Tumor cell plasticity: the challenge to catch a moving target

Every cancer cell is “different”—within one and the same tumor, between different lesions originating from the same tumor, among different patients suffering from the same tumor type, and certainly between different tumor types. The complexity of tumor development, with its genetic, phenotypic and functional heterogeneity and plasticity within tumors and between primary tumors and metastases, underlies the unpredictable influences and stimuli of a tumor-associated inflammatory microenvironment, immune response, mechanical and metabolic stress, therapy-induced inflammation or interaction with microbiota. The stochastic and context dependent nature of these factors accounts for the difficulties to investigate the impact of resulting cell plasticity on tumor development, and justifies the challenge to prevent tumor recurrence. The emerging concept of cell plasticity and reciprocity (to change the phenotype by processing signals from the environment) throws more light on the actual complexity of tumor heterogeneity than can be expected solely from a unidirectional, classical cancer stem cell (CSC) model. To date, it remains widely unclear to what extent cell plasticity impacts tumor development, and it is difficult to assess by current methods. As a high tumor plasticity is likely to predict a poor outcome for patients, the future therapeutic challenge will be the development of personalized treatment strategies to predict and finally prevent cell plasticity in patients.