How cancer cell plasticity shapes adaptive therapy outcomes

– Kedhar R Thyagarajan

Cancer cells often gain resistance to new therapies, hindering successful outcomes. To combat this, scientists are turning to adaptive therapy, a strategy in which drug doses are adjusted to allow a small population of drug-sensitive cancer cells to survive. These remaining cells compete with drug-resistant cancer cells and limit their growth.

However, cancer cells can sometimes switch between drug-resistant and drug-sensitive states. This plasticity can compromise the effectiveness of adaptive therapy, as even drug-sensitive cells may escape treatment by temporarily becoming resistant. In a new study published in Mathematical Biosciences, researchers from the Department of Bioengineering, IISc, along with collaborators from the USA, shed light on how such plasticity can influence adaptive therapy outcomes.

The researchers developed a mathematical model to investigate the effect of cancer cell plasticity and competition between drug-sensitive and drug-resistant cells on treatment efficacy. They studied the cells’ behaviours in response to two types of cancer drugs: cytotoxic drugs, which kill cancer cells, and cytostatic drugs, which stop them from dividing.

Their results suggest that the plasticity of cancer cells worsened outcomes in cytotoxic drugs, but surprisingly, it was associated with a better outcome in the case of cytostatic drugs. In the latter case, continuous dosing, rather than adaptive therapy, was found to be more effective, especially when cells are stopped from switching states.

When the team tested an equal mix of drug-resistant and drug-sensitive cancer cells, they found that constant dosing was worse than adaptive therapy, but in general both types of therapy had worse outcomes if the cancer cells were left to grow before treatment. The team also found that adaptive therapy worked better on tumours that were diagnosed in late stages.

With rising cancer rates globally, these findings underscore the need for better therapy design and deeper understanding of tumour processes.

REFERENCE:

Vibishan B, Jain P, Sharma V, Hari K, Kadelka C, George JT, Jolly MK, Impacts of competition and phenotypic plasticity on the viability of adaptive therapy, Mathematical Biosciences (2025)

https://www.sciencedirect.com/science/article/abs/pii/S0025556425001488?via%3Dihub

LAB WEBSITE:

https://be.iisc.ac.in/~mkjolly/