Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related death in the US, accounting for an estimated 37.000 in 2010 (Jemal et al., 2010). Only about 10-15% of newly diagnosed PDAC are potentially resectable, while the majority of patients present with locally advanced or metastatic cancer. The median survival of non operable patients treated with standard chemotherapy ranges between 3 and 10 months, with less than 20% alive at 1 year (Van Cutsem et al., 2004a). Survival rates have not substantially improved during the past 25 years, and gemcitabine, currently considered as the standard for the treatment of patients with advanced PDAC, only offers a limited advantage over 5-fluorouracil. Moreover, in these patients the tolerance of chemotherapy is often limited, due to the frequent occurence of pain and poor performance status. Given the limited efficacy of conventional chemotherapy, there is an urgent need of new treatment options for this disease. It is now clear that development and progression of PDAC is a complex process involving alterations of a core set of signalling pathways implicated in the regulation of multiple processes such as proliferation, cell cycle, migration, invasion, metastatization, metabolism, angiogenesis and resistance to apoptosis (S. Jones et al., 2008). This chapter will overview the more relevant cellular pathways involved in the development and progression of PDAC, and the results obtained in preclinical models and clinical trials with the use of novel agents specifically targeting them.
New Targets for Therapy in Pancreatic Cancer
TINARI, Nicola;DE TURSI, Michele;GRASSADONIA, Antonino;IACOBELLI, Stefano;NATOLI, Clara
2012-01-01
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related death in the US, accounting for an estimated 37.000 in 2010 (Jemal et al., 2010). Only about 10-15% of newly diagnosed PDAC are potentially resectable, while the majority of patients present with locally advanced or metastatic cancer. The median survival of non operable patients treated with standard chemotherapy ranges between 3 and 10 months, with less than 20% alive at 1 year (Van Cutsem et al., 2004a). Survival rates have not substantially improved during the past 25 years, and gemcitabine, currently considered as the standard for the treatment of patients with advanced PDAC, only offers a limited advantage over 5-fluorouracil. Moreover, in these patients the tolerance of chemotherapy is often limited, due to the frequent occurence of pain and poor performance status. Given the limited efficacy of conventional chemotherapy, there is an urgent need of new treatment options for this disease. It is now clear that development and progression of PDAC is a complex process involving alterations of a core set of signalling pathways implicated in the regulation of multiple processes such as proliferation, cell cycle, migration, invasion, metastatization, metabolism, angiogenesis and resistance to apoptosis (S. Jones et al., 2008). This chapter will overview the more relevant cellular pathways involved in the development and progression of PDAC, and the results obtained in preclinical models and clinical trials with the use of novel agents specifically targeting them.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
