Beta-Tubulins: Mediators of Chemoresistance in Pancreatic Cancer (#233)
Pancreatic cancer is a devastating disease and despite aggressive treatment strategies, overall 5-year survival rates are less than 5%. One of the major reasons for the poor clinical outcome of pancreatic cancer is the well-known resistance to chemotherapeutic agents. There is mounting evidence to suggest that the tubulin/microtubule network is altered in cancer cells resistant to chemotherapy. Strong data from our laboratory shows that both βIII- and βIVb-tubulin are significantly increased in pancreatic cancer cells and human pancreatic adenocarcinoma tissue. Importantly, silencing βIII- or βIVb-tubulin using siRNA in pancreatic cancer cells sensitises the cells to gemcitabine (first-line treatment of pancreatic cancer), as well as tubulin-binding agents (TBAs). We also have data to suggest that βIII-tubulin may be a promising drug target without the necessity for chemotherapy. Therefore, we hypothesise that βIII- and βIVb-tubulin play an important role in regulating drug resistance in pancreatic cancer and elucidating their function in mediating drug sensitivity and tumour growth may improve treatment strategies for this disease.