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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Related Experiment Video

Updated: Jul 27, 2025

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
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Irinotecan- vs. Oxaliplatin-Based Doublets in KRAS

Vincenzo Formica1, Cristina Morelli1, Veronica Conca2

  • 1Medical Oncology Unit, Department of Medicine of the Systems, University of Rome Tor Vergata, 00133 Rome, Italy.

Cancers
|June 10, 2023
PubMed
Summary

First-line irinotecan chemotherapy offers superior survival outcomes for patients with KRASG12C-mutated metastatic colorectal cancer compared to oxaliplatin-based regimens. This finding is crucial for optimizing treatment strategies.

Keywords:
KRASG12C mutationirinotecanmetastatic colorectal canceroxaliplatin

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Area of Science:

  • Oncology
  • Medical Genetics
  • Clinical Pharmacology

Background:

  • KRASG12C-mutated metastatic colorectal cancer (mCRC) is a distinct molecular subtype with limited chemotherapy sensitivity data.
  • The optimal chemotherapy backbone for combination therapy with KRASG12C inhibitors is currently unknown.
  • Understanding chemotherapy response in this specific mCRC population is critical for future treatment advancements.

Purpose of the Study:

  • To compare the efficacy of first-line FOLFIRI versus FOLFOX chemotherapy in patients with KRASG12C-mutated mCRC.
  • To identify the preferred chemotherapy regimen for KRASG12C-mutated mCRC.
  • To inform the selection of chemotherapy backbones for combination therapies involving KRASG12C inhibitors.

Main Methods:

  • A multicentre retrospective analysis of KRASG12C-mutated mCRC patients treated with first-line FOLFIRI or FOLFOX +/- bevacizumab.
  • Propensity-score-matched analysis (PSMA) was employed to control for key patient and disease characteristics.
  • Subgroup analyses were conducted to explore treatment-effect interactions.

Main Results:

  • In the propensity-score-matched cohort, irinotecan-based regimens demonstrated significantly improved progression-free survival (PFS) and overall survival (OS) compared to oxaliplatin-based regimens.
  • 12-month PFS rates were 55% with irinotecan vs. 31% with oxaliplatin (HR 0.40, p=0.01).
  • Median OS was 37.9 months with irinotecan vs. 21.7 months with oxaliplatin (HR 0.45, p=0.045).

Conclusions:

  • First-line irinotecan-based chemotherapy significantly enhances survival outcomes in KRASG12C-mutated mCRC patients.
  • Irinotecan-based regimens should be preferred over oxaliplatin in this patient population.
  • These results have implications for selecting chemotherapy backbones in future targeted therapy combinations.