Establishing patient-tailored variability-based paradigms for anti-cancer therapy: Using the inherent trajectories which underlie cancer for overcoming drug resistance.

Drug resistance is a major obstacle for successful therapy of many malignancies and is affecting the loss of response to chemotherapy and immunotherapy. Tumor-related compensatory adaptation mechanisms contribute to the development of drug resistance. Variability is inherent to biological systems and altered patterns of variability are associated with disease conditions. The marked intra and inter patient tumor heterogeneity, and the diverse mechanism contributing to drug resistance in different subjects, which may change over time even in the same patient, necessitate the development of personalized dynamic approaches for overcoming drug resistance. Altered dosing regimens, the potential role of chronotherapy, and drug holidays are effective in cancer therapy and immunotherapy. In the present review we describe the difficulty of overcoming drug resistance in a dynamic system and present the use of the inherent trajectories which underlie cancer development for building therapeutic regimens which can overcome resistance. The establishment of a platform wherein patient-tailored variability signatures are used for overcoming resistance for ensuing long term sustainable improved responses is presented.