Circulating Tumor DNA as a Novel Biomarker Optimizing Chemotherapy for Colorectal Cancer

doi:10.3390/cancers12061566

Review

. 2020 Jun 13;12(6):1566.

doi: 10.3390/cancers12061566.

Circulating Tumor DNA as a Novel Biomarker Optimizing Chemotherapy for Colorectal Cancer

Hiroki Osumi¹, Eiji Shinozaki¹, Kensei Yamaguchi¹

Affiliations

PMID: 32545750
PMCID: PMC7352651
DOI: 10.3390/cancers12061566

Review

Circulating Tumor DNA as a Novel Biomarker Optimizing Chemotherapy for Colorectal Cancer

Hiroki Osumi et al. Cancers (Basel). 2020.

. 2020 Jun 13;12(6):1566.

doi: 10.3390/cancers12061566.

Authors

Hiroki Osumi¹, Eiji Shinozaki¹, Kensei Yamaguchi¹

Affiliation

¹ Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.

PMID: 32545750
PMCID: PMC7352651
DOI: 10.3390/cancers12061566

Abstract

Liquid biopsy is a minimally invasive method for detecting soluble factors, including circulating tumor DNA (ctDNA), in body fluids. ctDNA carrying tumor-specific genetic or epigenetic alterations is released into circulation from tumor cells. ctDNA in the plasma contains somatic mutations that have occurred in the tumor, and reflects tumor progression and therapeutic effects promptly and accurately. Furthermore, ctDNA is useful for early detection of recurrence and estimation of prognosis and may be utilized for diagnosis and personalized medicine for treatment selection. Thus, in the near future, it will be possible to select the most appropriate treatment based on real-time genetic information using ctDNA.

Keywords: and biomarker; circulating tumor DNA; colorectal cancer; liquid biopsy; minimal residual disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Minimal residual disease (MRD) monitoring and early diagnosis of relapse. Liquid biopsy approaches might be well suited to measuring MRD, as residual tumor components can be detected with high sensitivity. Because MRD-positive patients have higher risk of relapse, early diagnosis of relapse may improve patient outcomes. This figure reflects a representative case of our own original data.

**Figure 2**
Evaluation of chemotherapeutic response and prediction of resistance to chemotherapy. Serial tumor-specific mutation analysis in the blood of patients is useful to monitor response and resistance to molecular targeted drugs. Early decrease of mutant allele after chemotherapy may predict better therapeutic response and clinical outcomes. Furthermore, liquid biopsies can detect the emergence of resistant clones of chemotherapy before radiographic confirmation of disease progression. This figure reflects a representative case of our own original data.

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References

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1. Sawada K., Nakamura Y., Yamanaka T., Kuboki Y., Yamaguchi D., Yuki S., Yoshino T., Komatsu Y., Sakamoto N., Okamoto W., et al. Prognostic and Predictive Value of HER2 Amplification in Patients With Metastatic Colorectal Cancer. Clin. Colorectal Cancer. 2018;17:198–205. doi: 10.1016/j.clcc.2018.05.006. - DOI - PubMed

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[1] Yoshino T., Arnold D., Taniguchi H., Pentheroudakis G., Yamazaki K., Xu R.H., Kim T.W., Ismail F., Tan I.B., Yeh K.H., et al. Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: A JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Ann. Oncol. 2018;29:44–70. doi: 10.1093/annonc/mdx738. - DOI - PubMed

[2] Yoshino T., Arnold D., Taniguchi H., Pentheroudakis G., Yamazaki K., Xu R.H., Kim T.W., Ismail F., Tan I.B., Yeh K.H., et al. Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: A JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Ann. Oncol. 2018;29:44–70. doi: 10.1093/annonc/mdx738. - DOI - PubMed

[3] Van Cutsem E., Lenz H.J., Kohne C.H., Heinemann V., Tejpar S., Melezinek I., Beier F., Stroh C., Rougier P., van Krieken J.H., et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J. Clin. Oncol. 2015;33:692–700. doi: 10.1200/JCO.2014.59.4812. - DOI - PubMed

[4] Van Cutsem E., Lenz H.J., Kohne C.H., Heinemann V., Tejpar S., Melezinek I., Beier F., Stroh C., Rougier P., van Krieken J.H., et al. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J. Clin. Oncol. 2015;33:692–700. doi: 10.1200/JCO.2014.59.4812. - DOI - PubMed

[5] Douillard J.Y., Oliner K.S., Siena S., Tabernero J., Burkes R., Barugel M., Humblet Y., Bodoky G., Cunningham D., Jassem J., et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N. Engl. J. Med. 2013;369:1023–1034. doi: 10.1056/NEJMoa1305275. - DOI - PubMed

[6] Douillard J.Y., Oliner K.S., Siena S., Tabernero J., Burkes R., Barugel M., Humblet Y., Bodoky G., Cunningham D., Jassem J., et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N. Engl. J. Med. 2013;369:1023–1034. doi: 10.1056/NEJMoa1305275. - DOI - PubMed

[7] Bokemeyer C., Kohne C.H., Ciardiello F., Lenz H.J., Heinemann V., Klinkhardt U., Beier F., Duecker K., van Krieken J.H., Tejpar S. FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer. Eur. J. Cancer (Oxf. Engl. 1990) 2015;51:1243–1252. doi: 10.1016/j.ejca.2015.04.007. - DOI - PMC - PubMed

[8] Bokemeyer C., Kohne C.H., Ciardiello F., Lenz H.J., Heinemann V., Klinkhardt U., Beier F., Duecker K., van Krieken J.H., Tejpar S. FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer. Eur. J. Cancer (Oxf. Engl. 1990) 2015;51:1243–1252. doi: 10.1016/j.ejca.2015.04.007. - DOI - PMC - PubMed

[9] Sawada K., Nakamura Y., Yamanaka T., Kuboki Y., Yamaguchi D., Yuki S., Yoshino T., Komatsu Y., Sakamoto N., Okamoto W., et al. Prognostic and Predictive Value of HER2 Amplification in Patients With Metastatic Colorectal Cancer. Clin. Colorectal Cancer. 2018;17:198–205. doi: 10.1016/j.clcc.2018.05.006. - DOI - PubMed

[10] Sawada K., Nakamura Y., Yamanaka T., Kuboki Y., Yamaguchi D., Yuki S., Yoshino T., Komatsu Y., Sakamoto N., Okamoto W., et al. Prognostic and Predictive Value of HER2 Amplification in Patients With Metastatic Colorectal Cancer. Clin. Colorectal Cancer. 2018;17:198–205. doi: 10.1016/j.clcc.2018.05.006. - DOI - PubMed

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Circulating Tumor DNA as a Novel Biomarker Optimizing Chemotherapy for Colorectal Cancer

Affiliation

Circulating Tumor DNA as a Novel Biomarker Optimizing Chemotherapy for Colorectal Cancer

Authors

Affiliation

Abstract

Conflict of interest statement

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