Dysregulated Signalling Pathways Driving Anticancer Drug Resistance

Abstract

One of the leading causes of death worldwide, in both men and women, is cancer. Despite the significant development in therapeutic strategies, the inevitable emergence of drug resistance limits the success and impedes the curative outcome. Intrinsic and acquired resistance are common mechanisms responsible for cancer relapse. Several factors crucially regulate tumourigenesis and resistance, including physical barriers, tumour microenvironment (TME), heterogeneity, genetic and epigenetic alterations, the immune system, tumour burden, growth kinetics and undruggable targets. Moreover, transforming growth factor-beta (TGF-β), Notch, epidermal growth factor receptor (EGFR), integrin-extracellular matrix (ECM), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), wingless-related integration site (Wnt/β-catenin), Janus kinase/signal transducers and activators of transcription (JAK/STAT) and RAS/RAF/mitogen-activated protein kinase (MAPK) signalling pathways are some of the key players that have a pivotal role in drug resistance mechanisms. To guide future cancer treatments and improve results, a deeper comprehension of drug resistance pathways is necessary. This review covers both intrinsic and acquired resistance and gives a comprehensive overview of recent research on mechanisms that enable cancer cells to bypass barriers put up by treatments, and, like “satellite navigation”, find alternative routes by which to carry on their “journey” to cancer progression.

The characteristics and the multiple functions of integrin β1 in human cancers

“…In this review, we elucidate our understanding of the characteristics, ligands, signaling pathways and biological functions of integrin β1, which can be classified into four receptors; namely, the RGD-binding receptors, leukocyte-specific receptors, laminin-binding receptors and collagen binding receptors according to the specificity of the ligands [ 102 ]. The current investigation provides evidence that the integrin β1–ECM interaction activates FAK, MAPK, PI3K-AKT, and other pathways for tumor growth, metastasis, invasion and angiogenesis [ 103 ]. Moreover, integrin β1 also confers tumor cell chemoresistance, radioresistance, and immunoresistance [ 104 ].…”

Chemotherapy Resistance in Cancer: Mechanism and Roadmap to Evade Exploring Apoptosis

“…are the major anti-apoptotic proteins (Chota et al, 2021). However, a down regulation or reduced expression of pro-apoptotic proteins and an enhanced activity and/or over-expression of anti-apoptotic proteins have been observed in the case of drug resistant tumors (Bou Antoun & Chioni, 2023). Most of the chemo drugs induce mitochondrial outer membrane potential (MOMP) that lead to the release of cytochrome c into the cytoplasm.…”

The role of circRNAs in regulation of drug resistance in ovarian cancer

“…Acquired resistance develops over time after tumor cells adapt to the therapy, leading to therapy failure ( Ye et al, 2023 ). The potential mechanisms of drug resistance include genetic mutations, activation of alternative pathways, efflux pumps, enhanced DNA repair capabilities, tumor microenvironment change ( Liu et al, 2022b ; Bou Antoun and Chioni, 2023 ). Epigenetic changes, including ncRNAs, have been reported to affect gene expression and contribute to drug resistance ( Jiang et al, 2020 ; Xie et al, 2022 ).…”