Application of Evolutionary Principles to Cancer Therapy

Abstract

The dynamic cancer ecosystem, with its rich temporal and spatial diversity in environmental conditions and heritable cell phenotypes, is remarkably robust to therapeutic perturbations. Even when response to therapy is clinically complete, adaptive tumor strategies almost inevitably emerge and the tumor returns. Although evolution of resistance remains the proximate cause of death in most cancer patients, a recent analysis (1) found that evolutionary terms were included in less than 1% of manuscripts on the cancer treatment outcomes and this has not changed in 30 years. Here we review treatment methods that attempt to understand and exploit intratumoral evolution to prolong response to therapy. In general, we find that treating metastatic (i.e. non-curable) cancers using the traditional strategy aimed at killing the maximum number of tumor cells is evolutionarily unsound because, by eliminating all treatment-sensitive cells, it enables rapid proliferation of resistant populations – a well-known evolutionary phenomenon termed “competitive release (2, 3).” Alternative strategies such as adaptive therapy (4, 5), “ersatzdroges (6),” and double bind treatments (7) shift focus from eliminating tumor cells to evolution-based methods that suppress growth of resistant populations to maintain long term control.

Brain metastasis: Unique challenges and open opportunities

“…While this represents a competitive advantage for brain metastases, over-reliance on these functions can serve as a therapeutic Achilles’ heel. This concept, borrowed from ecology, can be thought of as an evolutionary double bind [120, 121]; cancer cells that have become adept at certain specific functions also make themselves vulnerable to complementary therapeutic targeting. By using the right models and asking the right questions, it will be possible to identify the pathways regulating such functional advantages and turn them into a new wave of brain metastasis-specific therapeutic targets.…”

Inhibition of cancer cell migration with CuS@mSiO₂-PEG nanoparticles by repressing MMP-2/MMP-9 expression

“…However, destroying cancer cells topically never fulfills the aim of cancer therapy. 13 The unlimited proliferation and metastasis, rather than the tumor at the primary site, lead to the high mortality of cancers. Precision medicine is often in conflict with extended radical resection.…”

Group Selection May Explain Cancer Predisposition and Other Human Traits’ Evolution

“…This concept could redefine our therapeutic strategies. We must not forget that the evolutionary theory of micro-environment of cancer cells ultimately determined the strategy of anti-cancer combinational therapies (Gillies et al 2012;Enriquez-Navas et al 2015). Group selection is an idea that needs revisiting and experimental examination.…”