Researchers from Baylor College of Medicine have been awarded more than $5 million from Susan G. Komen for the Cure for three new breast cancer research grants, including a prestigious Komen Promise Grant.
Komen Promise Grant
The Komen Promise Grant is a three-year award for a total of $4,066, 940 to study restoration of endocrine therapy sensitivity in recurrent breast cancers. The grant was awarded to principal investigator Dr. Bert O'Malley, chair of molecular and cellular biology at BCM and co-principal investigator Dr. Kent Osborne, director of both the NCI-designated Dan L Duncan Cancer Center and the Lester and Sue Smith Breast Center at BCM.
The Komen Promise Grant will address a very important clinical problem – endocrine therapy resistance.
Most breast cancers are estrogen receptor-positive, meaning that they are fueled by estrogen. Although there are drugs available to target the estrogen receptor, such as tamoxifen or aromatase inhibitors, many tumors eventually become resistant to treatment causing the cancer to return.
"It has been more than a decade since we have introduced new effective endocrine agents into the clinic," said Osborne. "It is clear that new strategies to block this complex system are needed to prevent recurrence."
"We think this resistance could be caused by redundant escape pathways that function as alternate survival signals in the cell that compensate and bypass the tamoxifen therapy block or through steroid receptor coactivator overexpression," said O'Malley. The coactivators function to stimulate the expression of estrogen receptor-dependent genes in breast cancer cells.
"The current endocrine therapies frequently lead to increased expression of these coactivators, which creates these escape pathway genes that promote resumption of tumor growth," said O'Malley.
O'Malley and Osborne hypothesize that this is a major cause of late recurrence of estrogen-receptor positive tumors that initially responded to treatment but become resistant.
With the Komen Promise Grant, they will evaluate novel drug strategies to target this activity and restore sensitivity to endocrine therapy.
After three years, the project will be evaluated for an additional two years of funding.
Investigator Initiated Award
Dr. Yi Li, associate professor in the Smith Breast Center at BCM, and Dr. David Tweardy, professor of medicine – infectious diseases at BCM, received a $900,000, investigator-initiated research award to study an approach to prevent breast cancer through blocking the JAK2-STAT5 pathway – a pathway believed to prevent cell death and promote cell survival, fueling the cancer's growth.
Post-doctoral Fellowship Grant
Additionally, BCM received a $180,000 post-doctoral fellowship grant for Dr. Jin Ah Kim to study the potential role of TLK2 as a therapeutic target in breast cancer.
Kim is a currently a post-doctoral associate in the lab of Dr. Xiaosong Wang, assistant professor in the Smith Breast Center. Dr. Wang and Dr. Rachel Schiff, associate professor in the Smith Breast Center, will co-mentor Kim in this project.
Amplifications (replication of genetic material) of the gene TLK2 are more frequent in advanced breast cancers prone to early and frequent recurrence and metastasis. Kim will study the genetic changes that lead to this and hopefully target the activity.