Clinical utility of circulating tumor DNA for colorectal cancer

Abstract

Colorectal cancer (CRC) is currently the most common type of cancer in Japan, and its prognosis has improved because of development of diagnosis and advancement in treatments including surgery and chemotherapy. However, because of intratumor heterogeneity and clonal evolution, tumors often develop resistance to treatment. Genotyping tumor tissue in search of somatic genetic alterations for actionable information has become routine examination in clinical practice. However, the inherent molecular heterogeneity of metastatic tumors and the ability of cancer genomes to dynamically evolve are not properly captured by tissue specimens only. Circulating tumor DNA (ctDNA) carrying tumor‐specific genetic or epigenetic alterations is released into the circulation from tumor cells undergoing apoptosis or necrosis. Analysis of ctDNA has the potential to change clinical practice by exploiting blood rather than tissue, as a source of information. Here, we provide an overview of the characteristics of ctDNA and focus on detection methods for ctDNA, and the feasibility of use of ctDNA to monitor tumor dynamics for patients with colorectal cancer.

Identification of 10 Hub genes related to the progression of colorectal cancer by co-expression analysis

“…For example, effective prognostic biomarkers for CRC are CEA levels, circulating tumor DNA (ctDNA), MS instability and certain genetic characteristics (Duffy, 2015). Analysis can be used to diagnose, identify and track tumor-specific changes associated with disease progression and to guide treatment decisions (Osumi et al, 2019). miRNAs can also be used as diagnostic and prognostic biomarkers for assessing tumor development, progression, invasion, metastasis and reaction to chemotherapeutic drugs (Shirafkan et al, 2018).…”

<p>Emerging Role of Immunotherapy for Colorectal Cancer with Liver Metastasis</p>

“…149 Even in MSS CRCs, mutational/neoantigen load has demonstrated some association with immune infiltration and survival, showing promise for successful exploration of immunotherapies. 150 The median PFS in patients with advanced CRC treated with pembrolizumab combined with chemotherapy was 16.9 months, and the median OS was 18.8 months (median follow-up 7.9 months). 151 In phase Ib/II trials of RAS wild-type mCRC patients treated with pembrolizumab plus cetuximab, seven of nine patients were stable and had good tolerance.…”

Clinical Perspective and Translational Oncology of Liquid Biopsy

“…Thus, the detection of the molecular mechanisms of resistance in ctDNA can guide clinicians to avoid continuing with ineffective treatments and decide on personalized treatment after progression to anti EGFR drugs. Clinical trials of ctDNA include microsatellite instability (MSI) testing and evaluation of tumor tissue mutational burden (TMB) in ctDNA to identify patients with metastatic high microsatellite instability (MSI-H) colorectal carcinoma who can guide immunotherapy and assess response in serial extractions of ctDNA [37]. Finally, the usefulness of ctDNA for detecting MRD in patients with colorectal cancer has also been described [38] and quantification of ctDNA correlates with tumor load and allows the use of evaluate early response to cancer treatment [34].…”