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Precision Oncology: Between Vaguely Right and Precisely Wrong.

Amy Brock1, Sui Huang2

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Precision Oncology faces challenges due to tumor heterogeneity and non-genetic factors. Understanding these complexities is key to improving cancer treatment effectiveness.

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Area of Science:

  • Oncology
  • Genomics
  • Cancer Biology

Background:

  • Precision Oncology aims to target tumor-driving mutations.
  • Growing concerns question the effectiveness of current Precision Oncology approaches.
  • Tumor heterogeneity and non-genetic factors complicate targeted therapies.

Purpose of the Study:

  • To explore the biological basis for the "imprecision" in Precision Oncology.
  • To review evidence challenging the traditional driver mutation hypothesis.
  • To discuss the implications of tumor cell plasticity and non-genetic dynamics for cancer treatment.

Main Methods:

  • Review of current literature on Precision Oncology.
  • Analysis of findings related to tumor heterogeneity and genomic sequencing.
  • Examination of studies on oncogenic mutations, cell phenotype switching, and treatment resistance.

Main Results:

  • Precision Oncology's reliance on biopsy sequencing may not capture tumor heterogeneity.
  • Accumulating evidence suggests mutations may not always be the primary drivers of cancer progression.
  • Cancer cells surviving treatment can adopt stem cell-like states, promoting recurrence.

Conclusions:

  • There is no simple linear relationship between a tumor's genotype and its phenotype.
  • Non-genetic factors and imprecise phenotype dynamics significantly impact tumor behavior.
  • Embracing these complex dynamics is crucial for advancing Precision Oncology and achieving clinical benefits.