Failure of Pancreatic Cancer Chemotherapy: Consequences of Drug Resistance Mechanisms

Pancreatic cancer is one of the most lethal forms of cancer and it is estimated that there will be about 44,000 new cases in US in the year 2011. With 37,600 estimated deaths in 2011, pancreatic cancer is the fourth leading cause of cancer related deaths in US (American Cancer Society, 2011). In spite of numerous efforts, the 5-year survival rate for pancreatic cancer has not improved much for the last few decades. The suggested reasons for low survival among the pancreatic cancer patients include late disease diagnosis, highly invasive and metastatic nature, lack of effective therapies, and acquisition of resistant characteristics (American cancer Society 2007; Moore, et al., 2003; NIH 2007). Only two drugs – gemcitabine (GEM) and 5fluorouracil (5FU) – have been shown to improve the survival of patients consistently. 5FU was the first drug to be approved as adjuvant therapy for pancreatic cancer (Kalser and Ellenberg, 1985; Moertel, et al., 1981). Since then, GEM has been used as the first line chemotherapeutic drug for pancreatic cancer. However, GEM treatment does not always provide extended survival benefits. A study found that in post-operative patients, GEM treatment increased the survival by merely 6 months (Shore, et al., 2003). 5FU is also widely used as an adjuvant and neoadjuvant chemotherapeutic agent to treat pancreatic cancers (Ahlgren, 1996; Blaszkowsky, 1998; Snady, et al., 2000).