Comprehending phenotypic plasticity in cancer and evolution

Kulkarni, Prakash; Salgia, Ravi

doi:10.1016/j.isci.2024.109308

Cited by 1 publication

(1 citation statement)

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“…Additionally, computational models investigating stochastic phenotypic switching in bacteria [ 13 ] showed that when a genetic mutation renders the population less fit, switching to an alternative phenotype with higher fitness gives the population sufficient time to develop compensatory mutations, demonstrating that phenotypic switching can reduce the time to adaptation by orders of magnitude. Together, these observations lend further credence to the idea that phenotypic plasticity is of fundamental importance in developing drug resistance and speeding up the evolution of bacteria and cancer cells [ 14 ] ( Figure 1 ). Furthermore, group behavior emerging from phenotypic plasticity can sustain a heterogeneous cancer cell population with multiple interchangeable phenotypes, producing temporary drug tolerance and facilitating the initiation and progression to permanent drug resistance [ 4 , 7 , 10 , 11 , 15 ].…”

Section: Introductionsupporting

confidence: 66%

Leveraging Cancer Phenotypic Plasticity for Novel Treatment Strategies

Ramisetty,

Subbalakshmi,

Pareek

et al. 2024

JCM

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Cancer cells, like all other organisms, are adept at switching their phenotype to adjust to the changes in their environment. Thus, phenotypic plasticity is a quantitative trait that confers a fitness advantage to the cancer cell by altering its phenotype to suit environmental circumstances. Until recently, new traits, especially in cancer, were thought to arise due to genetic factors; however, it is now amply evident that such traits could also emerge non-genetically due to phenotypic plasticity. Furthermore, phenotypic plasticity of cancer cells contributes to phenotypic heterogeneity in the population, which is a major impediment in treating the disease. Finally, plasticity also impacts the group behavior of cancer cells, since competition and cooperation among multiple clonal groups within the population and the interactions they have with the tumor microenvironment also contribute to the evolution of drug resistance. Thus, understanding the mechanisms that cancer cells exploit to tailor their phenotypes at a systems level can aid the development of novel cancer therapeutics and treatment strategies. Here, we present our perspective on a team medicine-based approach to gain a deeper understanding of the phenomenon to develop new therapeutic strategies.

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