Archive for the ‘Ovarian’ Category

Chemo drug drives growth of some tumors

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Posted 31 Jan 2012 — by James Street
Category Adriamycin, doxorubicin, Ovarian, Stem Cell Research
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Ovarian cancer stem cells stimulated by common treatment
Web edition : Monday, January 23rd, 2012
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Chemotherapy drugs designed to kill tumors may actually encourage ovarian cancer by stimulating the growth of cells that give rise to the malignancy, a new study finds.

“It was quite a surprise, actually, that chemotherapy could stimulate growth,” says Kenneth Nephew, a cancer biologist at the Indiana University School of Medicine in Bloomington, who was not involved in the new work. “When clinicians see this paper it may raise a few eyebrows.”

Researchers led by Patricia Donahoe and Xiaolong Wei of Massachusetts General Hospital and Harvard Medical School found that the common chemotherapy agent doxorubicin actually encourages the growth of ovarian cancer stem cells. The immature cells make up less than 1 percent of an ovarian cancer, but just a few left behind after surgery can reestablish a tumor.

But the study, published online the week of January 23 in the Proceedings of the National Academy of Sciences, also offers hope. The researchers found that a protein called Müllerian inhibiting substance, or MIS, halts growth of cancer stem cells. Made by male fetuses and boys until puberty, the protein reverses the growth of tissues that would otherwise develop into fallopian tubes.

MIS treatment might be combined with chemotherapy (which does kill most mature ovarian cancer cells) to stop growth of all the cancer cells, says Charles Landen, a gynecologic oncologist at the University of Alabama at Birmingham. Since humans naturally produce the potential anti-stem cell treatment, it would probably be safe to use in a clinical setting, he says.

Such therapy is still a long way off, says Donahoe. The researchers are able to produce only enough Müllerian inhibiting substance for use in a laboratory setting. Making enough of the protein to test in clinical trials will probably require a commercial partner.

Other researchers have identified different types of ovarian cancer stem cells, but Donahoe and her colleagues “have defined what may be the most aggressive subset of tumor cells,” says Landen.

It’s not clear if the MIS protein can stop all types of ovarian cancer stem cells.

New Spray Lights up Cancer Cells During Surgery

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Posted 24 Nov 2011 — by James Street
Category Ovarian, Surgery
Nov 23, 2011 | 2:27 PM ET | Sarah C.P. Williams, MyHealthNewsDaily Contributor

A sprayed substance that turns fluorescent green when it hits cancer cells could revolutionize the way surgeons remove tumors.

Researchers tested the spray on ovarian tumors in mice, and it lit up the cells of all tumors that contained a specific molecule. Around 70 percent of human ovarian tumors have that marker.

“The probe doesn’t have any color before it’s sprayed onto a tumor,” said Hisataka Kobayashi of the National Cancer Institute, lead researcher on the new work. “But once it’s activated by cancer cells, it lights up and we can see it.”

The spray could show surgeons in the middle of an operation whether they’ve gotten out all the cancerous cells when they remove a tumor.

The findings were published today (Nov. 23) in the journal Science Translational Medicine.

Tool for surgeons

The cancer molecule that the spray detects is called GGT, for gamma-glutamyltranspeptidase. GGT is found in ovarian cancers as well as a fraction of other tumors, including some colon, gastric and liver cancers.

Kobayashi and his colleagues knew that GGT makes a cut in a certain protein. So the scientists engineered a fluorescent probe that lit up only when it was cut. They then formulated the probe into a spray.

When the spray lands on a tumor cell that has GGT molecules on its surface, it lights up within 10 to 20 seconds, Kobayashi said. Even if there are only a few sparse molecules of GGT, the spray will fluoresce within two minutes.

The team tested the spray on mice with ovarian tumors. The researchers genetically engineered the mouse tumors to fluoresce red, then used the spray, which turns green. The red and green regions overlapped, showing the effectiveness of the spray.

Kobayashi noted that other methods of looking for cancer cells in people rely on formulations administered ahead of time — the night before a surgery or procedure, for example. The spray would be faster and easier.

“I think this is a very practical approach,” he said. “If you need to inject an agent ahead of time, or a night before, it’s less practical to use. But with this one, a surgeon can use it anytime they want” to see where the edges of the tumor lie.

Study in humans needed

“I thought this was great work,” said Dr. Michael Bouvet, a surgeon at the University of California, San Diego Cancer Center. “Something that allows surgeons to just spray it onto the tumor, and get a quick readout of what’s cancer and what’s not, is very appealing.”

However, Bouvet noted that the spray would be useful only for tumors known to express GGT. And more work is needed to test the safety and effectiveness of the spray in humans.

Researcher Robert Hoffman of UCSD is looking forward to the day it can be used on ovarian cancer patients.

“Ovarian cancer is a horrendous disease and it has a tendency to spread all over the ovarian cavity,” Hoffman said. “If we’re able to see it, as opposed to not see it, that’s a big advantage.”

The scientists said the spray could be applied directly into the body during a surgery, to make sure there are no cancer cells remaining. Additionally, the spray could be applied to a tumor that has been removed, to illustrate whether the margins — the borders around the tumor — are truly cancer-free.

Other approaches to detecting tumors are in the development pipeline, Bouvet and Hoffman said. One involves a fluorescent molecule that lights up in the presence of telomerase — a protein that’s more universal across cancer types. However, not all the probes act as quickly as the GGT spray.

Pass it on:  A new spray that lights up cancer cells might help surgeons detect whether they’ve removed all of a tumor.

New Preclinical Studies for NKTR-102 Presented at 2011 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer

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Posted 16 Nov 2011 — by James Street
Category Ovarian

SAN FRANCISCO, Nov. 15, 2011 /PRNewswire via COMTEX/ — Nektar Therapeutics NKTR -1.80% today presented positive preclinical data for NKTR-102, a next-generation topoisomerase I inhibitor, at the 2011 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer being held in San Francisco, California. The preclinical data demonstrates that NKTR-102 administered in combination with pegylated liposomal doxorubicin (PLD) in vivo has strong synergistic anti-cancer properties exhibiting a 100% complete response rate with no tumor re-growth in over 90% of animals. In addition, the study showed that there was no additive toxicity when combining NKTR-102 with PLD in a preclinical model of ovarian cancer.

“Results from these nonclinical studies of NKTR-102 combined with PLD and as a single agent are highly compelling,” said Robert Medve, M.D., Chief Medical Officer of Nektar Therapeutics. “In the models of platinum-resistant ovarian cancer, NKTR-102 showed synergistic anti-tumor activity with PLD. These preclinical data support the future exploration of NKTR-102 in combination with PLD in platinum-resistant ovarian cancer.”

The data presented at the 2011 AACR-NCI-EORTC meeting show that in an in vivo model of platinum-resistant human ovarian cancer, a single-dose of single-agent NKTR-102 resulted in a 100 percent complete response rate and a delay in tumor growth of up to 38 days at the highest dose. In the same model, multiple doses of single-agent PLD achieved only one partial response and a delay in tumor growth of up to only 24 days at its highest dose. NKTR-102 administered in combination with PLD showed synergistic anti-tumor activity with a 100 percent complete response rate and no tumor re-growth for 93% of the animals within a 69-day observation period.

NKTR-102 and PLD Nonclinical Data

These data were presented today at the 2011 AACR-NCI-EORTC meeting during the Topoisomerase Inhibitors session (Abstract C209) entitled “Strong synergistic activity of NKTR-102 – Pegylated Liposomal Doxorubicin (PLD) Combination Therapy in a Nonclinical Model of Platinum-Resistant A2780 Human Ovarian Cancer.” The poster presentation is also available at http://www.nektar.com/product_pipeline/oncology_nktr-102.html .

About NKTR-102

Nektar is developing NKTR-102, a next-generation topoisomerase I inhibitor with reduced peak concentrations and a continuous concentration profile. NKTR-102 was invented by Nektar using its advanced polymer conjugate technology platform, and is the first oncology product candidate to leverage Nektar’s releasable polymer technology platform.

NKTR-102 is being evaluated in multiple clinical studies. In ovarian cancer, a 71-patient Phase 2 clinical trial of NKTR-102 has been completed in patients with platinum-refractory/resistant ovarian cancer. In June 2010, the ovarian cancer Phase 2 study was expanded to evaluate single-agent NKTR-102 in women who progressed while on Doxil therapy, and this study is ongoing. In metastatic breast cancer, a 70-patient study of NKTR-102 in second- and third-line metastatic breast cancer is completed. A Phase 3 clinical trial of NKTR-102 in patients with metastatic breast cancer, the BEACON study (BrEAst Cancer Outcomes with NKTR-102) study, is planned to start in December 2011. NKTR-102 is also being tested in second-line colorectal cancer as both a single-agent and in combination with 5-fluoracil/leukovorin.

 

Fat cells in abdomen fuel spread of ovarian cancer

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Posted 31 Oct 2011 — by James Street
Category Fasting, Obesity, Ovarian

Contact: John Easton
john.easton@uchospitals.edu
773-795-5225
University of Chicago Medical Center

Similar process may boost growth of other cancers

IMAGE: This is Ernst Lengyel, MD, PhD, professor of obstetrics & gynecology, the University of Chicago.

Click here for more information.

A large pad of fat cells that extends from the stomach and covers the intestines provides nutrients that promote the spread and growth of ovarian cancer, reports a research team based at the University of Chicago in the journal Nature Medicine, published online October 30th, 2011.

Ovarian cancer, the fifth leading cause of cancer deaths in women, tends to spread within the abdominal cavity as opposed to distant organs. In 80 percent of women, by the time ovarian cancer is diagnosed, it has spread to the pad of fat cells, called the omentum. Often, cancer growth in the omentum exceeds the growth of the original ovarian cancer.

“This fatty tissue, which is extraordinarily rich in energy-dense lipids, acts as a launching pad and energy source for the likely lethal spread of ovarian cancer,” said study author Ernst Lengyel, MD, PhD, professor of obstetrics and gynecology at the University of Chicago. “The cells that make up the omentum contain the biological equivalent of jet fuel. They feed the cancer cells, enabling them to multiply rapidly. Gaining a better understanding of this process could help us learn how to disrupt it.”

The researchers performed a series of experiments to identify the role of these fat cells as major mediators of ovarian cancer metastasis. The first step was to understand the biological signals that attract ovarian cancer cells to the omentum and use it for rapid growth.

The spread of ovarian cancer cells to the omentum can happen quickly. Ovarian cancer cells injected into the abdomen of healthy mice find their way to the omentum within 20 minutes. The researchers found that protein signals emitted by the omentum can attract the tumor cells. Inhibitors which disturbed these signals reduced this attraction by at least 50 percent.

Once ovarian cancer cells reach the omentum, they quickly develop the tools to devour the sustenance provided by this fatty tissue, reprogramming their metabolism to thrive on lipids acquired from fat cells. Ovarian cancer can rapidly convert the entire omentum, a soft fat pad, into a solid mass of cancer cells.

“This mechanism may not be limited to ovarian cancer cells,” the authors note. Fat metabolism may also contribute to cancer development in other environments where fat cells are abundant, such as breast cancer.

A protein known as fatty acid binding protein (FABP4), a fat carrier, may be crucial to this process and could be a target for treatment.

When the researchers compared primary ovarian cancer tissue with ovarian cancer tissue which had spread to the omentum, they found that tumor cells next to omental fat cells produced high levels of FABP4. Cancer cells distant from the fat cells did not produce FABP4.

When they inhibited FABP4, the transfer of nutrients from fat cells to cancer cells was drastically reduced. Inhibition of FABP4 also reduced tumor growth and the ability of tumors to generate new blood vessels.

“Therefore,” the authors wrote, “FABP4 emerges as an excellent target in the treatment of intra-abdominally disseminating tumors, which preferentially metastasize to adipose tissue such as ovarian, gastric, and colon cancers.”

###

The research was supported by the National Institutes of Health, the Burroughs Wellcome Fund, the Committee on Cancer Biology at the University of Chicago and Bears Care, the charitable beneficiary of the Chicago Bears Football Club.

Additional authors include Kristin Nieman, Hilary Kenny, Carla Penicka, Andras Ladanyi, Marion Zillhardt, Iris Romero, Diane Yamada, Rebecca Buell-Gutbrod and Katja Gwin of the University of Chicago; Mark Carey and Gordon Mills of M.D. Anderson Cancer Center; Gökhan Hotamisligil of the Harvard School of Public Health, and Marcus Peter of Northwestern University.

‘Preventive’ breast cancer surgery has some docs alarmed

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Posted 16 Oct 2011 — by James Street
Category Breast Cancer, Ethics of Science, Ovarian

By Liz Szabo, USA TODAY

Lisa Bonchek Adams was only 37, with a new baby and two older children, when her doctor noticed something strange during a routine breast exam. Although her doctor didn’t feel a lump, one breast felt “different” from the other.

A few weeks later, Adams learned that she needed a mastectomy. Follow-up tests indicated there were cancer cells throughout Adams’ left breast, dispersed too widely to be removed with a lumpectomy.

That’s when Adams made a surprising decision. She asked her surgeon to remove both of her breasts, not just the one with cancer.

A small but growing number of young women are choosing this kind of aggressive surgery, called contralateral prophylactic mastectomy. Women such as Adams say the surgery allows them to retake control of a frightening disease. But the trend has alarmed some doctors, who say such surgeries are unlikely to help the average woman or improve her survival.

“I think women feel like, ‘I’m going to go through this once, and I don’t want to go through this worry again,’” says Adams, 42, of Darien, Conn. “I wanted to do everything I could to have as much time with my children.”

Across the country, the number of breast cancer patients choosing preventive removal of the unaffected breast grew by 10 times from 1998 to 2007, when about 5% of all patients opted for the procedure, says a study published last year in Annals of Surgical Oncology.

Among young women such as Adams, rates have risen even higher, tripling since 2000, says the University of Minnesota’s Elizabeth Habermann, co-author of a 2010 study in the Journal of Clinical Oncology. In 2006, the last year for which national data are available, more than 15% of breast cancer patients ages 18 to 39 had a healthy breast removed, she says.

Individual hospitals are seeing similar trends.

At New York’s Memorial Sloan-Kettering Cancer Center, the number of women having preventive mastectomies grew from 7% in 1997 to 24% in 2005, according to an April study in the Journal of Clinical Oncology. At the University of Minnesota, a study in 2006-07 found that 29% of breast cancer patients chose to have both breasts removed, although only one was affected.

Some doctors worry that young women are undergoing unnecessary surgery. The April study from Memorial Sloan-Kettering found that most women having preventive mastectomies weren’t at high risk for relapse.

But women can’t be blamed for choosing aggressive therapy, given that doctors can’t always predict who’s at the greatest risk of dying, says Fran Visco, president of the National Breast Cancer Coalition.

Lack of progress, options

“We really haven’t made enough progress to give these women enough options,” Visco says. “We can say, ‘You are probably going to be fine,’ but we can’t say, ‘You are definitely going to be fine.’ So this drastic intervention is all we have. And that’s pretty sad, after all these years and billions of dollars spent.”

Doctors say a number of factors are driving the trend:

• Fear of relapse. A study published in this month’s Annals of Surgical Oncology shows that women with breast cancer believe they have a 31% chance of developing a new tumor in the opposite breast. The actual risk is less than 7% after 10 years, even among women thought to be at greater risk, such as those under 45 at diagnosis.

• New technology. A growing number are getting MRIs, or magnetic resonance imaging, before surgery, says Patricia Ganz, a breast specialist at UCLA’s Jonsson Comprehensive Cancer Center. MRIs sometimes find minute cancers in the other breast that are too small to see on mammograms, Ganz says. A 2009 study in Annals of Surgical Oncology found that women who had preoperative MRIs were twice as likely as others to have a preventive mastectomy.

• Genetic testing. Many young women who get aggressive surgery have mutations in genes called BRCA-1 and BRCA-2 that sharply increase their risk, Ganz says. The mutations cause 5% to 10% of breast cancers. She says she has seen a growing number of women opt for preventive mastectomies since tests became widely available in the late 1990s. In 2008, actress Christina Applegate announced she had a double mastectomy, based partly on the fact that she carries the mutations.

Ganz says aggressive surgery may be appropriate in young gene carriers, who have a 60% lifetime risk of developing another breast cancer in the opposite breast. Some of these women also opt to remove their ovaries, a surgery that also reduces their risk of future cancers.

And while studies have sometimes produced conflicting results, there’s no clear evidence that removing the healthy breast actually improves survival, even for women with the mutations, says a 2010 article in Annals of Surgical Oncology by surgeon Katharine Yao.

That’s partly because of their low overall risk and because doctors monitor cancer survivors so closely, Ganz says. Overall, a woman’s chances of survival are based more on the aggressiveness of the first tumor than the appearance of second cancers, according to Yao’s study. Only 2.5% of breast cancer deaths are a result of tumors that develop in the opposite breast, her study says.

And mastectomy isn’t the only way to reduce the risk of future cancers. In her study, Yao notes that chemotherapy and hormonal therapies also can help women stay cancer-free.

Some doctors are concerned that women overestimate the benefits of mastectomies.

For example, actress Wanda Sykes announced last month that she now has “zero chance of having breast cancer” after a double mastectomy. Sykes had the surgery after doctors discovered tumor cells called DCIS, or ductal carcinoma in situ, which doctors view as either a very early breast cancer or a precancer, in her left breast.

Mastectomy reduces the risk of cancer by 90%, but tumors can still grow back in scar tissue or under the arm, Ganz says. Sykes has said she has a family history of breast cancer but has not publicly said whether she carries genetic mutations.

‘Enormous climate of fear’

Surgeon Susan Love, author of Dr. Susan Love’s Breast Book, says doctors need to make sure that women have all the facts and don’t fall prey to “wishful thinking” about aggressive treatment. “Women think, ‘If we offer up our breasts to the gods, we will get our lives back,’” says Love.

“There is an enormous climate of fear, whether that’s from Breast Cancer Awareness Month or the news media the other 11 months of the year,” says Monica Morrow, a breast cancer specialist at Memorial Sloan-Kettering. “The only thing you ever hear about breast cancer is about some woman who’s dying because she didn’t get treated in time.”

Otis Brawley, chief medical officer at the American Cancer Society, says his organization constantly struggles with the question “How can we accurately portray the concerns about breast cancer without overly alarming people?”

Adams says she carefully weighed her options. She dreaded the thought of going through decades of mammograms, biopsies and other tests. A double mastectomy also offered cosmetic advantages, she says, allowing her plastic surgeon to make her breasts symmetrical.

No regrets about her choice

“The decision to remove the breast that was seemingly cancer-free was an easy one for me,” Adams says. “That roller coaster of emotions each time is something I didn’t want to deal with. … I was treating my cancer aggressively so that I could put some of those emotions of fear and worry behind me.”

Follow-up tests further convinced Adams that she had made the right decision: Doctors learned that her cancer was larger than they had originally realized, and it had even spread to one of her lymph nodes. Doctors also found abnormal cells in her healthy breast.

Adams also had four months of chemotherapy. Then, at age 39, she had her ovaries removed, a surgery that reduces her body’s exposure to estrogen, which can fuel breast tumors.

Five years later, Adams says she feels comfortable with her choices. Her husband also has supported her decisions. With cancer taking away so much control, Adams says, aggressive treatment allows women “to take control over something that they can control.”

Purdue technology used in first fluorescence-guided ovarian cancer surgery

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Posted 19 Sep 2011 — by James Street
Category Osteosarcoma surgery, Ovarian, Physics and Engineering, Thoracic Surgery

IMAGE: This is a surgeon’s view of ovarian cancer cells with and without the tumor-targeted fluorescent imaging agent.

Click here for more information.

WEST LAFAYETTE, Ind. – The first fluorescence-guided surgery on an ovarian cancer patient was performed using a cancer cell “homing device” and imaging agent created by a Purdue University researcher.

The surgery was one of 10 performed as part of the first phase of a clinical trial to evaluate a new technology to aid surgeons in the removal of malignant tissue from ovarian cancer patients. The method illuminates cancer cells to help surgeons identify and remove smaller tumors that could otherwise be missed.

Philip Low, the Ralph C. Corely Distinguished Professor of Chemistry who invented the technology, said surgeons were able to see clusters of cancer cells as small as one-tenth of a millimeter, as opposed to the earlier average minimal cluster size of 3 millimeters in diameter based on current methods of visual and tactile detection.

“Ovarian cancer is notoriously difficult to see, and this technique allowed surgeons to spot a tumor 30 times smaller than the smallest they could detect using standard techniques,” Low said. “By dramatically improving the detection of the cancer – by literally lighting it up – cancer removal is dramatically improved.”

The technique attaches a fluorescent imaging agent to a modified form of the vitamin folic acid, which acts as a “homing device” to seek out and attach to ovarian cancer cells. Patients are injected with the combination two hours prior to surgery and a special camera system, called a multispectral fluorescence camera, then illuminates the cancer cells and displays their location on a flat-screen monitor next to the patient during surgery.

The surgeons involved in this study reported finding an average of 34 tumor deposits using this technique, compared with an average of seven tumor deposits using visual and tactile observations alone. A paper detailing the study was published online Sunday (Sept. 18) in Nature Medicine.

Gooitzen van Dam, a professor and surgeon at the University of Groningen in The Netherlands where the surgeries took place, said the imaging system fits in well with current surgical practice.

“This system is very easy to use and fits seamlessly in the way surgeons do open and laparoscopic surgery, which is the direction most surgeries are headed in the future,” said van Dam, who is a surgeon in the division of surgical oncology and Bio-Optical Imaging Center at the University of Groningen. “I think this technology will revolutionize surgical vision. I foresee it becoming a new standard in cancer surgery in a very short time.”

Research has shown that the less cancerous tissue that remains, the easier it is for chemotherapy or immunotherapy to work, Low said.

“With ovarian cancer it is clear that the more cancer you can remove, the better the prognosis for the patient,” he said. “This is why we chose to begin with ovarian cancer. It seemed like the best place to start to make a difference in people’s lives.”

By focusing on removal of malignant tissue as opposed to evaluating patient outcome, Low dramatically reduced the amount of time the clinical trial would take to complete.

“What we are really after is a better outcome for patients, but if we had instead designed the clinical trial to evaluate the impact of fluorescence-guided surgery on life expectancy, we would have had to follow patients for years and years,” he said. “By instead evaluating if we can identify and remove more malignant tissue with the aid of fluorescence imaging, we are able to quantify the impact of this novel approach within two hours after surgery. We hope this will allow the technology to be approved for general use in a much shorter time.”

Low and his team are now making arrangements to work with the Mayo Clinic for the next phase of clinical trials.

The technology is based on Low’s discovery that folic acid, or folate, can be used like a Trojan horse to sneak an imaging agent or drug into a cancer cell. Most ovarian cancer cells require large amounts of the vitamin to grow and divide, and special receptors on the cell’s surface grab the vitamin – and whatever is linked to it – and pull it inside. Not all cancer cells express the folate receptor, and a simple test is necessary to determine if a specific patient’s cancer expresses the receptor in large enough quantities for the technique to work, he said.

IMAGE: Philip Low is pictured here in the lab.

Click here for more information.

Ovarian cancer has one of the highest rates of folate receptor expression at about 85 percent. Approximately 80 percent of endometrial, lung and kidney cancers, and 50 percent of breast and colon cancers also express the receptor, he said.

Low also is investigating targeting molecules that could be used to carry attached imaging agents or drugs to forms of cancer that do not have folate receptors.

He next plans to develop a red fluorescent imaging agent that can be seen through the skin and deep into the body. The current agent uses a green dye that had already been through the approval process to be used in patients, but cannot easily be seen when present deep in tissue. Green light uses a relatively short wavelength that limits its ability to pass through the body, whereas the longer wavelengths of a red fluorescent dye can easily be seen through tissue.

“We want to be able to see deeper into the tissue, beyond the surface,” Low said. “Different cancers have tumors with different characteristics, and some branch and wind their way deeper into tissue. We will continue to evolve this technology and make improvements that help cancer patients.”

In addition to Low and van Dam, the paper’s authors include George Themelis, Athanasios Sarantopoulos and Vasilis Ntziachristos of the Institute for Biological and Medical Imaging at the Technical University of Munich in Germany; Lucia Crane, Niels Harlaar, Rick Pleijhuis, Wendy Kelder and Johannes de Jong of the division of surgical oncology of the BioOptical Imaging Center at the University of Groningen; Henriette Arts and Ate van der Zee of the division of gynaecological oncology at the University of Groningen; and Joost Bart of the Department of Pathology and Molecular Biology of the University Medical Center of Groningen.

Low is the chief science officer for Endocyte Inc., a Purdue Research Park-based company that develops receptor-targeted therapeutics for the treatment of cancer and autoimmune diseases. Endocyte holds the license to the folate receptor-targeting technology and is spinning this technology off into a new company called OnTarget.

Ntziachristos led the team at the Technical University of Munich that developed the camera system. A startup company named SurgOptix BV is working to commercialize the camera system.

###

The clinical trial was funded by Endocyte Inc. and the University Medical Center of Groningen.

Writer: Elizabeth K. Gardner, 765-494-2081, ekgardner@purdue.edu

Sources: Philip Low, 765-494-5273, plow@purdue.edu Gooitzen van Dam, 31-50-3612283, g.m.van.dam@chir.umcg.nl

Related website: Philip Low research page: http://www.chem.purdue.edu/low/

VIDEO CAPTION:

Fluorescence-guided surgery on an ovarian cancer patient is shown.

Video is available at http://www.youtube.com/watch?v=CcUFTLVonqs

IMAGE CAPTION:

A surgeon’s view of ovarian cancer cells with and without the tumor-targeted fluorescent imaging agent. (Image courtesy of Philip Low)

A publication-quality image is available at http://news.uns.purdue.edu/images/2011/low-fluorescent.jpg

PHOTO:

Philip Low – http://news.uns.purdue.edu/images/2011/low-labshot.jpg

Abstract on the research in this release is available at: http://www.purdue.edu/newsroom/research/2011/110918LowSurgery.html

Battle Over Gene Patents Most Likely Headed to Supreme Court Posted: 8/21/11 04:13 PM ET

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Posted 21 Aug 2011 — by James Street
Category BRCA, Breast Cancer, Finance and Politics of cancer research and treatment, genetic research, Ovarian

Wake Forest University Law Professor

Posted: 8/21/11 04:13 PM ET

Courts need to be the keepers of the Constitution. But the Federal Circuit has failed its duty in the current battle over the patentability of isolated genes and gene sequences that are crucial to the fight against breast and ovarian cancer.

First some history.

The BRCA genes, which contain proteins that inhibit tumor growth, currently occupy center stage in the legal fight over the patentability of isolated genes and gene sequences.

Scientists at the University of Utah first cloned these genes after it was found that mutations in the BRCA1 and BRCA2 genes were linked to various types of breast and ovarian cancer.

Myriad Genetics is the exclusive licensee of the family of patents relating to these isolated genes and genes sequences. As a result, the company controls all sequencing of the BRCA genes as well as the diagnostic testing for the BRCA mutations.

Myriad, however, refuses to grant any licenses for second-opinion BRCA testing. The limited research licenses it has granted are severely restrictive and often prevent research scientists from disclosing the BRCA test results to their test subjects.

As a result of this restrictive licensing, the Association for Molecular Pathology, a non-profit scientific society, along with research scientists, women’s organizations and individuals, challenged the validity of the BRCA isolated gene patents in federal court on Feb. 4, 2010.

The plaintiffs argued that they were unable to access these unpatentable “products of nature” without being subject to an immediate lawsuit for patent infringement. The female plaintiffs further argued that the BRCA isolated gene and method patents gave Myriad an unconstitutional monopoly of this subject matter that prohibited them from acquiring access to life-saving information about their own genes.

In the initial ruling, the United States District Court of the Southern District of New York invalidated the isolated gene patents as patent-ineligible products of nature under the Patent Act since they were not “markedly different” from their naturally occurring counterparts, as required by the leading Supreme Court case, Diamond v. Chakrabarty.

Unfortunately, on July 29, 2011, the Federal Circuit Court of Appeals reversed the District Court. It held that the breaking of chemical bonds during the isolation process produces genetic material that constitutes “a distinct chemical entity” which is smaller and allows for the “new utility” of detecting the BRCA mutations. As such, the BRCA isolated genes and sequences are “markedly different” from the naturally occurring or “native” genes and are patent-eligible subject matter.

The majority and concurring opinions gave great weight to the Patent Office’s long-standing position that isolated genes are patentable. Judge Kimberly Moore’s concurring opinion further emphasized that to hold otherwise would be detrimental to the biotechnology industry that has relied on gene patenting — 20 percent of the human genome is currently patented — to fund continued genomic research and development.

As a former registered Patent Attorney, one question immediately came to mind after reading the Federal Circuit’s majority and concurring opinions.

How can the court allow chemical differences to supersede biological equivalence when the specific utility of the invention, namely detecting mutations linked to breast and ovarian cancer, depends on biological identity? Chemically modifying an isolated gene does not alter its biological heart (nucleotide sequence). Accurately detecting BRCA mutations would be impossible without this biological identity.

Although promoting innovation is a laudable goal, the Federal Circuit’s broadening of what constitutes patent-eligible subject matter missed the bigger Constitutional target.

The Intellectual Property clause of the Constitution empowers Congress to grant exclusive rights, such as patents and copyrights, for “limited timed times to promote Progress of Science and the Useful Arts.”

The Constitutional mandate to promote progress includes more than stimulating innovation and must include balancing any grant of exclusive rights against providing access to basic knowledge. Patenting products of nature such as isolated genes and gene sequences prevents access to these basic research tools during the term of the patent. This impedes rather than promotes progress and is therefore in direct violation of the IP clause.

It is the role of Federal Courts, as the keeper of the Constitution, to ensure that any analysis of the plain language of Section 101 of the Patent Act and controlling case law is in harmony with the Constitutional mandate to promote progress of the useful arts.

The Federal Circuit should have taken this role seriously and upheld the lower court’s invalidation of the BRCA isolated genes and gene sequence patents as patent-ineligible subject matter. Viewing these genes as chemically different despite their biological equivalence is cheating the system.

If the BRCA gene patents were invalidated, Congress could then step in and legislate a new “Constitutional” framework of exclusive rights for this subject matter. Congress would likely gather industry, academic and public stakeholders together to craft a hybrid statute that would promote innovation as well as provide much-needed access to these basic upstream research tools.

Given the strong desires of the plaintiffs in the Molecular Pathology case to gain greater access to the isolated BRCA genes for the public, an appeal for an en banc hearing by the Federal Circuit or an appeal directly to the Supreme Court is likely.

I remain hopeful that the reviewing Court will be mindful of its role as the keeper of the Constitution and interpret the Patent Act’s subject matter limitation to exclude the BRCA genes as patent-ineligible products of nature. Only then, can we begin the appropriate legislative dialogue on drafting a “progress-promoting” isolated bioproducts statute which properly balances access against innovation.

This is going to be a long conversation and the courts must ensure that the public gains uniform access to these much-needed basic research tools.

Wake Forest University Law Professor Simone Rose’s research specializes in the intersection of patent law with biotechnology and stem cell research.

CytRx’s INNO-206 in Combination Therapy Induces Complete Remissions in Aggressively Growing Ovarian Cancer Tumor Model

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Posted 01 Aug 2011 — by James Street
Category doxorubicin conjugate INNO-206, Ovarian, Sarcoma

press release

Aug. 1, 2011, 8:30 a.m. EDT

INNO-206 Combination Therapy Could Reduce Toxicity and Improve Tumor Response

 

LOS ANGELES, Aug 01, 2011 (BUSINESS WIRE) — –Study Results Published in Peer-Reviewed Journal Investigational New Drugs

CytRx Corporation CYTR -4.10% , a biopharmaceutical company specializing in oncology, today announced the achievement of complete remissions in aggressively growing in vivo ovarian cancer tumors treated with a combination of low doses of CytRx’s tumor-targeted albumin-binding doxorubicin conjugate INNO-206 and the commonly prescribed cancer treatment doxorubicin.

The study evaluated the antitumor efficacy of INNO-206 in an ovarian xenograft cancer model in animals, alone and in comparison to doxorubicin, each at their respective maximum tolerated doses (MTDs) and in combination at half of their respective MTDs. Doxorubicin at its optimal dose showed only a moderate effect in the animal model. In contrast, INNO-206 at its optimal dose induced complete remissions, and the increased effectiveness was statistically significant compared to the doxorubicin-treated group. Administering either drug by itself resulted in significant body weight loss; however, weight loss was significantly reduced when the drugs were given in combination at the lower doses. The results were published on-line ahead of print in the original article, “Combination therapy with albumin-binding prodrug of doxorubicin (INNO-206) and doxorubicin achieves complete remissions and improved tolerability in an ovarian A2780 xenograft model,” in the peer-reviewed journal Investigational New Drugs ( http://www.springerlink.com/content/v4286257326571wm/ ).

Steven Kriegsman, CytRx’s President and CEO, said, “This trial exemplifies the importance of our on-going relationship with the inventor of INNO-206, Dr. Felix Kratz, Head of the Division of Macromolecular Prodrugs at the Tumor Biology Center in Freiburg, Germany. We are excited about the progress with INNO-206 and are looking forward to reporting our Phase 1b clinical trial results in soft tissue sarcomas in the coming months.”

“The achievement of complete remissions in this aggressively growing tumor model is notable,” said Felix Kratz, Ph.D. “We were indeed surprised that our experimental design demonstrated that the combination of INNO-206 and doxorubicin at lower doses achieved complete tumor remissions combined with the best tolerability. Previous experience in other animal model tumors have shown no or only moderate tumor inhibition with lower doses of INNO-206 or doxorubicin administered as single agents.

“The most likely explanation for the combination therapy’s superior results is due to the different and complementary tumor distribution patterns of the two doxorubicin formulations. Indeed, very recently we have obtained complete remissions with an optimized combination schedule of INNO-206 and doxorubicin without any signs of body weight loss in a pancreatic xenograft model which essentially does not respond to conventional chemotherapy at all. These results open a new avenue of combining both drugs at higher doses against resistant or refractory tumors,” he added. “We will report on our new results in the next few months.”

Daniel Levitt, M.D., Ph.D., Chief Medical Officer at CytRx said, “Due to the heterogeneous nature of cancer tumors, we expect that cancer treatment in the future will increasingly become more personalized and include combinations of therapies, rather than a monotherapeutic approach. The fact that INNO-206 in a combination therapy was able to achieve complete remissions while lowering the dose level of both agents has the potential to reduce toxicity and improve tolerability.”

CytRx holds the exclusive worldwide rights to INNO-206, a tumor-targeted doxorubicin conjugate. INNO-206 was designed to reduce adverse events by controlling drug release and preferentially targeting solid tumors. The Company recently announced the safe delivery of INNO-206 at doses more than 4-times higher than the standard doxorubicin dose in its open-label Phase 1b safety and dose escalation clinical trial in soft tissue sarcomas with INNO-206. CytRx plans to initiate a Phase 2b clinical trial as a treatment for soft tissue sarcomas in 2011, following the Phase 1b dose escalation safety trial. Previous studies have shown INNO-206 efficacy in tumor models of breast, ovarian, small cell lung cancer, renal cell cancer and pancreatic cancers. Several other chemotherapy agents have been attached to the linker used for INNO-206, including paclitaxel, camptothecin, cisplatin and methotrexate, and may be incorporated into future clinical development by the Company.

About CytRx Corporation

CytRx Corporation is a biopharmaceutical research and development oncology company engaged in the development of high-value human therapeutics. The CytRx oncology pipeline includes three programs in clinical development for cancer indications: INNO-206, tamibarotene and bafetinib. With its tumor-targeted doxorubicin conjugate INNO-206, CytRx plans to initiate a Phase 2b clinical trial as a treatment for soft tissue sarcomas in 2011, following the Phase 1b dose escalation safety trial. The Company is evaluating bafetinib in the ENABLE Phase 2 clinical trial in high-risk B-cell chronic lymphocytic leukemia (B-CLL) and the PROACT Phase 2 clinical trial in advanced prostate cancer, and is conducting a pharmacokinetic clinical trial in brain cancer. CytRx’s pipeline also includes tamibarotene, which it is testing in a double-blind placebo-controlled Phase 2 clinical trial in patients with non-small-cell lung cancer, and which is in a registration clinical trial as a treatment for acute promyelocytic leukemia (APL). For more information on the Company, visit http://www.cytrx.com .

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Such statements involve risks and uncertainties that could cause actual events or results to differ materially from the events or results described in the forward-looking statements, including the risk that any future human testing of INNO-206 in combination with doxorubicin as a therapy for cancer, including ovarian cancer, might not produce results similar to those seen in preclinical studies, risks and uncertainties related to the outcome, timing and results of CytRx’s Phase 1b clinical trial for INNO-206 in patients with advanced solid tumors or planned Phase 2b clinical trial for INNO-206 as a treatment for soft tissue sarcomas, the risk that INNO-206 might not show greater efficacy than doxorubicin notwithstanding the administration of higher doses than the standard of care, the risk that additional longer-term dosing of INNO-206 might cause adverse events not seen to date in CytRx’s Phase 1b trial, uncertainties regarding whether INNO-206 effectively targets doxorubicin to tumors, uncertainties regarding regulatory approvals for current and future clinical testing of INNO-206 and the scope of the clinical testing that may eventually be required by regulatory authorities for INNO-206, the significant time and expense that will be incurred in developing any of the potential commercial applications for INNO-206, including for soft tissue sarcomas, the risk that any future human testing of INNO-206 for soft tissue sarcomas might not produce results similar to those seen in animals, risks related to CytRx’s ability to manufacture its drug candidates, including INNO-206, in a timely fashion, cost-effectively or in commercial quantities in compliance with stringent regulatory requirements, risks related to CytRx’s need for additional capital or strategic partnerships to fund its ongoing working capital needs and development efforts, including any future clinical development of INNO-206, and the risks and uncertainties described in the most recent annual and quarterly reports filed by CytRx with the Securities and Exchange Commission and current reports filed since the date of CytRx’s most recent annual report. All forward-looking statements are based upon information available to CytRx on the date the statements are first published. CytRx undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE: CytRx Corporation

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