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Precision treatment in colorectal cancer: Now and the future.

ABSTRACT: Until recently, a one-drug-fits-all model was applied to every patient diagnosed with the same condition. But not every condition is the same, and this has led to many cases of ineffective treatment. Pharmacogenetics is increasingly used to stratify patients for precision medicine treatments, for instance, the UGT1A1*28 polymorphism as a dosage indicator for the use of irinotecan as well as epidermal growth factor receptor (EGFR) immunohistochemistry and KRAS Proto-Oncogene (KRAS) exon 2 mutation tests for determining the likelihood of treatment response to cetuximab or panitumumab treatment in metastatic colorectal cancer (CRC). The other molecular subtypes, such as KRAS exon 3/4, B-Raf Proto-Oncogene, NRAF, PIK3CA, and PETN, were also reported as potential new pharmacogenetic targets for the current and the newly discovered anticancer drugs. In addition to next-generation sequencing (NGS), primary tumor cells for in vivo and in vitro drug screening, imaging biomarker 3'-Deoxy-3'-18F-fluorothymidine positron emission tomography, and circulating tumor DNA (ctDNA) detection methods are being developed and may represent the future direction of precision medicine. This review will discuss the current environment of precision medicine, including clinically approved targeted therapies, the latest potential therapeutic agents, and the ongoing pharmacogenetic trials for CRC patients.

SUBMITTER: Yau TO

PROVIDER: S-EPMC6788378 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Precision treatment in colorectal cancer: Now and the future.

Yau Tung On TO

JGH open : an open access journal of gastroenterology and hepatology 20190208 5

Until recently, a one-drug-fits-all model was applied to every patient diagnosed with the same condition. But not every condition is the same, and this has led to many cases of ineffective treatment. Pharmacogenetics is increasingly used to stratify patients for precision medicine treatments, for instance, the UGT1A1*28 polymorphism as a dosage indicator for the use of irinotecan as well as epidermal growth factor receptor (EGFR) immunohistochemistry and KRAS Proto-Oncogene (<i>KRAS</i>) exon 2 ...[more]

PMID: 31633039

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Project description:Background: Colorectal cancer is one of the most frequent neoplasms worldwide, and the majority of patients are diagnosed in advanced stages. Metastatic colorectal cancer (mCRC) harbors several mutations with different prognostic and predictive values; KRAS, NRAS, and BRAF mutations are the best known. Indeed, RAS and BRAF molecular status are associated with a different response to monoclonal antibodies (Anti-epidermal growth factor receptor and anti-vascular endothelial growth factor receptor agents), which are usually added to chemotherapy in first-line, and thus allow to select the optimal therapy for patients with mCRC. Furthermore, sidedness is an important predictive and prognostic factor in mCRC, which is explained by the different molecular profile of left and right-sided tumors. Recently, microsatellite instability-high has emerged as a predictive factor of response and survival from immune checkpoint inhibitors in mCRC. Finally, several other alterations have been described in lower frequencies, such as human epidermal growth factor receptor-2 overexpression/amplification, PIK3CA pathway alterations, phosphatase and tension homolog loss, and hepatocyte growth factor/mesenchymal-epithelial transition factor pathway dysregulation, with several targeted therapies already demonstrating activity or being tested in currently ongoing clinical trials. Aim: To review the importance of studying the predictive and prognostic roles of the molecular profile of mCRC, the changes occurred in recent years and how they would potentially change in the near future, to guide physicians in treatment decisions. Relevance for Patients: Today, several different therapeutic options can be offered to patients in the first-line setting of mCRC. Therapies at present approved or under investigation in clinical trials will be thoroughly reviewed, with special emphasis on the molecular rationale behind them. Understanding the molecular status, resistance mechanisms and potential new druggable targets may allow physicians to choose the best therapeutic option in the first-line mCRC.

Dataset Information

Precision treatment in colorectal cancer: Now and the future.

Publications

Precision treatment in colorectal cancer: Now and the future.

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