Dr. Paraskevi Giannakakou’s lab studies the biology of the microtubule cytoskeleton and the molecular mechanisms of action and resistance to drugs that target microtubules (e.g. taxanes) and are used in cancer chemotherapy. Dr. Giannakakou and her team use functional cellular and molecular biology assays coupled with high-resolution microscopy and live-cell imaging to decipher the molecular basis of clinical response and resistance to taxanes and other widely used microtubule inhibitors. The clinical success of microtubule inhibitors, together with their broad spectrum of antitumor activity argues that tubulin represents the single best target identified in clinical oncology.
In prostate cancer, the taxanes are the only chemotherapies used for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). However, most patients progress due to the development of drug resistance.
Currently, the molecular basis of clinical drug resistance remains poorly elucidated. It is well established that prostate cancer growth depends on androgen receptor (AR) signaling. Dr. Giannakakou and her team reported that AR traffics on microtubules to translocate to the nucleus and that taxane treatment inhibits AR nuclear accumulation and activity. In addition, they showed that two clinically prevalent androgen receptor splice variants that accumulate in CRPC determine taxane sensitivity.
More recently they also showed that ERG overexpression– due to the common TMPRSS 2:ERG fusion event which occurs in 50% of PC patients–is associated with decreased sensitivity to taxanes in vitro and in vivo (Nature Communications, 2014).
The ultimate goal is to develop better-targeted therapies for the treatment of cancer patients. Dr. Giannakakou will act as a co-Director for the Developmental Research Program of the WCM Prostate Spore. Dr. Giannakakou has extensive expertise in prostate cancer research.
Also, she participated in team projects such as in a PO1 (Lung Cancer, project leader); a SPORE (Head and Neck Cancer, co-investigator and DRP reviewer); and in an U54 (Nanotechnology and biomarker for personalized oncology, as a co-leader).