Abstract
Despite substantial progress in cancer therapy, colorectal cancer (CRC) is still the third leading cause of cancer death worldwide, mainly due to the acquisition of resistance and disease recurrence in patients. Growing evidence indicates that deregulation of hormone signaling pathways and their cross-talk with other signaling cascades inside CRC cells may have an impact on therapy resistance. MicroRNAs (miRNAs) are small conserved non-coding RNAs thatfunction as negative regulators in many gene expression processes. Key studies have identified miRNA alterations in cancer progression and drug resistance. In this review, we provide a comprehensive overview and assessment of miRNAs role in hormone signaling pathways in CRC drug resistance and their potential as future targets for overcoming resistance to treatment.
Highlights
Despite substantial progress in cancer therapy, colorectal cancer (CRC) is still the third leading cause of cancer death worldwide, mainly due to the acquisition of resistance and disease recurrence in patients
The problem of ineffectiveness of therapy/drug resistance could be due to the considerable heterogeneity of CRC, which can be categorized into three main groups: (1) Chromosomal Instability (CIN) with ~65–85% of incidence, (2) Microsatellite Instability (MSI) present in ~12–15% of patients, and (3) CpG Island Methylator phenotype (CIMP) in
CRC treatment indicates the existenceofofresistance complex genetic, epigenetic, and targeted therapies for treatment indicates the existence of complex genetic, epand metabolic alterations leading to impaired drug sensitivity and multiple mechanisms igenetic, and metabolic alterations leading to impaired drug sensitivity and multiple for drug resistance. 5-FU remains the first-line therapy in CRC, but new strategies have mechanisms forimprove drug resistance
Summary
Colorectal cancer (CRC) is the third cause of cancer-related death worldwide after lung and breast carcinomas [1]. MSI is associated with mismatch repair deficiency (MMR-D), which arises from the loss of function of mismatch repair (MMR) genes [19] Such aberrant expressions are harnessed by cancer for immunotherapy escape: MSI-H/MMR-D CRC patients showed multiple genetic alterations related to immune response, in particular in WNT/β-catenin signaling [20], whose activation reduces the efficacy of immune checkpoint blockade therapy [20]. The demethylating agent 20 -deoxy-5-azacitidine (DAC), an inhibitor of DNMT, allowed the reactivation of MLH1, whose repression is associated with resistance to various drugs, including cisplatin and epirubicin This reactivation has, granted an increase in the effectiveness of chemotherapy in CRC cells [27]. Apoptosis escape: many drugs work by activating apoptotic pathways in cancer cells; resistant CRC cells increase expression of anti-apoptotic proteins (Bcl-2, Bcl-xL) and decrease expression of pro-apoptotic proteins (BAD, BAX, and Fas) promoting cell survival
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
