Proteomic investigations into resistance in colorectal cancer

ABSTRACT

Introduction: Despite advances in screening and treatment options, colorectal cancer (CRC) remains one of the most prevalent and lethal cancer subtypes. Resistance to cytotoxic or targeted therapy has remained a constant challenge to the treatment and long-term management of patients, attracting intense worldwide investigation since the 1950s. Through extensive investigations into the proteomic mechanisms and functions that convey resistance to therapy/s, researchers have become able to implicate alterations in several signaling pathways that provide and sustain resistance to treatment.

Areas covered: In this review, we summarize how protein alterations are associated with resistance to therapy, with particular emphasis on CRC. An overview of the mechanisms of therapeutic resistance is described, highlighting recent studies which endeavor to elucidate the proteomic changes that are associated with the acquisition and promulgation of therapeutic resistance.

Expert opinion: While cancers such as CRC have been intensively studied for decades, unresponsiveness and the resistance to therapy remain critical obstacles in the treatment of patients. Due to the inherent biological and clinical heterogeneity of individual CRCs, proteomic methods stand to become powerful tools to provide biological insights that may guide therapeutic strategies with the ultimate goal of refining emergent immunotherapeutic treatments.

Graphical abstract

KEYWORDS:

• Chemotherapy
• colorectal cancer
• cytotoxicity
• proteomics
• resistance

Article highlights

• The onset of resistance to therapy is a common, leading and direct cause of CRC patient mortality

• Despite an impressive array of potential therapies, mCRCs possess the ability to evolve mechanisms of resistance to their cytostatic/cytotoxic activities

• The ability to diagnose resistance to a particular treatment regimen/s would enable the proscription of more appropriate drugs and ensure that these costly therapies are being delivered to patients who are more likely to respond

• Numerous studies into CRC resistance have been performed, though outcomes and reproducibility is hampered by patient/tumoural heterogeneity

• ML-based multi-omic approaches may offer the best means of tumoural classification and guidance of therapy design

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

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Funding

This manuscript received no funding for any stage of preparation, review or submission.