Dataset Information

Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives.

ABSTRACT: Substantial improvements have characterized the systemic treatment of metastatic colorectal cancer (mCRC) over the past 20 years. Besides strong evidence that supports the use of RAS and BRAF status as prognostic and predictive indicators of disease and response, novel technologies have made possible the incorporation of emerging biomarkers for the management of mCRC. On one hand, the discovery of point mutations, amplifications, fusions, and gene expression profiles highlights the genomic and dynamic complexity of CRC. On the other, such discoveries are leading to newer biomarker-driven strategies that add to existing anti-epidermal growth factor receptor (EGFR) and anti-angiogenic approaches. In addition, the availability of a wide molecular profiling has relevant implications for patient prognosis and treatment benefits. Here, we will review the molecular underpinnings and clinical data supporting novel targeted treatments under development for refractory mCRC harboring BRAF mutations, KRAS G12C mutations, HER2 amplification, and less common molecular alterations, such as the re-arrangements of NTRK, ALK, and ROS1. Additionally, we will discuss novel strategies driving the rechallenge of EGFR antibodies and the incorporation of newer anti-angiogenic agents in the therapeutic armamentarium.

SUBMITTER: Personeni N

PROVIDER: S-EPMC8472765 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives.

Personeni Nicola N Smiroldo Valeria V Giunta Emilio Francesco EF Prete Maria Giuseppina MG Rimassa Lorenza L Bregni Giacomo G Sclafani Francesco F

Cancers 20210907 18

Substantial improvements have characterized the systemic treatment of metastatic colorectal cancer (mCRC) over the past 20 years. Besides strong evidence that supports the use of RAS and BRAF status as prognostic and predictive indicators of disease and response, novel technologies have made possible the incorporation of emerging biomarkers for the management of mCRC. On one hand, the discovery of point mutations, amplifications, fusions, and gene expression profiles highlights the genomic and d ...[more]

PMID: 34572729

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Project description:Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli. CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%); inherited (5%) and familial (25%). The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53), and mutations; in particular, genes such as c-MYC, KRAS, BRAF, PIK3CA, PTEN, SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined with monoclonal antibodies or proteins against vascular endothelial growth factor (VEGF) and epidermal growth receptor (EGFR). Besides traditional chemotherapy, alternative therapies (such as agarose tumour macrobeads, anti-inflammatory drugs, probiotics, and gold-based drugs) are currently being studied to increase treatment effectiveness and reduce side effects.

Dataset Information

Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives.

Publications

Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives.

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