Inherent and acquired anticancer drug resistance phenomena are major impediments towards curative chemotherapy of various human malignancies. Among anticancer drugs is the group of folic acid antagonists known as antifolates. Hence, the primary focus of our lab is identification and characterization of novel molecular mechanisms of antifolate anticancer drug resistance in multiple cancer cell lines and in cancer patients. These include for example alterations (i.e. loss of function) in transcription factors involved in the down-regulation of gene expression of the reduced folate carrier (RFC), the primary influx transporter for antifolates. Major efforts are also invested in the elucidation of the mechanisms of antifolate resistance that are associated with the overexpression of multidrug resistance (MDR) efflux transporters of the ABC superfamily including MRP1 (ABCC1) through MRP6 (ABBCC6) as well as BCRP (ABCG2). Furthermore, we are also exploring the role of influx and efflux transporters as well as folate-dependent enzymes involved in the maintenance of intracellular folate homeostasis and its affect on antifolate resistance. Gaining a profound understanding of the multiple molecular mechanisms of anticancer drug resistance in individual cancer patients should pave the way for the reversal of drug resistance as well as tailor-made chemotherapy to individual cancer patients.
Lab members:
Yehuda G. Assaraf, (Principal Investigator).
Dr. Stavit Drori,
(Post-doc)
Dr. Michal Stark, (Post-doc).
Eran Bram, (PhD. student).
Nitzan Drucker- Gonen (PhD. student)
Vicky Goler-Baron (PhD. student)
Inbal Lasri, (M.Sc. student).
Yamit Bney-Moshe, (B.Sc. student).
Shachar Raz, (B.Sc. student).
Bluma Berman, (Lab technician).
