Abstract
Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-xL and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer.
Highlights
Pancreatic cancer is one of the most malignant and aggressive types of cancer in humans and carries a very poor prognosis
This review will discuss the facts about apoptotic pathways and the deregulation of apoptotic proteins in pancreatic cancer to demonstrate the correlation between disease occurrence and defects in apoptotic mechanisms
The intrinsic pathway can be initiated in mitochondria by stress stimuli and is regulated by the balance of the action of pro-apoptotic and anti-apoptotic Bcl-2 protein family members. (C) Inhibitor of apoptosis proteins (IAPs) and other signal transduction molecules are able to diminish the effect of caspase 8 activation
Summary
Pancreatic cancer is one of the most malignant and aggressive types of cancer in humans and carries a very poor prognosis. The delayed appearance of symptoms causes a late diagnosis; as a result, roughly 85% of patients show an organ overlapping growth of the tumor when the disease is first discovered, and only the remaining 15% of patients have an opportunity for curative surgical treatment. Despite improvements made in surgical techniques and pre- and postoperative care, less progress has been seen in improving the survival of patients with this type of cancer [3]. Uncontrolled proliferation, a high metastatic potential and resistance to most adjuvant therapies contribute to the very poor prognosis of this disease. Tumor development and progress of PDACs as well as resistance to most oncology therapies involve the absence of a reaction to apoptotic stimuli [4]. This review will discuss the facts about apoptotic pathways and the deregulation of apoptotic proteins in pancreatic cancer to demonstrate the correlation between disease occurrence and defects in apoptotic mechanisms
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