Regulation of signal transduction pathways in colorectal cancer: implications for therapeutic resistance

Abstract

Resistance to anti-cancer treatments is a critical and widespread health issue that has brought serious impacts on lives, the economy and public policies. Mounting research has suggested that a selected spectrum of patients with advanced colorectal cancer (CRC) tend to respond poorly to both chemotherapeutic and targeted therapeutic regimens. Drug resistance in tumours can occur in an intrinsic or acquired manner, rendering cancer cells insensitive to the treatment of anti-cancer therapies. Multiple factors have been associated with drug resistance. The most well-established factors are the emergence of cancer stem cell-like properties and overexpression of ABC transporters that mediate drug efflux. Besides, there is emerging evidence that signalling pathways that modulate cell survival and drug metabolism play major roles in the maintenance of multidrug resistance in CRC. This article reviews drug resistance in CRC as a result of alterations in the MAPK, PI3K/PKB, Wnt/β-catenin and Notch pathways.

Synergistic Approach of Antibody‐Photosensitizer Conjugate Independent of KRAS‐Mutation and Its Downstream Blockade Pathway in Colorectal Cancer

“…KRAS-mutated CRC cells exhibit resistance to anti-EGFR therapies such as CTX, owing to the inability of mutant KRAS proteins to switch between activated and inactivated conformations. [38,39] The activation of downstream signaling pathways of EGFR leads to the growth and proliferation of cancer cells by continuously activating signaling proteins such as mitogen-activated protein kinase (MAPK/ERK) and phosphoinositide 3-kinase (PI3K/AKT), ultimately promoting treatment resistance (Figure 3A). [40,41] To investigate the effects of CMPXC-mediated PDT on the signaling pathways, the expression of proteins associated with the MAPK/ERK and PI3K/AKT pathways was measured through immunoblot analysis at different time points (1, 2, and 3 d) after treatment with CTX alone and CMPXC.…”

Diatom-Based Nanomedicine for Colorectal Cancer Treatment: New Approaches for Old Challenges

“…Targeted approaches involve the use of a drug precisely targeted to an “invader” (e.g., proteins, nucleic acids) whose function (or dysfunction) promotes cancer cell proliferation and migration [ 61 ]. Turning off or regulating a dominant signal in CRC with the drug may increase tumor cell killing and decrease off-target effects, such as epithelial cell damage [ 62 ]. For example, almost 40% of cases of metastatic CRC are caused by mutations in members of the RAS superfamily [ 63 ], resulting in increased proliferation, angiogenesis, and alterations of cell metabolism.…”

A recent update on small‐molecule kinase inhibitors for targeted cancer therapy and their therapeutic insights from mass spectrometry‐based proteomic analysis

“…Resistance to anti‐cancer drugs including KIs often causes failure in treatment. Dysregulation of signalling pathways is among the common mechanism that contributes to drug resistance [75]. Comprehensive analysis of the phoshoproteome is useful for deciphering the underlying adaptive mechanism and remodelled signalling networks associated with such resistance.…”