(PARP Inhibitors Video) At 2010 ONS conference in San Diego (ONS stands for “Oncology Nursing Society”), one of the hot subjects when it comes to the treatment of ovarian cancer was PARP Inhibitors. In this video, Paula J. Anastasia, RN, MN, talks about ovarian cancer recurrence and at 2:55 into the video she begins to talk about PARP inhibitors, giving an explanation of what it is and how it is given to patients in clinical trials…
(PARP Inhibitors News) Merrill J. Egorin, MD an acclaimed PARP Inhibitors and cancer researcher died on August 7, 2010 at the age of 62. Dr. Egorin’s death came five years after being diagnosed with multiple myeloma, which is a cancer of the plasma cells in bone marrow. Dr. Egorin had been a professor of medicine and pharmacology at the University of Pittsburgh Cancer Institute. Last year he won a prestigious $500,000 award from the American Society of Clinical Oncology (ASCO) for his outstanding cancer research. The award money is to be used to further the training of translational research-focused oncologists.
Dr. Egorin was passionate about the effectiveness of PARP inhibitors, predicting a year ago that the publicity and popularity of PARP inhibitors would explode. PARP inhibitors have shown promise in killing cancer cells in certain breast cancer and ovarian cancer patients undergoing chemotherapy. PARP inhibitors help stop cancer cell DNA from repairing itself after chemotherapy. Studies have shown great promise. Dr. Egorin has been pushing for the expansion of the research of PARP inhibitors because of the promise they showed and because of its gain in popularity. Many news organizations, in June 2009, dubbed PARP inhibitors as “the wonder cancer drug” even though a lot of research and studies are still needed before PARP inhibitors can be used on a mass scale. Current research is mainly targeting breast and ovarian cancer, but it’s widely believed that PARP inhibitors will be effective in the treatment support of other cancers.
ASCO describes its $500,000 Translation Research Professorship Award as:
The Translational Research Professorship is awarded to physicians who are full-time professors at academic medical centers and have made significant contributions to the field of cancer research. This year’s recipient will receive $500,000 over five years to support continued efforts to bring advances in basic sciences into the clinical arena, and will also serve as a mentor for other translational researchers.
Since Dr. Egorin died one year after receiving the five-year award, it is unknown at this time how the rest of the award/program will be handled. However, ASCO did put out the following statement after learning of the death:
The ASCO Cancer Foundation® is deeply saddened by the passing of one of our Translational Research Professors, Dr. Merrill Egorin. Dr. Egorin was a world-class scientist, a wonderful colleague, and a truly inspired and dedicated teacher and mentor. He will be missed by the entire oncology community. Many of our staff had the honor to work with him while he taught our Grants Writing Workshops, actively performed TACF-funded research, was interviewed for our video series, and mentored many young investigators on their first grants. We saw first-hand what an inspiration he was and our hearts go out to his family and colleagues in this difficult time. We are confident that his legacy of passionate teaching and mentorship will live on through the many physician-scientists that he trained and we are glad that we were able to support him in these endeavors.
Dr. Egorin will be greatly missed with the PARP Inhibitors community, especially with his push to expand the research within this field.
Editor’s Note: The following is a press release based on a recent PARP Inhibitor study/trial. We have not edited this press release in any way. The source of the press release is Penn Medicine. It is our editorial policy to always let you know when something we publish is a press release and who the source of the press release is.
A novel therapy designed to attack tumors in patients with a genetic mutation in either BRCA1 or BRCA2, slowed tumor growth in 85 percent of advanced breast cancer patients treated in a small study, researchers report in the July 6 issue of The Lancet.
“That is really an enormous response rate in a population of patients who have received a median of three prior therapies,” says study co-author Susan M. Domchek, MD, associate professor of Medicine, University of Pennsylvania School of Medicine, and director of the Cancer Risk Evaluation Program at Penn’s Abramson Cancer Center.
“This is the first time that we have been able to take the genetic reason a person has developed cancer and make it a target,” Domchek says. “Most of the time we look at what is going on in the tumor itself and then figure out how to target it. But in this situation, the women all had an inherited mutation in either the BRCA1 or BRCA2 gene and we could exploit that weakness in the tumor. It is a strategy that may cause fewer side effects for patients.”
The new agent, called olaparib, inhibits a protein called poly(ADP-ribose) polymerase (PARP). Both PARP and the BRCA proteins are involved in DNA repair. And while cells seem to be able to do without one or the other, inhibiting PARP in a tumor that lacks a BRCA gene is too much for the cells, and causes them to die.
“If you put too much stress on the cancer cell, it can’t take it and it falls apart,” Domchek says. Because the non-tumor cells in a patient with an inherited BRCA mutation still retain one normal copy of the BRCA gene, they are relatively unaffected by PARP inhibition. “These drugs may be very potent in tumor cells and much less toxic in normal cells. That is important from the perspective of cancer treatment,” Domchek says.
The international study enrolled 54 patients in two groups. The first group of 27 women received 400 mg oral olaparib twice daily and the second group of 27 patients received 100 mg oral olaparib twice daily. The higher dose appeared to have more activity against the disease, with one patient (4%) having a complete resolution of her tumor and ten (37%) showing substantial tumor shrinkage. Another 12 (44%) women had stable disease or some tumor shrinkage, but not enough to be considered a partial response by standard criteria. In the low dose group, six (22%) patients showed substantial shrinkage and 12 (44%) had some tumor shrinkage or stable disease.
Although the results look good thus far, Domchek says more clinical trials will be necessary before olaparib or other PARP inhibitors in development will be ready for use in regular practice. “It is important for patients to join those clinical trials because we need to determine how best to use these drugs, on their own or in combination with other agents,” she said. “And we need to establish definitively that they are better than other drugs.”
The PARP inhibitors are a transition in the field of cancer drug development. “This is a different way of looking at cancer therapeutics,” Domchek says. “In oncology, this is really one of the first times that we’ve seen drugs being developed on the basis of inherited susceptibility – and that may open up a whole new avenue of drug development.”
Penn was one of just six centers in the United States to participate in the clinical trial. The trial was led by Andrew Tutt, MD, of the Breakthrough Breast Cancer Research Unit at Kings College London School of Medicine. Breakthrough Breast Cancer is a pioneering charity dedicated to the prevention, treatment and ultimate eradication of breast cancer through research, campaigning and education. Co-authors on the study are Mark Robson (Memorial Sloan-Kettering Cancer Center, New York), Judy E Garber (Dana-Farber Cancer Institute, Boston), M William Audeh (Samuel Oschin Cancer Institute, Los Angeles), Jeffrey N Weitzel (City of Hope Comprehensive Cancer Center, Duarte, CA), Michael Friedlander (Prince of Wales Cancer Centre, Sydney, Australia), Banu Arun (MD Anderson Cancer Center, Houston), Niklas Loman (Skane University Hospital and Lund University Hospital, Sweden), Rita K Schmutzler (University Hospital Cologne, Germany), Andrew Wardley (The Christie Hospital NHS Foundation Trust, Manchester, UK), Gillian Mitchell (Peter MacCallum Cancer Centre, East Melbourne, Australia), Helena Earl (University of Cambridge and NIHR Cambridge Biomedical Research Centre, UK), and Mark Wickens and James Carmichael (AstraZeneca, Macclesfield, UK).
AstraZeneca provided funding for the trial. Dr. Domchek has no ties to AstraZeneca and no other disclosures to report.
(PARP Inhibitors News) Here is a news story by TV station WAVY that talks about the promise shown by PARP Inhibitors in the treatment of breast cancer. The news story follows the progress of one triple negative breast cancer patient, Sharon Price, who was able to get into a study for this new type of cancer drug treatment. Here is the WAVY story, “PARP Inhibitors Show Promise”…
(PARP Inhibitors Videos) This is a presentation that was given at the 2009 ASCO (American Society of Clinical Oncology) event. The lecture is about how chemotherapy combined with PARP Inhibitor BS-201 may be an effective new treatment option for triple negative breast cancer. The person speaking is Joyce OShaughnessy, MD from the Baylor-Charles A. Sammons Cancer Center in Dallas, Texas. Here’s what she has to say about PARP Inhibitors and Triple Negative Breast Cancer…
(Breast Cancer and Parp Inhibitors) Below are two videos (part 1 and part 2) of a lecture given by Dr. Michael Danso of the Virginia Oncology Associates. He was asked to talk at a program called “The Many Faces of Cancer”. For his talk, he tackled new breast cancer treatments, talking about several new drugs, including Parp Inhibitors. If you’re only interested in hearing what he says about Parp Inhbiitors, then start with the second video and fast forward (or click) to 5:16.
Part 1:
Part 2 (Parp Inhibitor talk starts at 5:16):
Below is a great lecture video by Dr. Devon Webster on the subject of Parp Inhibitors, what they are, and how they work. She not only does a great job of explaining it in layman’s terms, but also has a sense of humor. From the video,
“In cancer our goal is to kill the cells that are rapidly dividing. And if we damage the DNA with an agent like chemotherapy and there’s something like PARP that can come along and fix it, that’s not so good because we want it to stay damaged and we want it to then die.”
PARP inhibitors help prevent the ability for cells to repair itself. They inhibit PARP.
Here is Dr. Devon Webster:
(Ovarian Cancer Parp Inhibitors Research) The experimental cancer drug olaparib, a drug in the promising class of drugs known as PARP Inhibitors, produced promising results in patients with ovarian cancer linked to an inherited BRCA1 or BRCA2 gene mutation. The trial results were published in the Journal of Clinical Oncology on April 19th, 2010.
Scientists at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital, working with pharmaceutical company KuDOS Pharmaceuticals, a subsidiary of AstraZeneca, found that olaparib shrank or stabilized tumors in approximately half of ovarian cancer patients possessing BRCA1 or BRCA2 mutations.
The five-year survival rate for ovarian cancer is just 40 per cent as the majority of patients are diagnosed with an advanced form of the disease. Most patients initially respond well to radical surgery and platinum and taxane-based chemotherapy, but relapse after an average of 18 months. Subsequent treatments generally become less effective as patients build up resistance.
“There is an urgent need to find new drugs for women diagnosed with ovarian cancer,” says Professor Stan Kaye, Head of the Section of Medicine at the ICR. “Olaparib is still in early-stage testing but the results so far are very encouraging. These findings raise the possibility that carefully selected patients in future may well be offered olaparib as an alternative to chemotherapy during the course of their treatment.”
Between 2005 and 2008, about 50 women with confirmed or suspected BRCA1 or BRCA2 mutations began treatment with olaparib in a dose escalation and single-stage expansion of a Phase I trial. Twenty patients responded with their tumors shrinking or with significant falls in their ovarian cancer marker CA125, or both. The disease also stabilized in three patients. The drug was effective for an average of seven months. Notably, several patients are still taking olaparib (for nearly two years). Drug side-effects were generally mild, especially when compared to current chemotherapy treatments.
Platinum-based chemotherapy, particularly carboplatin, is one of the main treatments used for ovarian cancer. When this treatment ceases to be effective, theoretically, olaparib might be less effective too, so the ICR scientists examined whether olaparib would still benefit patients whose response to previous platinum-based drugs was limited. Finding new drugs to treat these “platinum-resistant” ovarian cancer patients (those who relapsed within six months of previous platinum therapy) is a particularly high priority as they have a lower chance of benefiting from re-treatment with chemotherapy and a poorer prognosis.
The research team found that the clinical benefit rate with olaparib was indeed higher — 70% — among patients with “platinum-sensitive disease” (disease recurrence more than six months after previous platinum therapy). Crucially, however, the clinical benefit rate was still 46% in platinum resistant patients.
Other Study Results:
> 50 patients participated in the study (13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval).
> 20 patients (40%) achieved complete or partial responses under RECIST (Response Evaluation Criteria in Solid Tumors) criteria and/or tumor marker (CA125) responses.
> 3 patients (6.0%) maintained RECIST disease stabilization for more than 4 months.
> Overall clinical benefit rate (complete response + partial response + stable disease) = 46%.
> Median response duration was 28 weeks.
> There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory patient subgroups (69%, 45%, and 23%, respectively).
> Analyses indicated associations between platinum sensitivity and extent of olaparib response
Dear Parp Inhibitors Cancer,
What is Olaparib?
Olaparib is an inhibitor of the enzyme Poly ADP ribose polymerase (PARP). It was one of the first PARP inhibitors developed by KuDOS Pharmaceuticals that was later bought out by AstraZeneca. More specifically olaparib is an experimental drug that has been shown in studies to shrink or stabilize tumors in almost 50% of ovarian cancer patients possessing BRCA1 or BRCA2 mutations. Studies so far haven’t shown major side effects in people, but those who did have them reported some fatigue, somnolence, nausea, loss of appetite and thrombocytopenia.
In the most simplistic form of explanation, an olaparib operates by turning a tumor’s specific genetic defect against itself. In vulnerable cells, olaparib blocks the repair of naturally occurring breaks in the DNA, which healthy cells are normally able to repair. Thus the vulnerable cancer cells (considered those with an existing defect in a DNA repair pathway caused by a mutation in the BRCA1 or BRCA2 genes) are unable to repair themselves. Those cells then die.
In a recent feature story on the use of Parp Inhibitors for the treatment of breast and ovarian cancer in women, Dr. Charles L. Vogel does a good job of explaining, in layman terms, what a Parp Inhibitor is and how parp inhibitors treat cancer. From the video:
What happens is when different chemotherapy drugs act on the DNA of a tumor cell, they cause damage. But the tumor cells are smart and they can repair that damage. Yet the PARP inhibitor is able to inhibit the ability of the tumor to repair that damage… if you can inhibit DNA repair then the tumor will be destroyed.
Here’s the full video…
| © 2010 PARP Inhibitors Cancer |
