Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 30;10(5):1035.
doi: 10.3390/biomedicines10051035.

Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy

Gerardo Rosati  1 , Giuseppe Aprile  2 , Alfredo Colombo  3 , Stefano Cordio  4 , Marianna Giampaglia  1 , Alessandro Cappetta  2 , Concetta Maria Porretto  3 , Alfonso De Stefano  5 , Domenico Bilancia  1 , Antonio Avallone  5
Affiliations
Review

Colorectal Cancer Heterogeneity and the Impact on Precision Medicine and Therapy Efficacy

Gerardo Rosati et al. Biomedicines. .

Abstract

Novel targeted therapies for metastatic colorectal cancer are needed to personalize treatments by guiding specific biomarkers selected on the genetic profile of patients. RAS and BRAF inhibitors have been developed for patients who become unresponsive to standard therapies. Sotorasib and adagrasib showed promising results in phase I/II basket trial and a phase III trial was planned with a combination of these RAS inhibitors and anti-EGFR monoclonal antibodies. Encorafenib and binimetinib were administered in phase II clinical trials for BRAF mutated patients. Pembrolizumab is now recommended in patients exhibiting microsatellite instability. Larotrectinib and entrectinib showed a fast and durable response with few and reversible adverse events in cases with NTRK fusions. Trastuzumab and trastuzumab deruxtecan exhibited promising and durable activity in HER-2-positive patients. In this review, the reasons for an extension of the molecular profile of patients were assessed and placed in the context of the advancements in the understanding of genetics. We highlight the differential effect of new targeted therapies through an ever-deeper characterization of tumor tissue. An overview of ongoing clinical trials is also provided.

Keywords: RAS and BRAF inhibitors; TRK inhibitors; anti-HER-2; immunotherapy; metastatic colorectal cancer; precision medicine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the writing of the manuscript or in the decision to publish the results.

Figures

Figure 1
Figure 1
Therapeutic targets in metastatic colorectal cancer. The main oncogenic drivers. Signaling pathways and their prevalence in patients with metastatic colorectal cancer.
See this image and copyright information in PMC

References

    1. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer statistics, 2021. CA Cancer J. Clin. 2021;71:7–33. doi: 10.3322/caac.21654. - DOI - PubMed
    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Dekker E., Tanis P.J., Vleugels J.L.A., Kasi P.M., Wallace M.B. Colorectal cancer. Lancet. 2019;394:1467–1480. doi: 10.1016/S0140-6736(19)32319-0. - DOI - PubMed
    1. Koehler A., Bataille F., Schmid C., Ruemmele P., Waldeck A., Blaszyk H., Hartmann A., Hofstaedter F., Dietmaier W. Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stage. J. Pathol. 2004;204:65–74. doi: 10.1002/path.1606. - DOI - PubMed
    1. Sepulveda A.R., Hamilton S.R., Allegra C.J., Grody W., Cushman-Vokoun A.M., Funkhouser W.K., Kopetz S.E., Lieu C., Lindor N.M., Minsky B.D., et al. Molecular biomarkers for the evaluation of colorectal cancer: Guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J. Clin. Oncol. 2017;35:1453–1486. doi: 10.1200/JCO.2016.71.9807. - DOI - PubMed