Faulty proteins may prove significant in identifying new treatments for ovarian cancer
01/13/12 Portland, Ore.
OHSU Knight Cancer Institute study results suggest that more patients than initially thought could potentially be treated with a new class of drugs, PARP inhibitors
A constellation of defective proteins suspected in causing a malfunction in the body’s ability to repair its own DNA could be the link scientists need to prove a new class of drugs will be effective in treating a broad range of ovarian cancer patients, an Oregon Health & Science University Knight Cancer Institute study found.
These research results, published this week in PLoS ONE, have prompted additional exploration into whether the patient population included in clinical trials for drugs that target the enzyme poly ADP ribose polymerase (PARP) should be expanded. Several forms of cancer are more dependent on PARP for their growth than regular cells, which means that targeting these enzymes when they go haywire is a potentially effective way to treat ovarian cancer. Currently PARP inhibitors are being tested with patients who have two types of malfunctioning proteins, BRCA1 or BRCA2. But, the OHSU Knight Cancer Institute study of additional proteins, beyond BRCA proteins, suggests that they too are playing a role in driving ovarian cancer.
Tapping into the potential of PARP inhibitors could change the dynamics of ovarian cancer treatment. There has not been a substantial increase in treatment options for ovarian cancer in the past two decades, said Tanja Pejovic, M.D., Ph.D., gynecologic oncologist at the OHSU Knight Cancer Institute. Pejovic, who led the study of these additional defective proteins, added that the results provide evidence that further research into the role of multiple proteins is warranted.
Only about 10 to 15 percent of women with ovarian cancer have BRCA 1 or BRCA 2 mutations. Pejovic’s study of 186 patients with nonhereditary cancer found that 41 percent who had an early recurrence of the disease also had abnormal levels of the other proteins tracked. In contrast, only 19.5 percent of patients who hadn’t yet had a recurrence of the disease in three years had abnormal levels of these proteins.
"If we are able to identify the proteins that differentiate these patients at risk for early recurrence, this would open up a new direction in ovarian cancer treatment," Pejovic said.
The study — which was supported by the Sherie Hildreth Ovarian Cancer (SHOC) Foundation — focused on proteins that are supposed to assist cells in repairing harmful breaks in DNA strands, a process called homologous recombination (HR). The malfunctioning of HR is not well understood in ovarian cancers where there is no family history of the disease. However, there is evidence that these proteins influence a patient’s ability to respond to drugs and their survival rates after treatment.
Ovarian cancer is the second most common gynecologic cancer and the most common cause of death among women with a gynecologic cancer. About 21,000 ovarian cancer cases are diagnosed annually and about 14,000 deaths occur each year from the disease.
The OHSU Knight Cancer Institute, which helped pioneer the field of personalized cancer medicine, is committed to research that identifies the specific mutations driving each individual patient’s cancer. Other researchers at the Knight Cancer Institute who contributed to the study are: Weiya Z. Wysham, M.D.; Hong Li, M.S., M.D.; Laura Hays, Ph.D.; Jay Wright; Nupur Pande, Ph.D.; and Maureen Hoatlin, Ph.D.
There is wonderful news out of Washington today for women with ovarian cancer and those who care about them. Congress
has passed an omnibus appropriations bill for this fiscal year, which includes everything we asked for!
The Ovarian Cancer National Alliance fought for funding to support critical ovarian cancer research and
education programs. Despite the difficult economy, we won!
- We won $5 million for Johanna’s Law: The Gynecologic Education and Awareness Act,
which received no funding in last year’s appropriations bill.
- We won $4.9 million for the Ovarian Cancer Control Initiative, which was initially
cut from the funding for the Centers for Disease Control and Prevention.
- We won $16 million for the Ovarian Cancer Research Program (OCRP) run by the
Department of Defense. This is a tremendous victory, as the Senate initially proposed funding of just
$10 million.
The Alliance organized a letter,
signed by our Partner Members and colleague organizations, that urged Congress to support the House funding
level of $16 million. The letter noted that “the OCRP’s unique method of funding ovarian
cancer research has yielded tremendous breakthroughs in the fight against ovarian cancer.”
We are grateful to the many members of Congress who supported our requests, especially Representatives Dan Burton
and Rosa DeLauro. They took the lead on
a letter that
encouraged funding for the OCRP, saying “Designed to promote increased flexibility,
OCRP research produces innovative, high impact and valuable results through strategic partnerships between advocates,
lab scientists and clinicians.”
Thank you to all the advocates who sent thousands of emails and made scores
of calls to Congress this year, letting them know just how many Americans are touched by ovarian cancer–and why
we need dedicated funding for education and research. We could not have done this without you.
As of August 2011, there are more than 180 drug shortages reported, including numerous chemotherapeutic agents. Ovarian cancer drugs, including Taxol and Doxil, are in short supply. The Ovarian Cancer National Alliance is working with stakeholders and government authorities to determine the cause of the problem and work towards a solution.
There are shortages in generic drugs and branded drugs. The cause of the shortages is not yet clear, but may include unsafe supplies, production problems or drug company concerns about low prices for generic drugs.
With respect to Doxil, the manufacturer is currently limiting the drug to patients who are already receiving it; no new patients should be started on Doxil. Patients on Doxil should have their physician enroll them in the Doxil CARES Physician Access Program so that the doctor can receive Doxil. The company has not released an estimated date that the shortage will end.
If you are experiencing the effects of a drug shortage, please contact us at:
.
You can read more about this shortage at http://www.ovariancancer.org/drug-shortages/
