Researchers find possible key to preventing chemotherapy resistance in ovarian cancer

September 15, 2011 in Cancer

For patients with ovarian cancer and their physicians, resistance to chemotherapy is a serious concern. However, researchers at Moffitt Cancer Center have identified a molecular pathway that may play a key role in the evolution of chemotherapy resistance. They are hopeful that the discovery may lead to therapies that are tailored to individual patients with ovarian cancer; reversing resistance to chemotherapy and improving survival from the disease.

"Few clinical or biologic events affect survival for patients with more than the way their tumors respond to chemotherapy," said Johnathan Lancaster, M.D., Ph.D., senior author on a study into chemotherapy resistance recently published in the journal (17:00, 2011). "We identified a pathway called the 'BCL2 antagonist of cell death,' or BAD, and determined that the activity of the BAD pathway may have more influence on survival than the volume of after primary surgery."

According to Lancaster and colleagues, the discovery of BAD opens the door to using the pathway as a biomarker to identify patients with the highest-risk ovarian cancer, which are genetically programmed to be resistant to chemotherapy; enabling physicians to identify patients who might benefit from drugs that inhibit the BAD pathway such that chemo-resistance is reversed.

"Targeted therapies that increase a tumor's sensitivity to chemotherapy offer the potential to improve patient survival," explained Lancaster, chair of the Department of Women's Oncology and director of the Center for Women's Oncology at Moffitt.

By treating in a test tube (in vitro) with a chemotherapy drug and observing which became most active, the researchers identified the BAD pathway. To further analyze the activity of the BAD pathway and levels of the BAD protein, the researchers examined tumor specimens and genomic information from almost 300 patients with advanced ovarian cancer. A 47-gene BAD pathway signature was developed and was found to be associated with survival. Subsequent in vitro tests on ovarian cancer cells suggest that it may be possible to inhibit the BAD pathway and reverse resistance to chemotherapy.

"Intriguingly, patients who had lots of cancer remaining at the conclusion of their surgery but whose tumors had low levels of pBAD protein, had better survival than patients with very little cancer remaining following surgery, but who had high levels of pBAD protein," said Lancaster. "Although our data highlights the importance of this newly identified pathway, not all cell line samples showed associations between chemotherapy resistance and BAD pathway genes. There are likely many other pathways and processes contributing to chemotherapy resistance."

The researchers concluded that although more research is necessary, BAD pathway-based biomarkers could open the door to personalized treatment for ovarian cancer by placing women in high-risk and low-risk groups based on their genetic profile for the BAD pathway and protein. Treatments could be selected for each patient according to the status of their BAD pathway.

Provided by H. Lee Moffitt Cancer Center & Research Institute

not rated yet  

Rank not rated yet
Relevant PhysicsForums posts
  • A question about drug tolerance
    createdMay 23, 2012
  • Poor nutrition leading to overeating?
    createdMay 23, 2012
  • Math and dyslexia?
    createdMay 21, 2012
  • portable metabolism meter?
    createdMay 21, 2012
  • Rare medical conditions on 20/20 tonight
    createdMay 18, 2012
  • "Good" Cholesterol in Doubt
    createdMay 17, 2012
  • More from Physics Forums - Medical Sciences

More news stories

Skp2 activates cancer-promoting, glucose-processing Akt

HER2 and its epidermal growth factor receptor cousins mobilize a specialized protein to activate a major player in cancer development and sugar metabolism, scientists report in the May 25 issue of Cell.

Cancer created 13 hours ago | popularity not rated yet | comments 0 | with audio podcast

Pancreatectomy OK without downstaging from therapy

(HealthDay) -- Pancreatectomy improves median survival in pancreatic cancer patients even when presurgical neoadjuvant therapy does not lead to radiographic downstaging of tumors, according to a study published ...

Cancer created 14 hours ago | popularity not rated yet | comments 0

Common therapies for basal cell carcinoma offer similar survival

(HealthDay) -- For patients with superficial basal cell carcinoma (sBCC), treatment with imiquimod or photodynamic therapy (PDT) results in similar long-term tumor-free survival, according to a review published ...

Cancer created 15 hours ago | popularity not rated yet | comments 0

Cancer may require simpler genetic mutations than previously thought

Chromosomal deletions in DNA often involve just one of two gene copies inherited from either parent. But scientists haven't known how a deletion in one gene from one parent, called a "hemizygous" deletion, can contribute ...

Cancer created 17 hours ago | popularity not rated yet | comments 0 | with audio podcast

New prostate cancer screening guidelines face a tough sell, study suggests

(Medical Xpress) -- Recent recommendations from the U.S. Preventive Services Task Force (USPSTF) advising elimination of routine prostate-specific antigen (PSA) screening for prostate cancer in healthy men are likely to encounter ...

Cancer created 20 hours ago | popularity not rated yet | comments 1


Of mice and mental models: Neuroscientific implications of risk-optimized behavior in the mouse

(Medical Xpress) -- Regardless of an organism’s biological complexity, every encephalized animal continuously makes under-informed behavioral choices that can have serious consequences. Despite its ubiquity, ...

Tongue analysis software uses ancient Chinese medicine to warn of disease

For 5,000 years, the Chinese have used a system of medicine based on the flow and balance of positive and negative energies in the body. In this system, the appearance of the tongue is one of the measures used to classify ...

Inherited DNA change explains overactive leukemia gene

A small inherited change in DNA is largely responsible for overactivating a gene linked to poor treatment response in people with acute leukemia.

Early physical therapist treatment associated with reduced risk of healthcare utilization and reduced overall healthcare

A new study published in Spine shows that early treatment by a physical therapist for low back pain (LBP), as compared to delayed treatment, was associated with reduced risk of subsequent healthcare utilization and lower ...

New device allows pacemaker patients to safely undergo MRIs

For many, it's a medical conundrum: The very pacemaker keeping their heart in rhythm prevents them from undergoing an MRI to diagnose other ailments, because interaction between the two devices could prove deadly.

First study to suggest that the immune system may protect against Alzheimer's changes in humans

Recent work in mice suggested that the immune system is involved in removing beta-amyloid, the main Alzheimer's-causing substance in the brain. Researchers have now shown for the first time that this may apply in humans.