Targeting the Roots of Cancer Through a Deeper Understanding of Cancer Stem Cells

Cancer is a complex system and can be viewed through many lenses. The “Hallmarks of Cancer” published by Hanahan and Weinberg in 2000 and 2011 provides the original and updated conceptual framework of cancer cell biology. More recently, in 2022, Hanahan further published “Hallmarks of Cancer: New Dimensions” (Cancer Discov 2022) which highlighted additional emerging hallmarks and enabling characteristics, including those under the umbrella of ‘unlocking phenotypic plasticity’. Relative to the huge amount of development and differentiation that occurs during organogenesis (embryonic differentiation), cells are typically restricted in the extent to which they can differentiate. This restriction allows cells to remain organized and functional within their respective tissue. In cancer, however, cells undergo molecular and phenotypic changes that allow them to adopt different identities along a phenotypic spectrum referred to as cellular plasticity. Phenotypic plasticity thus describes the ability of cancer cells to undergo dynamic, non-genetic cell state changes that amplify cancer heterogeneity to promote therapy evasion. Human tumors are known to contain less differentiated cells that are resistant to therapy and associated with the development of relapse and metastasis. We are interested in a better understanding of how a more undifferentiated and stemness state in cancer can contribute to therapy resistance and tumor recurrence. Tumor types particularly prevalent in Southeast Asia and Hong Kong, including hepatocellular carcinoma and gastric cancer, are currently used as model systems in our studies. Efforts are directed at conducting basic and pre-clinical studies using a combination of molecular, cellular, OMICs, and disease modeling approaches, with an ultimate goal to translate the findings in the lab into better patient care in the clinic.