Our laboratory research focuses on the role of CYP3A enzymes in the growth of prostate and breast cancer. Current work in the lab is focused on understanding the role of CYP3A5 as modulator of androgen receptor signaling and its influence on the therapeutic efficacy of androgen deprivation therapy in prostate cancer. As endocrine therapy resistant breast cancer gains sensitivity to antiandrogens we are also looking into the role of CYP3A4 in gaining therapy resistance in estrogen receptor positive breast cancer. Our lab also focuses on understanding the role of fatty acid signaling in circulating tumor cells (CTCs) which are important indicators of metastasis and associated with poor prognosis.
CYP3A5 in Prostate Cancer
Studies in our laboratory have indicated that CYP3A5 modulates AR signaling by modifying nuclear translocation of AR in prostate cancer. As androgen-targeted therapy plays a central role in the treatment of advanced metastatic prostate cancer our lab is involved in understanding molecular mechanism by which CYP3A5 modulates AR signaling towards developing a new target to block AR nuclear translocation. Since CYP3A5 is also involved in metabolizing several drugs many of which are commonly prescribed to prostate cancer patients we are also testing the effect of polypharmacy on androgen deprivation therapy.
CYP3A4 in Breast Cancer
Many resistant breast cancers switch to androgen receptor (AR) signaling and there is accumulating evidence anti-androgen therapy therefore be used to treat these cancers. Since CYP3A5 is known to regulate AR signaling our lab is currently studying the role of CYP3A in regulating AR expression in resistant and native ER+ breast cancer cells. Since CYP3A4 is a major hepatic microsomal enzyme expressed in breast cancer and metabolizes 50% of prescription drugs, our lab if focused on understanding if treatment efficacy may be altered in women taking CYP3A inducer/ inhibitors and undergoing endocrine therapy.
Fatty acid signaling in cancer cells and circulating tumor cells:
We recently published that cancer cells circulating tumor cells uptake fatty acids rapidly and store then as lipid droplets. Our lab is currently focused on studying the altered lipid signaling in cancer cell and circulating tumor cells. Intracellular lipid could serve as a biomarker for CTCs which could be sensitively detected with CARS microscopy in a label-free manner. Strong affinity for lipid by metastatic prostate cancer cells could be used to improve detection sensitivity and therapeutic targeting of prostate CTC.