Research into improving the effectiveness of therapies for breast cancer continues at a rapid pace in the Breast Cancer Program. More than 40 clinical trials for breast cancer are taking place at Dana-Farber or our affiliated institutions. Researchers are working to develop new agents for drug-resistant cancers, identify additional subtypes of tumors that respond to targeted treatments, uncover the biochemical signs of a tumor’s aggressiveness and vulnerability to therapy, and devise new approaches to cancer prevention and supportive care.
Susan F. Smith Center for Women’s Cancers (SSC) investigators are tackling cancer on multiple fronts, including triple-negative breast cancers (so called because they lack estrogen, progesterone, and human epidermal growth factor receptors that are known to fuel most breast cancers), HER2-positive breast tumors that have become resistant to trastuzumab (Herceptin), and metastatic breast cancers.
Promising laboratory research by Dana-Farber scientists has implicated a microRNA molecule called miR-182 as a source of decreased expression of a protein made from the BRCA1 gene in women who develop breast cancer without inheriting a susceptibility to the disease. (MicroRNAs are tiny jots of RNA whose role in gene expression has recently begun to be unraveled by scientists.)
This finding builds on earlier research into the link between reduced BRCA1 expression and breast cancer. Several Dana-Farber researchers are conducting clinical trials of new drugs called PARP inhibitors in women whose breast cancer arose from an inherited mutation in BRCA1 (as well as in patients with triple-negative breast cancers). The theory is that cells with poorly or non-functioning BRCA1 repair proteins will become dependent on another DNA repair pathway involving an enzyme called poly (ADP-ribose) polymerase – or PARP. The combined loss of BRCA1 and PARP (via inhibitors) leaves cancer cells too damaged to survive.
In clinical trials, PARP inhibitors have shown promise in breast cancer patients with inherited BRCA1 mutations, leading researchers to open new trials of the drugs to patients without an inherited susceptibility to the disease.
SSC investigators are also continuing research into the safety and effectiveness of shutting down or blocking a protein called PI3 kinase which early research has shown can lead to cancer cell death.
Investigators have widened their focus from a concern with cancer cells themselves to a consideration of the interactions of tumor cells with surrounding, healthy tissue. SSC researchers have shown that the ability of tumor cells to disrupt the normal development of milk duct cells enables the tumor cells to escape the ducts and travel to other parts of the body; that is, to metastasize. Specifically, there are several studies of drugs that may act against breast tumor cells that have spread to the brain, a particularly challenging site.
Courtesy of Dana-Farber Cancer Institute
Turning Points 2011