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Chemotherapy-induced Reversion of Mutant to Wild-type in Metastatic Colorectal Cancer. | LitMetric

AI Article Synopsis

  • A new study investigated how liquid biopsy can track mutations in the RAS gene in colorectal cancer patients during chemotherapy, revealing that some patients can become NeoRAS-wt (wild type) despite initially having a RAS mutation.
  • In a group of 129 patients, conversion to NeoRAS-wt was seen in 43.5% of RAS-mt patients, leading to better treatment responses and significantly improved outcomes after six months.
  • The findings suggest that monitoring for NeoRAS-wt through liquid biopsy could inform treatment strategies, particularly the use of anti-EGFR monoclonal antibody therapies for metastatic colorectal cancer.

Article Abstract

Background/aim: Secondary mutation of mutated RAS, induced by chemotherapy, is thought to be rare. However, introduction of liquid biopsy (LB) has made it possible to monitor RAS status in patients' plasma throughout the course of chemotherapy for metastatic colorectal cancer (mCRC), and disappearance of the RAS mutation (RAS-mt), i.e., the NeoRAS-wt phenomenon, has been reported and is receiving attention, especially with respect to treatment implications.

Patients And Methods: A prospective study of 129 patients undergoing chemotherapy for mCRC (RAS-wt, n=65; RAS-mt, n=64) was carried out. Plasma RAS status was monitored in these patients by LB. Relations between secondary genetic change, chemotherapy, and 6-month disease outcomes were analyzed. The effect of anti-EGFR mAb therapy on NeoRAS-wt mCRC was also examined.

Results: NeoRAS-wt was detected in 27 (43.5%) RAS-mt patients overall and in all patients with a G12S or Q61H mutation. First-line treatment was more effective among NeoRAS-wt patients than non-NeoRAS-wt patients (70.9% vs. 48.6% overall response rate, p=0.087), and the time from treatment to LB was shorter in this group. Six-month outcomes were significantly better in the NeoRAS-wt group (p<0.001), and conversion to NeoRAS-wt was found to be predictive of a good outcome (OR=7.886, 95% CI=2.458-25.30; p<0.001). Anti-EGFR mAb therapy was found to restrict disease progression in NeoRAS-wt patients.

Conclusion: Conversion to NeoRAS-wt is relatively frequent, and it may predict good responses to treatment. Anti-EGFR mAb therapy was effective for our NeoRAS-wt patients. Detection of NeoRAS-wt by LB may significantly change the indication for anti-EGFR mAb therapy and the mCRC treatment strategy.

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Source
http://dx.doi.org/10.21873/anticanres.15740DOI Listing

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