UCLA Jonsson Comprehensive Cancer Center
UCLA Jonsson Comprehensive Cancer Center is the beneficiary of a $850,000 grant from Noreen Fraser Foundation, disbursed over three years (beginning in 2010) in support of the work of Drs. John Glaspy and Dennis Slamon. John A. Glaspy, M.D., M. P.H, is a researcher and oncologist who has gained a national reputation in clinical medicine as an acute diagnostician and outstanding clinician.
His research areas include: studies to test the ability to successfully treat breast cancer with stem cell transplantation; understanding the role of gene therapy in cancer; showing that a specific, low-fat diet can alter the composition of human breast tissue in a way that could make it resistant to breast cancer.
Dennis J. Slamon, M.D., Ph.D., is a highly respected physician/scientist whose work resulted in the first molecularly targeted treatment for breast cancer, a drug that attacks the disease by targeting defective genes. For 12 years, Slamon and his colleagues conducted the laboratory and clinical research that led to the development of Herceptin, which targets a specific genetic alteration found in about 25 percent of breast cancer patients.
***** UPDATE *****
NFF Funded Breast Cancer Research at UCLA’s Jonsson Comprehensive Cancer Center Leads to Phase III Trial
Background
We now appreciate that breast cancer is not one disease but many distinct diseases and that the only thing that all breast cancers share in common is the organ in which they arise. Consequently, breast cancer is now classified, based on gene expression patterns, into several different subtypes. These include the hormone receptor positive (ER+) groups, HER2-positive, basal-like, and normal-like, although there can be some overlap in characteristics among the subtypes. Importantly, each of these subtypes have distinct clinical outcomes and prognosis.
Approximately two thirds of breast cancers are estrogen receptor positive (ER+). Modification of estrogen activity or synthesis represents the treatment of choice for these types of cancers. There are several estrogen directed therapies available including Tamoxifen, aromatase inhibitors and direct estrogen receptor down -regulators such as Fulvestrant (Faslodex).
The UCLA Translational Oncology Program has been focusing on other molecular targeted agents in the treatment of ER+ breast cancer that will provide an alternative to chemotherapy when ER+ breast cancers are inherently resistant to or develop a resistance to anti-estrogen agents.
Targeting the Cyclin D:cdk-4/6 Pathway. Cell growth and division in normal breast cells is tightly regulated. One of the main proteins involved in theregulation is the cyclin D kinases 4 and 6. These proteins interact with other proteins (Cyclin D and RB) to tell a cell when to grow and when not to grow. In cancer cells, this pathway is often dysregulated allowing for uncontrolled tumor growth. UCLA researchers have evaluated investigational drugs that block cdk-4/6 function with the goal that by inhibiting this function in cancer cells, they can restrict their growth.
As part of the laboratory research efforts funded by the Noreen Fraser Foundation, UCLA scientists screened its panel of human breast cancer cell lines and found that ER+ breast cancer cells seem to be particularly dependent on cdk-4/6 function. Their research found that blocking it with a novel agent, a drug currently named “PD 0332991″, which is a selective inhibitor of cdk-4/6, researchers saw that ER+ breast cancer cell lines stopped growing. In addition, when taken in combination with estrogen receptor targeted drugs like Tamoxifen, the result was even greater.
The results were brought to the clinic in Phase I and Phase II clinical trials for women with advanced ER+ breast cancer. The early results from these clinical studies was astounding. The women who received the combination of the new drug (“PD 032991”) and an estrogen receptor targeting agent had a 64% improvement in the time to their disease progression and no significant side effects. The impact was greater than any other therapeutic drug tested in this group of women to date. Because of the tremendous success of the research, a Phase III, randomized, multi-national, registrational trial is now being planned, with Pfizer dedicating $190 million to further the study. We are extremely excited about these initial results that have been directly translated out of some of the work conducted with our support.
