Chemoresistance in pancreatic cancer: Emerging concepts

Abstract

Abstract. Pancreatic cancer is one of the most lethal types of cancer in the world. The incidence of pancreatic cancer increases each year with no significant decrease in mortality. Pancreatic cancer is a complex disease, and this complexity is partly attributed to late diagnosis, an aggressive phenotype, environmental factors and lack of effective treatment options. Surgical resection followed by adjuvant chemotherapy is the treatment of choice for early stage cancer, whereas gemcitabine is the standard first line therapy for patients with advanced stage disease. Treatment regimens comprising folinic acid, 5-fluorouracil, irinotecan, oxaliplatin and nab-paclitaxel have demonstrated modest effects in improving median survival rates. A number of other chemotherapeutics are currently undergoing clinical trials as components of combination therapies with gemcitabine. An increasing number of novel molecular targets and cellular pathways are being identified, which highlights the complexity of this disease. The development of chemoresistance to gemcitabine is multifactorial and there exists an interplay between pancreatic cancer cells, the tumor microenvironment and cancer stem cells. These components appear to be governed by a complex network of non-coding RNAs such as micro RNAs and long non-coding RNAs. In the present study, studies describing previous research on the understanding of the factors associated with the development of chemoresistance to gemcitabine in pancreatic cancer are reviewed. A comprehensive understanding of the multiple pathways of chemoresistance is key to develop next generation therapeutics to pancreatic cancer.

Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

“…Adjuvant chemotherapy is often given after surgery for certain types of cancer, such as pancreatic, colorectal, and breast cancer, to improve prognosis by reducing the potential for recurrence and metastasis [96][97][98][99] . However, in some cancers, including intrahepatic cholangiocarcinoma (ICC), the prognosis of patients is extremely poor because the recurrence rate after curative operation is very high and there is no standard adjuvant setting.…”

Hypoxia alters the release and size distribution of extracellular vesicles in pancreatic cancer cells to support their adaptive survival

“…8 As a result, PC cells encounter moderate to extreme hypoxia during the course of their progression, which alter their cellular and behavioral properties. 3,10,11 However, underlying mechanisms remain poorly understood. 3,10,11 However, underlying mechanisms remain poorly understood.…”

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT‑2 pancreatic cancer mouse model

“…Even if resected, most will eventually metastasize to locations such as the liver or peritoneum (1)(2)(3). Improvements in chemotherapy are necessary to improve the prognosis of pancreatic cancer patients (4). Gemcitabine was approved in the United States in 1996 and is a key drug for patients with pancreatic cancer (5).…”

“…Generally, preclinical drug development examines the effects of the subcutaneous implantation model on tumor regression. Mia-pa-ca-2, Capan-1, and BX-PC-3 are used as models for Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT-2 pancreatic cancer mouse model 1,4 and TAKAYUKI ASAO pancreatic cancer; however, only BX-PC-3 is used as a model for gemcitabine resistance in pancreatic cancer. Our laboratory has not confirmed distant metastasis in models involving subcutaneous implantation of Capan-1 or SUIT-2 cell lines.…”