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Targeted Therapy in Metastatic Colorectal Cancer: Current Standards and Novel Agents in Review

  • Systemic Therapies in Colorectal Cancer (SM Kazmi, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Purpose of Review

Treatment options for patients with metastatic colorectal cancer continue to advance as the therapeutic implications of the molecular subtypes of this disease are becoming better understood. DNA sequencing and mismatch repair assessment are now standard of care analyses for patients with metastatic colorectal cancer This review describes important aspects of the biology of the clinically relevant molecular subtypes of colorectal cancer based on the current standard of care testing. In addition, the clinical treatment strategies available now and potentially in the future for these colorectal cancer subtypes are discussed.

Recent Findings

Currently, for metastatic colorectal cancer, standard of care molecular testing is done for mutations in exons 2, 3, and 4 of KRAS and NRAS, and BRAF V600E. Testing for mismatch repair (MMR) deficiency/microsatellite instability (MSI) status is also done. These aberrations are well known to change the clinical prognosis and guide patients’ treatment strategies. Additionally, three new subtypes have emerged: PIK3CAmut, HER2 amplified, and NTRK fusions. With the addition of these emerging subtypes, tumor heterogeneity further validates the need to examine mCRC as a heterogeneous disease. Here, we present recent exciting data from translational research and clinical trials exhibiting possible distinct treatment strategies for these different subtypes.

Summary

Altogether, these data show promising treatment strategies for many of these well-known and emerging subtypes of mCRC. In addition, these also give better clinical prognostic and predictive information. We believe that as molecular testing expands, PIK3CA mutation, HER2 amplification, and NTRK fusion molecular testing will be included in standard of care analyses. This incorporation of testing in clinical practice will generate further information regarding prognostic and therapeutic options for these and other CRC subtypes in the future.

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Financial Support

This project was supported by P30 CA014520 (Core Grant, University of Wisconsin Carbone Cancer Center).

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA

    Rebecca A. DeStefanis, Jeremy D. Kratz, Philip B. Emmerich & Dustin A. Deming

  2. University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA

    Dustin A. Deming

  3. McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6507 Wisconsin Institutes for Medical Research, 1111 Highland Ave, Madison, WI, 53705, USA

    Dustin A. Deming

Authors
  1. Rebecca A. DeStefanis
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  2. Jeremy D. Kratz
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  3. Philip B. Emmerich
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  4. Dustin A. Deming
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Corresponding author

Correspondence to Dustin A. Deming.

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Conflict of Interest

Rebecca A. DeStefanis declares that she has no conflict of interest.

Jeremy D. Kratz declares that he has no conflict of interest.

Philip B. Emmerich declares that he has no conflict of interest.

Dustin A. Deming has received clinical trial funding from Merck, and has received compensation from Bristol-Myers Squibb, Genentech, Bayer, and Array Pharmaceuticals for service on advisory boards.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Systemic Therapies in Colorectal Cancer

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DeStefanis, R.A., Kratz, J.D., Emmerich, P.B. et al. Targeted Therapy in Metastatic Colorectal Cancer: Current Standards and Novel Agents in Review. Curr Colorectal Cancer Rep 15, 61–69 (2019). https://doi.org/10.1007/s11888-019-00430-6

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