Improving the efficacy of retinoic-acid-based therapies in triple-negative breast cancer

Some patients with breast cancer are diagnosed with triple-negative breast cancer (TNBC). These patients have tumors that have do not express the estrogen and progesterone hormone receptors (ER and PR), or the Her2 protein. Many existing treatments for breast cancer target ER, PR, or Her2; thus, the survival rate of TNBC patients is significantly lower as they cannot be effectively targeted with these therapies. It is important to develop new treatments for TNBC tumors to minimize the burden of this disease on patients, their families, and the Canadian health care system. Treating these patients is even more complex than initially believed, as not all TNBC tumors are alike. Recent research has identified that TNBCs can be further separated into different subtypes based on the genes expressed within the tumor, as well as their sensitivity to different anti-cancer agents. My research is focusing on these differences between TNBC subtypes to determine which patients will benefit from an existing anti-cancer agent, retinoic acid (RA). RA is used in the treatment of some leukemias; however, it has not achieved its potential in the treatment of other cancers, like breast cancer. I hypothesize that the growth of tumors from some subtypes of TNBC can be effectively halted, while RA may promote the growth of other subtypes. These opposing effects may explain the apparent failures of RA against breast cancer in clinical trials. Our recent work has identified different models which illustrate these effects. Confirming that the effects of RA in TNBC are dependent on the subtype will allow doctors to identify TNBC patients who will benefit from this treatment. This research will have important benefits for cancer care in Canada. Identifying TNBC patients who will benefit from RA treatment and those who will not benefit will improve the effectiveness of RA in clinical trials. A direct benefit of this increased effectiveness will be an improvement in breast cancer patient survival