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Update on systemic therapy for colorectal cancer: biologics take sides.

ABSTRACT: Over the last decade, progress in the management of metastatic colorectal cancer (CRC) has focused on the development of biologic therapy in addition to the back bone of combination chemotherapy. Anti-epidermal growth factor receptor (EGFR) antibodies and agents targeting angiogenesis are widely used in the clinic, and more recently, in a subset of patients with mismatch repair (MMR) deficient cancer, immunotherapy with immune check point inhibitors have been integrated into clinical practice. The major challenge with the use of these biologic therapies is determining predictive biomarkers to optimize patient selection. In this review, we discuss the most recent updates in the use of biologic therapy in CRC. We review data on the role of primary tumor location (PTL) (sidedness) as predictive biomarker and recent advances in treatment of CRC with BRAF mutation.

SUBMITTER: Gbolahan O

PROVIDER: S-EPMC6414333 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Update on systemic therapy for colorectal cancer: biologics take sides.

Gbolahan Olumide O O'Neil Bert B

Translational gastroenterology and hepatology 20190213

Over the last decade, progress in the management of metastatic colorectal cancer (CRC) has focused on the development of biologic therapy in addition to the back bone of combination chemotherapy. Anti-epidermal growth factor receptor (EGFR) antibodies and agents targeting angiogenesis are widely used in the clinic, and more recently, in a subset of patients with mismatch repair (MMR) deficient cancer, immunotherapy with immune check point inhibitors have been integrated into clinical practice. T ...[more]

PMID: 30976712

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Project description:Colorectal cancer (CRC) remains as one of the most common cause of worldwide cancer morbidity and mortality. Improvements in surgical modalities and adjuvant chemotherapy have increased the cure rates in early stage disease, but a significant portion of the patients will develop recurrence or advanced disease. The efficacy of chemotherapy of recurrence and advanced CRC has improved significantly over the last decade. Previously, the historical drug 5-fluorouracil was used as single chemotherapeutic agent. Now with the addition of other drugs such as capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, vemurafenib, and dabrafenib, the median survival of patients with advanced CRC has significantly improved from less than a year to the current standard of almost 2 years. However, the side effects of systemic therapy such as toxicity may cause fatal complications and have a major consequences on the patients' quality of life. Hence, there is an urgent need for key biomarkers which will enable the selection of optimal drug singly or in combination for an individual patient. The application of personalized therapy based on DNA testing could aid the clinicians in providing the most effective chemotherapy agents and dose modifications for each patient. Yet, some of the current findings are controversial and the evidences are conflicting. This review aims at summarizing the current state of knowledge about germline pharmacogenomics DNA variants that are currently used to guide therapeutic decisions and variants that have the potential to be clinically useful in the future. In addition, current updates on germline variants conferring treatment sensitivity, drug resistance to existing chemotherapy agents and variants affecting prognosis and survival will also be emphasized. Different alteration in the same gene might confer resistance or enhanced sensitivity; and while most of other published reviews generally stated only the gene name and codon location, we will specifically discuss the exact variants to offer more accurate information in this mini review.

Dataset Information

Update on systemic therapy for colorectal cancer: biologics take sides.

Publications

Update on systemic therapy for colorectal cancer: biologics take sides.

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