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First Strike-Second Strike Strategies in Metastatic Cancer: Lessons from the Evolutionary Dynamics of Extinction

Robert A Gatenby1,2,3, Jingsong Zhang4, Joel S Brown5,3

  • 1Cancer Biology and Evolution Program, Moffitt Cancer Center, Tampa, Florida. robert.gatenby@moffitt.org.

Cancer Research
|June 22, 2019
PubMed

Insights

Sequencing noncurative cancer therapies can achieve cures by reducing tumor heterogeneity and size. This eco-evolutionary strategy, akin to background extinctions, clears cancer populations for potential eradication.

Area of Science:

  • Oncology
  • Evolutionary Biology
  • Mathematical Biology

Background:

  • Cancer's diversity and evolution present significant challenges to achieving cures.
  • Current cancer therapies, while effective, often fail to eradicate the disease due to tumor adaptability.

Purpose of the Study:

  • To propose a novel therapeutic strategy for achieving curative outcomes in cancer.
  • To explore the application of eco-evolutionary principles to cancer treatment sequencing.

Main Methods:

  • Deriving principles from eco-evolutionary dynamics, specifically background extinction models.
  • Modeling a "first strike" to reduce tumor size and heterogeneity, followed by "second strikes" to induce extinction.

Main Results:

  • A "first strike" followed by immediate "second strikes" can reduce cancer populations below a critical threshold.
  • This sequenced approach can lead to the inevitable extinction of cancer populations.

Conclusions:

  • Curative cancer outcomes may be achievable through carefully sequenced, individually noncurative therapies.
  • The proposed strategy shows parallels with successful treatments like that for childhood acute lymphocytic leukemia.

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