Global perspectives on Pancreatic Cancer Treatment

Abstract

Pancreatic cancer (PDAC) remains one of the most deadly cancers. Currently, PDAC is the 4th cause of cancer related deaths and is expected to rise to the second position in about 10 years. Most patients with PDAC present with metastatic disease for which no curative treatment exist. Furthermore, up to 70 % who present with local disease and undergo potentially curative resection followed by chemotherapy relapse. In addition, those patients who present with locally advanced disease also have a dismal prognosis with median survival in the 12 months range. Recent advances include the development and approval of more effective chemotherapy regimens such as FOLFIRINOX and Gemcitabine-Nab-paclitaxel for patients with newly diagnosed advanced disease, the role of MM398 in the second line setting, lack of benefit from adding radiation therapy to chemotherapy in patients with locally advanced disease, role of DPC4 mutations as a marker or oligometastatic disease, higher synergistic effects of capecitabine versus gemcitabine in combination with radiation therapy, and role of S1 in the adjuvant setting. Despite these poor results, important advances have been made recently in the understanding of the biology of PDAC. Several studies have deciphered the mutational landscape of PDAC to show that it is a highly complex, heterogeneous and unstable disease. While most of the mutations discovered are not actionable, certain subgroups of patients with genotypes amenable to specific treatments are emerging such as for example patients with DNA damage repair pathway alterations. In addition, there is great interest to target the PDAC stroma both as a specific therapeutic option but also as a mechanism to synergize with immune therapy strategies. Finally, strategies to target the cancer stem cell will be presented. Laboratory studies have shown the presence of a small percentage of cells in PDA tumours with stem properties. These cells can be identified by membrane markers and are considered to be resistant to chemotherapy and radiotherapy. It is possible, that CSC is responsible for cancer failure after definitive chemotherapy and radiotherapy and there is significant interest in developing agents to selectively eliminate these cells.