TY - JOUR
T1 - Minimal Residual Disease in Colorectal Cancer
T2 - Are We Finding the Needle in a Haystack?
AU - Jácome, Alexandre A.
AU - Johnson, Benny
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/4
Y1 - 2023/4
N2 - Despite significant advances in the surgical and systemic therapy of colorectal cancer (CRC) in recent decades, recurrence rates remain high. Apart from microsatellite instability status, the decision to offer adjuvant chemotherapy to patients with CRC is solely based on clinicopathologic factors, which offer an inaccurate risk stratification of patients who derive benefit from adjuvant therapy. Owing to the recent improvements of molecular techniques, it has been possible to detect small allelic fractions of circulating tumor DNA (ctDNA), and therefore, to identify patients with minimal residual disease (MRD) after curative-intent therapies. The incorporation of ctDNA identifying MRD in clinical practice may dramatically change the standard of care of CRC, refining the selection of patients who are candidates for escalation and de-escalation of adjuvant chemotherapy, and even for organ-preservation strategies in rectal cancer. In the present review, we describe the current standard of care and the DNA sequencing methodologies and assays, present the data from completed clinical studies and list ongoing potential landmark clinical trials whose results are eagerly awaited, as well as the impact and perspectives for the near future. The discussed data bring optimism for the future of oncologic care through the hope of refined utilization of adjuvant therapies with higher efficacy and safety for patients with both localized and advanced CRC.
AB - Despite significant advances in the surgical and systemic therapy of colorectal cancer (CRC) in recent decades, recurrence rates remain high. Apart from microsatellite instability status, the decision to offer adjuvant chemotherapy to patients with CRC is solely based on clinicopathologic factors, which offer an inaccurate risk stratification of patients who derive benefit from adjuvant therapy. Owing to the recent improvements of molecular techniques, it has been possible to detect small allelic fractions of circulating tumor DNA (ctDNA), and therefore, to identify patients with minimal residual disease (MRD) after curative-intent therapies. The incorporation of ctDNA identifying MRD in clinical practice may dramatically change the standard of care of CRC, refining the selection of patients who are candidates for escalation and de-escalation of adjuvant chemotherapy, and even for organ-preservation strategies in rectal cancer. In the present review, we describe the current standard of care and the DNA sequencing methodologies and assays, present the data from completed clinical studies and list ongoing potential landmark clinical trials whose results are eagerly awaited, as well as the impact and perspectives for the near future. The discussed data bring optimism for the future of oncologic care through the hope of refined utilization of adjuvant therapies with higher efficacy and safety for patients with both localized and advanced CRC.
KW - adjuvant
KW - chemotherapy
KW - circulating tumor DNA
KW - colorectal neoplasms
KW - high-throughput nucleotide sequencing
KW - neoplasm
KW - residual
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U2 - 10.3390/cells12071068
DO - 10.3390/cells12071068
M3 - Review article
C2 - 37048141
AN - SCOPUS:85152314157
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 7
M1 - 1068
ER -