A Brief Review on Chemoresistance; Targeting Cancer Stem Cells as an Alternative Approach.

The acquisition of resistance to traditional chemotherapy and the chemoresistant metastatic relapse of minimal residual disease both play a key role in the treatment failure and poor prognosis of cancer. Understanding how cancer cells overcome chemotherapy-induced cell death is critical to improve patient survival rate. Here, we briefly describe the technical approach directed at obtaining chemoresistant cell lines and we will focus on the main defense mechanisms against common chemotherapy triggers by tumor cells. Such as, the alteration of drug influx/efflux, the enhancement of drug metabolic neutralization, the improvement of DNA-repair mechanisms, the inhibition of apoptosis-related cell death, and the role of p53 and reactive oxygen species (ROS) levels in chemoresistance. Furthermore, we will focus on cancer stem cells (CSCs), the cell population that subsists after chemotherapy, increasing drug resistance by different processes such as epithelial-mesenchymal transition (EMT), an enhanced DNA repair machinery, and the capacity to avoid apoptosis mediated by BCL2 family proteins, such as BCL-XL, and the flexibility of their metabolism. Finally, we will review the latest approaches aimed at decreasing CSCs. Nevertheless, the development of long-term therapies to manage and control CSCs populations within the tumors is still necessary.

Trypsinogen and chymotrypsinogen: potent anti-tumor agents.

Introduction: Trypsinogen and chymotrypsinogen have been used clinically in tissue repair due to their ability to resolve inflammatory symptoms. Recently, novel evidence has supported the anti-tumourigenic potential of a mixture of trypsinogen and chymotrypsinogen.Areas covered: First, we analyze the structure of these proteases and the effects of pancreatic proteinases on tissue repair, inflammation and the immune system. Second, we summarize studies that provided evidence of the effects of pancreatic (pro)enzymes on tumor cells both in vitro and in vivo and some successful clinical applications of pancreatic (pro)enzymes. Finally, we study pancreatic (pro)enzymes potential molecular targets, such as the proteinase-activated receptors (PARs).Expert opinion: This novel therapy has been shown to have effective antitumor effects. Treatment with these (pro) enzymes sensitizes Cancer Stem Cells (CSCs) which may allow chemotherapy and radiotherapy to be more effective, which could positively affect the recovery of cancer patients.