Non-Genetic Adaptive Drug Resistance in Cancer

Along with undergoing genetic evolution, tumor cells can alter their epigenetic state, intracellular signaling network, or extrinsic cell-to-cell symbiosis to adapt and resist anti-cancer treatments. This non-genetic evolution is emerging as a quintessential component of cancer resistance. In addition, the genetic landscapes of cancer cells and their non-genetic adaptive mechanisms, used to evade anti-cancer therapies, are usually linked. It has been revealed by ‘omics’ studies that some oncogenic mutations promote tumor cells to rapidly adapt to the therapeutic pressure, while other oncogenic drivers fetch an inherent cell plasticity to tumor cells enabling phenotypic switching and/or escape from immunosurveillance. Therefore, the regularity and diverse array of non-genetic resistance mechanisms raise a novel challenge to the anti-cancer therapy domain that requires innovative strategies to follow and counteract those adaptive drug resistance processes.
The first evidence for pervasive non-genetic resistance in cancer involved tumor cells entering a persistent cancer cell state. Recent progresses in charting the underlying molecular mechanisms and dynamics of cancer cell non-genetic resistance have shown multi-level regulations. However, a comprehensive view of the non-genetic drug resistance in association with immunosurveillance restrictions, genetic instability, cell invasiveness and symbiotic communications remains incomplete.

This Research Topic will focus on both the molecular and cellular processes underlying the multi-dimensional nature of cancer cell non-genetic resistance. We welcome researchers to contribute their latest original research articles as well as review articles and/or perspectives on the understanding the non-genetic resistance landscape upon different treatment regimens, including chemotherapy, radiotherapy, targeted therapy and immunotherapy.

Potential topics include but are not limited to:
• Latest technologies to investigate non-genetic evolution in vitro and in silico;
• In vivo model construction and application in adaptive resistance study;
• Transcriptional and post-transcriptional regulatory mechanisms involved in non-genetic adaptive resistance;
• Biophysical regulations involved in non-genetic drug resistance in cancer, such as liquid-liquid separation, mechanical pressure, spatial organization, etc.;
• Microenvironmental impacts on the non-genetic drug resistance;
• Clinical aspects from the point-of-view of non-genetic resistance, such as disease progression and patient survival.



Xiaoxiao Sun is one of the inventors of a patent application submitted by UCSF based on non-genetic drug resistance results.