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Clinical trial designs for evaluating and exploiting cancer evolution.

Alvaro H Ingles Garces1, Nuria Porta2, Trevor A Graham3

  • 1Drug Development Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, UK.

Cancer Treatment Reviews
|June 18, 2023
PubMed
Summary

Understanding cancer

Keywords:
Cancer evolutionClinical trialsDrug resistance

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Area of Science:

  • Oncology
  • Cancer Biology
  • Evolutionary Medicine

Background:

  • Drug resistance in cancer leads to treatment failure.
  • Clonal evolution and collateral sensitivity can be modeled.
  • Cell-cell competition influences tumor population dynamics.

Purpose of the Study:

  • To explore novel therapeutic strategies for cancer treatment.
  • To propose new clinical trial designs for steering cancer evolution.
  • To leverage understanding of clonal dynamics for improved patient outcomes.

Main Methods:

  • Modeling clonal evolution and collateral sensitivity.
  • Investigating cell-cell competition for nutrients/blood supply.
  • Utilizing next-generation sequencing for longitudinal clonal dynamics assessment.

Main Results:

  • Preclinical evidence supports modeling herding of clonal evolution.
  • Initial treatments can favorably influence subsequent responses.
  • Exploiting cell-cell competition suggests intermittent dosing or treatment cycling.

Conclusions:

  • Cancer evolution can be therapeutically exploited.
  • New clinical trial designs are needed to incorporate evolutionary principles.
  • Longitudinal assessment of clonal dynamics will enhance response/resistance evaluation.