Uppsala University has now led to a method that makes this process ten times more efficient than in the past.

New cancer treatments that target specific molecules in the tumor are under development. But for this to be effective, it’s necessary to know first what mutations caused the tumor. By analyzing the sequence of genes that are often mutated in certain tumor forms, it is possible to increase the possibility of selecting optimal treatment for each patient.

Researchers at the Department of Immunology, Genetics, and Pathology at Uppsala University are collaborating with the company Halo Genomics in a project designed to identify mutations that cause cancer of the large intestine. The scientists selected 560 genes in 192 tumor samples, and Halo Genomics produced a so-called HaloPlex™ PCR-analysis that covered all the genes.

– With this analytical method it took a week for one person to prepare the 192 samples for sequencing, without any need for special equipment. This increases productivity by a factor of up to ten compared with conventional methods, says Professor Mats Nilsson, who has directed the project.

The samples are now being sequenced at SciLifeLab in Uppsala. The researchers expect to be able to identify exactly what molecules are affected in tumor cells from individual patients.

– This will be of significance when it comes to selecting the right kind of targeted treatment for patients in the future, says Mats Nilsson. The method is promising for use in diagnostics because of its low cost and high efficiency.

Read more about SciLifeLab.

Expression Profiling Findings at 12th Annual International Congress of Human Genetics

press release

Oct. 18, 2011, 9:30 a.m. EDT

Caris Life Sciences Highlights Gene

Data Presented Shows Clinical Utility of Molecular Profiling Helping Physicians Select More Effective Therapeutic Treatments for Cancer Patients

IRVING, Texas, Oct 18, 2011 (GlobeNewswire via COMTEX) — Caris Life Sciences(TM), Inc., a leading biosciences company focused on enabling precise and personalized healthcare through the highest quality molecular profiling and blood-based diagnostic services, presented at the 12th International Congress of Human Genetics (ICHG). Caris presented clinical data that demonstrates microarray analysis is a reliable and robust method to perform gene expression profiling on routine solid tumor samples. The data provides further support for the quality and clinical utility of information generated by evidence-based molecular profiling services like Caris Target Now.

The study validated a commercially available microarray platform (Illumina whole genome DASL) with clinical tumor samples including FFPE, frozen tissues and RNA later preserved samples. Clinical laboratory findings based on gene expression profiling of 2,384 solid tumors showed that researchers were able to obtain relative gene expression profiles in patient tumor samples when compared to normal reference tissue samples. All sample types yielded quality expression profiling results with a wide variety of tumor types.

“Optimizing therapeutic selections for cancer patients using the molecular profile of their individual tumor is satisfying a large unmet need in oncology,” said Dr. Matthew J. McGinniss, Director of Molecular Diagnostics and lead author of the study. “At Caris, we are committed to advancing the current understanding of various biomarkers and the role of molecular diagnostics in cancer therapy. We are confident that the findings presented at the ICHG conference will continue to validate the clinical utility of the Caris Target Now Service which provides patient- and tumor-specific information for physicians to use in selecting the most effective cancer therapies for each patient.”

Caris Target Now is an evidence-based molecular profiling service that associates biomarker status in a patient’s tumor sample to proven therapeutic agents associated with specific tumor markers. The biomarker/drug associations are drawn from nearly 100,000 published clinical studies that are reviewed and graded by Caris’ evidence team of PhDs. Caris Target Now then provides a consolidated report outlining a personalized list of treatment options, including those that may be more likely to elicit a response, as well as those likely to be ineffective.

About Caris Life Sciences

Caris Life Sciences, a leading biosciences company, specializes in the development and commercialization of the highest quality molecular profiling and blood-based diagnostic technologies, in the fields of oncology, dermatopathology, hematopathology, gastrointestinal pathology and urologic pathology. The company provides academic-caliber consultations for thousands of patients a day, through its industry-leading team of expert, subspecialty pathologists. Caris also offers advanced molecular analyses of patient samples through prognostic testing services and genomic, transcriptomic, and proteomic profiling to assist physicians in their treatment of cancer. Currently, Caris is developing a series of blood tests utilizing the patented Carisome(TM) platform — a proprietary, blood-based testing technology for diagnosis, prognosis, and theranosis of cancer and other complex diseases. The company is headquartered in the Dallas metroplex, and operates laboratories at the headquarters, as well as in the Phoenix and Boston metro areas.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Caris Life Sciences

        CONTACT: Caris Life Sciences
        Media Inquiries:
        Holly Clark
                    214-596-7060      
        hclark@carisls.com

EMCC Speakers Look Forward To Widespread Personalized Patient Care

By Anna Azvolinsky, PhD | September 28, 2011

 

The European Multidisciplinary Cancer Congress (EMCC), took place September 23–27 in Stockholm, brought together the European oncology community in a joint effort between the European Society for Medical Oncology (ESMO), the European Cancer Organisation (ECCO), and the European Society for Therapeutic Radiology and Oncology (ESTRO).

The multidisciplinary nature of the meeting is highlighted by the tagline of the congress—“Integrating basic and translational science, surgery, radiotherapy, medical oncology and care”—and, indeed, the meeting has emphasized the integration of these components and their important roles in driving cancer research toward providing better patient treatment and care. As clinical practice is becoming increasingly interdisciplinary with patients being treated in multidisciplinary teams, a multifaceted meeting such as this one is important for the continued dialogue, education, and communication among cancer clinicians and researchers.

The EMCC had 285 sessions and over 2,000 presentations from 707 experts in the field, with over 16,000 attendees from around the world.

A call to drive better personalized care deliverables for patients

The opening session of the EMCC emphasized that the field of oncology should continue to strive torward streamlined and personalized patient care. José Baselga, MD, PhD, the associate director and chair in hematology/oncology at the Massachusetts General Hospital Cancer Center gave a presentation, “New World of Cancer: Personalized Medicine for All Patients” that urged the cancer community to see molecular targeting of cancer as a new era. Dr. Baselga pointed out that he believes that classic approaches to cancer therapy such as radiation therapy and chemotherapy have achieved a plateau in terms of patient response. In this “classic therapy” era, only an empirical approach to clinical trial design was possible, where patient populations were unselected and large-scale trials were necessary in order to see any treatment benefit. These types of trials led to a high failure rate and minimal benefits. “The system can no longer tolerate an incremental benefit,” he stated as he transitioned to a discussion of what he calls the “new era of molecular targeting of cancer.”

As researchers and clinicians are beginning to understand the wiring of cancer and the underlying molecular causes, Baselga stated, “we are getting into an era of the right drug for the right tumor.” He went on to highlight that identifying the right molecular targets can result in the creation of specific molecules that act on these targets, and said, “chemistry is on our side, to design new treatments.” Dr. Baselga cited early success stories of targeted therapies that have resulted in dramatic patient benefits, including gefitinib (Iressa) and erlotinib (Tarceva), two selective inhibitors of EGFR for lung cancer, crizotinib (Xalkori) for lung cancer patients, which inhibits ALK in patients that harbor the EML4-ALK fusion; and vemurafenib (Zelboraf), the BRAF inhibitor that has recently been approved for metastatic melanoma.

“We will have an incremental number of genetic mutations identified in tumors and we will have an increased number of therapies to treat these tumors,” Baselga said, highlighting his optimism in the collaboration of bench-scientists and clinicians to develop new treatments, in conjunction with the increasing understanding of cancer mutations from patient tumor data.

“We have to realize that this is a watershed moment in cancer history. We have to make sure we match each drug with each individual tumor and we have to change the way we test these new drugs,” said Dr. Baselga.

Looking forward, Dr. Baselga spoke about the need for better, streamlined, and throughput methods to test these new agents for efficacy in a rational way that will provide meaningful data. After isolating compounds that have the potential to be efficacious, the ability to identify patients that will benefit is crucial. Baselga stated, “We have to embark on a comprehensive genetic characterization of tumors: chrosomomsal alterations, epigenetics, mutations, and proteomics.”

While the challenging tasks of platform and clinical validation, archiving quality specimens, improving turnaround time and informatics approaches, and looking for novel mutations is daunting, it is “far less than treating patients with expensive drugs that may not work unless they are targeted for the patient.” In this sense, the field has progressed significantly over the last decade, with the mutational landscapes for lung and breast cancers providing a categorization of subclassifications of these disease that facilitate tailored therapy treatments.

Baselga pointed out that one highly important point that, thus far, has not been widespread due to high cost and the inability to obtain appropriate patient sampling, is the serial monitoring of tumors during therapy. Looking at the genetic makeup of a tumor prior to and post-treatment will greatly facilitate the knowledge about how tumor genetic factors influence treatment response and resistance. Baselga cited the new research on circulating tumor cells (CTCs), and said that by applying novel therapies earlier in disease “you can identify very early on when a patient responds, which can help clinicians modulate therapy.”

He highlighted a particular example of the use of technology to predict response that was subsequently presented at EMCC (Gamez et al. “FDG-PET/CT for Early Prediction of Response to Neoadjuvant Lapatinib, Trastuzumab, and Their Combination in HER2-positive Breast Cancer Patients: the Neo-ALTTO Study Results, abstract #5013).

Dr. Baselga ended by listing his vision of novel clinical trial design in the new molecular era: 1) smaller smarter clinical trials without the need for 1000+ , expensive trials, 2) the importance of combination treatments 3) applying novel targeted agents earlier in the course of disease, and 4) the study of resistance to therapies. “Over the course of the next ten years,” he said, “we need good biomarker programs and facilities, the sharing of data, attracting the best pool of physician scientists into our culture of teamwork, and we need creativity and willingness in our clinical trial design.”

A pragmatic assessment of today’s personalized molecular medicine

Following Dr. Baselga’s talk, Gordon B. Mills, MD, PhD and chairman of the department of systems biology at the M.D. Anderson Cancer Center addressed what the cancer community needs to be doing to deliver personalized medicine outside of the research environment. “We have to determine to work with medicine and industry in a better manner. Drugs coming out of the pipeline must be linked to the right patient,” he stated.

Professor Mills defined personalized medicine as “the right treatment for the right person at the right and first time,” in contrast to the current practice of “trial and error.” He asked the audience to think about whether they are educating patients and physicians enough and whether they are overpromising on what the current treatments and care can deliver.

In the view of Professor Mills, there are still only subpopulations of patients that experience the biomarker benefit, calling the current phase “stratified and precision medicine.” He stated that he agreed with Dr. Baselga that breast cancer is leading the way in this. “Breast cancer is now a series of different diseases, at least eight of them. But the problem is that some of these subpopulations are too small to have clinical trials that will show good enough data. Rather than distinct diseases, currently, there are still only subpopulations,” he asserted.

Emphasizing that despite the latest positive results with targeted agents, “every single patient on [vemurafenib] has recurred.” His goal was for the oncology community to aim for higher achievements.

Finally, Professor Mills outlined the current landscape of challenges he sees that need to be overcome. In terms of patients, these include the need to identify a patient’s genetic makeup to determine whether a treatment will succeed, the need to assess individualized dosing and toxicity limits, and the issue of intra-tumoral heterogeneity and the evolution of the tumor from primary to recurrent stages of cancer.

As far as technology challenges, filtering passenger vs driver mutations is necessary, and Mills also cited the need to find actionable aberrations, as there are still a limited number of drugs for all of the mutations identified in tumors. He highlighted the fact that most tumor suppressors are still recalcitrant to treatments and that the cost of treatments is continually on the rise.

The issue of the accrual of large amounts of sequencing information is such that database storage costs outweigh the costs of generating sequencing data, and said that this is something that needs to be addressed. “The $1000 genome is now the $100,000 analysis cost,” he said. Lastly, he pointed to the expanded number of parties that are involved in treatment development and implementation. He stated that the ethics of telling patients about germ-line mutations that are discovered during genomic sequencing needs to be discussed thoroughly, and mentioned the need for participation by the U.S. Food and Drug Administration in the education of patients and physicians and the issue of reimbursement for testing and sequencing.

The communication, education, and open dialogue about these issues going forward among the global oncology community and other key stakeholders, as well as about novel treatment paradigms and progress, will be highly important for oncologists to be fully entrenched in this promising molecular therapy era.

At OHSU, making treatment for breast cancer as individual as the disease with gene therapy

Comments Off
Posted 11 Sep 2011 — by James Street
Category Bioinformatics, Breast Cancer, genetic research, Individualized treatment, Personalized
Published: Saturday, September 10, 2011, 1:00 PM
By Joe Rojas-Burke, The Oregonian
joegray.JPGView full sizeMotoya Nakamura, The OregonianJoe W. Gray, a professor at Oregon Health & Science University’s Knight Cancer Institute, is known for his work tracking changes in cancer gene activity.

Doctors have many chemotherapy agents to shrink breast tumors or get rid of cancer cells left behind after surgery. Dozens more are under development. But choosing which drugs to use in a particular patient remains largely a matter of trial and error. Doctors prescribe one combination and if it doesn’t work they switch to a different set. It’s impossible to predict which regimen will work.

Joe W. Gray, a professor at Oregon Health & Science University’s Knight Cancer Institute, is known for his work tracking changes in cancer gene activity and figuring out how the changes affect the way patients respond to treatment. He’s confident that in the near future doctors will be able to order a laboratory test — based on bits of cancer tissue removed by a needle — that will reveal each cancer’s particular weaknesses. Gray’s lab and others are developing ways to rapidly scan the DNA of cancer cells to identify hundreds or thousands of genetic changes that drive tumor growth. Gray talked to The Oregonian about the prospects for using this “personalized” approach to direct cancer therapy.

 Why is it important to be able to predict how a woman with breast cancer will respond to treatment?

The last time I looked, there were over 850 therapies being developed for the treatment of various kinds of cancer, and well over 100 for breast cancer. But most of the drugs we have aren’t effective in all of the patients that receive them. They are effective in some, not in others. We’d like to be able to identify in advance which drugs will be effective, and avoid giving patients treatments that are not. We have this great armamentarium of drugs; what we need are the tools to target them to the patient populations that will best respond.

What are the genetic changes in cancer cells that define their vulnerability and resistance to different drugs?  

In cancer cells, DNA becomes unstable. It rearranges itself. Chromosomes break. Genes get spliced together abnormally. Some regions of the genome get amplified — you get more and more copies of certain genes. You get mutations turning genes off or on. They add up in an ensemble to a very complex cancer genome. There may be hundreds if not thousands of genes that have been deranged. So that’s pretty daunting. I’ve probably analyzed thousands of breast cancers. If you get down to the nitty gritty details, I’ve never seen two that are the same.

What kind of experiments are you doing at OHSU?

We’ve got about 60 different cancer cell lines that grow in the laboratory. These cancers represent several of the subtypes that we think are important. Instead of treating patients with all of the experimental drugs and drug combinations, we can treat the cell lines. Using computers, we can ask the question: What are the molecular features in the cell lines that seem to be associated with either response or resistance? Then we can go into the patient population and test the hypothesis that comes out of cancers tested in the laboratory. If you think about it, we have these hundreds of therapeutic agents that might be useful, but we just don’t have enough patients to test them all either singly or in combination. The only way you can do that is with these laboratory models. We’re just submitting a paper now that analyzes results on 77 compounds where we’ve been able to develop what we think may be useful clinical predictors for about a third of them.

Are you developing diagnostic tests for the big, multi-center trial known as I-SPY 2? OHSU is one of the 15 participating cancer centers named so far by the consortium of government and industry sponsors.

All of the drugs in the I-SPY trial will be tested in the laboratory model we have developed. We think, over the next two or three years, we will get a very good understanding of the extent that these cell lines either do or do not tell the truth. We will come up with what we think are the best predictors of response. The same tests that we run on cell lines will be run on biopsies from patients. We will ask the question: Did they predict what we saw clinically? We’re not so confident about the markers that we would use those to select treatments for patients in the clinical trial. It’s premature for that.

How soon will this sophisticated profiling be offered widely to women with breast cancer, not just in clinical trials?

There are simple versions of this being used now. There are a couple of diagnostic tests on the market that tell you whether a breast cancer patient will benefit from chemotherapy treatment at all. Both of those identify subpopulations of patients who are going to do so well that it’s probably not appropriate to treat them with chemotherapy. More complicated signatures will start proving out in the next two or three years.

What are the biggest hurdles to get over?

The therapies we have are reasonably effective, so we face a bit of an ethical dilemma. Until we really understand in-depth who is and isn’t going to respond to an experimental treatment we almost have to try the old therapies first. A lot of the molecular analysis techniques are very experimental. Many of these have only been invented in the last two or three years. It’s a balance between moving medicine forward and being as absolutely sure as we can that we don’t do any harm to the patient.

What are the practical hurdles?

Imagine the physician and patient being given a molecular profile composed of a million measurements. And you’ve got hundreds of drugs from which to choose. There’s a huge amount of information to ingest. What do you do with that? It will be important to develop computational tools that bring in everything we know about cancer drugs and everything we know about predictions of drug response based on molecular profiles and provide decision support to help you manage and interpret the data. We’re getting to the point where this is complicated enough that the unaided human can’t do it.

What makes you confident this will work?

You have to trust biology on this. Biology is telling us that different cancers arise from different mechanisms, and because they arise from different mechanisms, they are susceptible to different drugs. We know from a wealth of evidence that that is a fundamental truth. It has not been until recently we’ve been able to measure enough about cancers to be able to understand the mechanistic differences that influence response to therapy. It’s something that’s come into reality in the last two or three years. That science is still emerging, so it’s going to take a while. The war on cancer was initiated by President Nixon in 1971, about 40 years ago. Since then we have learned an enormous amount about the mechanisms by which tumors arise and that influence response to therapies. We have a growing number of new therapies that we can consider using. And we finally are getting the tools we need to begin to understand how to match the therapies to individual tumors. But you still have to take the baby steps that are needed to put all of this together to reach the ultimate goal of more effective and durable cancer treatment.

Joe Rojas-Burke

Close Call – A Physician’s Personal Encounter With Cancer

Comments Off
Posted 24 Aug 2011 — by James Street
Category Individualized treatment, Personalized, Physicians, Rational Therapeutics, Tumor biomarkers

There are some things we can only experience for ourselves.

Very few who have not had cancer would believe how little is known about treatment and how ineffective most of it is. As this becomes evident, we are dying. It is too late for most.

In my case, my chest was ravaged by metastatic kidney cancer. My red blood cells were mysteriously gone, while the chemotherapy I had obediently taken for three months had done nothing. I was not expected to live.

Good fortune led me to Robert Nagourney, MD, an oncologist who does chemosensitivity testing on samples of patients’ tumors. Just in the nick of time I made a “pilgrimage” to his office in Long Beach, California. The test, or “functional profile” of my tumor, led to a recommendation for a combination of three conventional anti-cancer drugs. However, none are drugs of choice for kidney cancer; none of them would have been used as “standard” therapy.

Within two weeks, my chest x-ray was clearing and my blood count was improving. I was feeling better. Five months after diagnosis and two months on the new treatment, my chest metastases were “melting away.”

I had no assurance that the army of kidney cancer cells wouldn’t be coming back tomorrow.  I may have been living on borrowed time. So I chose to use it to begin telling my story.

Because even though I’m a physician, I suspect my encounter with cancer is not that different from the experience of others.

Except, perhaps, for the outcome.

John FreidbergTwo months ago, I underwent a nephrectomy/tumorectomy (consisting of a six hour procedure to remove my huge tumor and right kidney). Followed by one week of recovery.  Two weeks ago, on July 2011, my follow-up CT/PET was entirely negative – tumor gone, nodes gone, chest clear. It put a smile on everyone’s face: the surgeon, my local oncologist Gary Cecchi, MD, the oncology nurses and me, of course.

It’s hard to believe that one year ago, I was on the brink of death with a diagnosis of Stage 4 renal cell cancer, a diagnosis carrying a 5 percent chance of a 5-year survival. Dr. Cecchi, has now declared me “in remission.” I’m almost back to normal, building muscles back, swimming and even taking an Aikido Martial Arts class.

The public needs to know about the chemosensitivity tests I had and about the handful of physicians, like Dr. Nagourney, who are saving lives with personalized cancer therapy every day.

My story is here to give hope to patients who are almost certainly demoralized by the conventional attitudes toward renal clear cell carcinoma: chemo doesn’t work!? When it’s done right it does. And Dr. Nagourney made sure it was done right on me.

Read more about Dr. Freidberg and others patients, in their own words, on the

Rational Therapeutics website.

 

Rational Therapeutics, Dr. Robert Nagourney

Comments Off
Posted 24 Aug 2011 — by James Street
Category experimental treatments, Individualized treatment, Personalized, Physicians, Tumor biomarkers

As we prepare this edition of our newsletter we are pleased to report that our Phase II clinical trial in advanced lung cancer has been submitted and is under review for publication.

As the field of laboratory-directed therapies has confronted resistance from investigators who call for controlled clinical trials to validate this approach, it is important to continue providing prospective documentation of the efficacy and clinical utility of assay-directed therapy. While there are many excellent retrospective analyses constituting almost 2,000 patients, directed trials that use assay selection for the upfront choice of chemotherapy are more compelling yet fewer in number.

It is with a sense of satisfaction and accomplishment that we submit this study in which previously untreated patients with metastatic lung cancer received assay-directed therapy selected from among drugs that are FDA approved, commercially available and in wide use for this disease.

In our report, we succeeded in doubling the response rate from an historical experience of 30 percent to 64 percent and achieved strong statistical significance (p=. 00015). In addition, the median survival for patients in our study of 21.3 months nearly doubled the best available results in the literature of 12.5 months. As several of our patients remain alive close to seven years at this writing, we believe that this approach to therapy has the capacity to alter the natural history of lung cancer – the leading cause of cancer death in America.

The results of our lung cancer study, in which only conventional chemotherapeutics were used, strongly supports our belief that this laboratory platform could offer even greater opportunities to streamline the introduction of the newest classes of targeted agents. We have initiated discussions with a pharmaceutical firm to implement directed studies with some of the newest signal inhibitors. It is our hope that patients with refractory malignancies, those who may not benefit from conventional therapies, will soon be able to avail themselves of these new classes of targeted agents based upon laboratory selection, all under the auspices of IRB approved protocols. (IRB is the acronym for Institutional Review Board for Human Participants. Any institution that receives federal funding to conduct research is required to establish an IRB to review investigations which directly or indirectly involve human participants.)

It is important to remember that new drugs aren’t always better drugs. In this context, the remarkable success of one our kidney cancer patients who had shown no response to the newest targeted VEGF inhibitors, has now achieved a complete remission using assay-directed  conventional cytotoxics, represents the advantage of drug selection over the random introduction of new drugs. His normal PET/CT scan is a monumental success for directed therapies and reaffirms the dictum at Rational Therapeutics that all patients should receive “whatever works best.”

Dr. Nagourney Signature
Dr. Robert Nagourney
Rational Therapeutics

P.S. Last month I was honored to present at the TedXSoCal conference here in Long Beach, California. It was a most rewarding experience. You can view the video on You Tube.

Genetic differences distinguish stomach cancers, treatment response

Contact: Sarah Avery
sarah.avery@duke.edu
919-660-1306
Duke University Medical Center

SINGAPORE – Stomach cancer is actually two distinct disease variations based on its genetic makeup, and each responds differently to chemotherapy, according to an international team of scientists led by researchers at Duke-National University of Singapore Graduate Medical School.

The finding, published in the Aug. 1, 2011, edition of the journal Gastroenterology, is the first large-scale genomic analysis of gastric cancer to confirm the two discrete tumor types.

The researchers also found that a certain regimen of chemotherapy is more effective on one tumor type, while a different drug works best on the other, setting the groundwork for a more effective approach to treating gastric cancer patients.

“Our study is the first to show that a proposed molecular classification of gastric cancer can identify genomic subtypes that respond differently to therapies, which is crucial in efforts to customize treatments for patients,” said Patrick Tan, M.D., PhD, senior author of the study and associate professor in the Cancer and Stem Cell Biology Program at the Duke-NUS Graduate Medical School.

An estimated 21,000 people in the United States will be diagnosed with stomach cancer this year, and 10,570 will die of the disease, according to the National Cancer Institute. Worldwide, only lung cancer is more lethal.

Patients have long had markedly different responses to treatments, suggesting that their tumors may have underlying differences.

Hinting at those differences, a microscopic pathology test developed in the 1960s broadly described how well the tumor cells clumped together, typing them as either “intestinal” or “diffuse.” Known as the Lauren classification, after the doctor who first described the distinctions, the analysis fell short as a reliable prognostic tool.

“Most gastric cancer patients today are still being treated with a common one-size-fits-all regimen,” said Tan, who also serves as group leader at the Genome Institute of Singapore and a senior investigator at the Cancer Sciences Institute of Singapore.

“One reason for this is that the Lauren classification requires significant gastric cancer experience and there is considerable variation in classifying gastric cancers, even among qualified pathologists,” Tan said.

But the genetic findings by the Singapore-based researchers add greater specificity to the microscopic classifications and, for the first time, provide some guidance for doctors to prescribe effective treatments.

The team first analyzed 37 gastric cancer cell lines, which were pure cancer cells free of blood, tissue and other adulterations that could skew results.

Gene expression profiles yielded highly distinct patterns that indicated the two subtypes. In 64 percent of cases, the genetic subtypes validated the Lauren classifications – either intestinal or diffuse. In the other 36 percent of cases, the genomic process distinguished the subtypes where the pathology test could not.

Findings were confirmed using tumor samples from 521 cancer patients.

“It was quite reassuring to us that the genomic subtypes were associated with Lauren’s system,” Tan said. “There is a general assumption in the field that intestinal and diffuse gastric cancers (as classified by Lauren) represent two very different versions of gastric cancer, and now genomic data confirms this by demonstrating that the two genomic subtypes have very different molecular patterns.”

Establishing the highly accurate definition of tumor subtypes enabled the researchers to observe the different responses to chemotherapy. The intestinal-type tumors showed significantly better response to the chemotherapies 5-fluorouracil and oxaliplatin, and were more resistant to cisplatin than the diffuse tumors.

“The exact mechanistic reasons for this difference are currently unclear, and this is an area that we are actively working on,” Tan said, adding that the researchers are working to find subtype-specific molecular vulnerabilities to drugs.

The researchers have launched a prospective clinical trial, called the 3G study, where gastric cancer tumors will be genomically profiled, and treatments will be allocated on the basis of the tumor type.

###

In addition to Duke-NUS, research institutions included the National Cancer Centre Singapore; National University of Singapore; Singapore General Hospital; Genome Institute of Singapore; Yonsei Cancer Center, Seoul, South Korea; Peter MacCallum Cancer Centre, East Melbourne, Australia; National University Health System, Singapore; Kanagawa Cancer Center, Yokohama, Japan; Leeds Institute for Molecular Medicine, Leeds, England; Yonsei University College of Medicine, Seoul, South Korea; MD Anderson Cancer Center, Houston, Texas.

The study was funded by the Biomedical Research Council and National Medical Research Council of Singapore, Duke-NUS Graduate Medical School, and the Cancer Sciences Institute of Singapore. The researchers reported no conflicts of interest.

New Genetic Mutations Found for Non-Hodgkin Lymphoma

Dr. Lisa RimszaDr. Lisa Rimsza

By Sara Hammond, Arizona Cancer Center, July 27, 2011

Some tumor samples for the cancer-sequencing study came from the Arizona Lymphoma Repository housed in the UA College of Medicine.

 

Scientists at the BC Cancer Agency in British Columbia, Canada and their U.S. collaborators have identified a number of new genetic mutations involved in non-Hodgkin lymphoma, or NHL.

This massive cancer-sequencing study, published online in the journal Nature, will open a floodgate for researchers around the world to explore the significant number of newly discovered gene mutations and their role in the growth and development of lymphoma cells.

The work was performed at the BC Cancer Agency Genome Sciences Centre, which has received major support from several governmental and private sources, including the U.S. National Institutes of Health in Bethesda, Md.

In an extensive undertaking, researchers sequenced the entire genome of lymphoma cancer cells from 14 NHL patient samples and the “active” genes from 117 NHL patients to search for genetic mutations specific to cancer cells.

Tumor samples were collected from British Columbia scientists as well as their U.S. collaborators, including the Arizona Lymphoma Repository housed at the University of Arizona’s College of Medicine under the direction of Dr. Lisa Rimsza, a professor of pathology and Arizona Cancer Center member.

The magnitude of data revealed 109 genes with recurring mutations, from which 26 have been identified as contributors to NHL based on their mutation patterns. More than two-thirds of mutated genes had never been linked to lymphoma prior to this study.

Understanding tumors’ genetic signatures “tells us what makes the tumors tick and what might be their vulnerable spots to aim for with treatment. This information should provide better diagnoses, more accurate prognostic information and help to identify unique targets of therapy for each tumor type, therefore advancing personalized medicine for our patients,” Rimsza said.

“Based on the patterns of mutation in these 26 genes, we can see that these mutations enable tumor cells to grow and expand in non-Hodgkin lymphoma patients,” said Ryan Morin, the study’s lead author. “The mutated genes we’ve discovered, most of which were previously unknown to lymphoma or other cancers, should enable us to design new tests that allow us to recognize subtypes of lymphoma and may help us predict how each variation of this disease will react to different treatments.”

Non-Hodgkin lymphoma is the fifth most common form of cancer in Canada, and the fourth most common cause of cancer in the U.S.

“This new abundance of genetic information is thrilling. Researchers and clinicians can now collaborate to eventually create new drugs, or identify existing drugs, that inhibit these mutated genes directly and prevent the growth of non-Hodgkin lymphoma,” said Dr. Joseph Connors, a medical oncologist and distinguished scientist at the BC Cancer Agency and a clinical professor of medical oncology at the University of British Columbia.

The pattern of mutation observed in some of these genes is indicative of new tumor suppressors and oncogenes, the latter of which may be ideal targets for existing therapies.

Specifically, one of the novel lymphoma-related genes discovered in this study, MLL2, is mutated in 89 percent of Follicular lymphoma patients, suggesting it is the most commonly mutated gene in NHL. Mutation of MLL2, which appears to be a tumor suppressor, is suspected to provide cancer cells with the ability to grow rapidly in-spite of the body’s regulatory mechanisms.

A second novel gene discovery, MEF2B, bears a so-called “hot spot” mutation pattern reminiscent of other known cancer genes.