Abstract: As disclosed herein, we have discovered that creatine is a critical molecule buffering ATP levels in cancer-targeting CD8 T cells through maintaining a readily available high-energy phosphate reservoir. Building upon this discovery, we have designed a number of methods for modulating energy metabolism in a population of tumor-infiltrating CD8 T cells, methods that can be adapted for use in therapeutic regimens for the treatment of cancer. Illustrative embodiments of the invention include methods for enhancing tumor-infiltrating CD8 T cells ability to mount and sustain a response to tumor cells comprising increasing the concentrations of creatine available for tumor-infiltrating CD8 T cells energy metabolism, thereby enhancing the ability of the tumor-infiltrating CD8 T cells to mount and sustain a response to the tumor cells.

Abstract: A method for treating a hyperglycemia and hyperglycemia-dependent side effects in a subject undergoing chemotherapy includes a step of identifying a subject undergoing chemotherapy and being administered a hyperglycemia-inducing agent. Short-term starvation or a fasting mimicking diet is administered for a first time period to the subject to prevent hyperglycemia and sensitization to chemotherapy associated with increased glucose levels. The STS-mimicking drug Metformin is administrated between STS/FMD cycles to maintain STS/FMD-like conditions during the re-feeding period.

Abstract: A method of alleviating or treating symptoms of cancer and/or effects of chemotherapy or of kinase inhibitors includes a step of identifying a subject having cancer. A reduced caloric diet is administered to the subject for a first time period, the reduced caloric diet providing at most 1000 kcal per day. A kinase inhibitor is administered to the subject.

Abstract: A method for treating a hyperglycemia and hyperglycemia-dependent side effects in a subject undergoing chemotherapy includes a step of identifying a subject undergoing chemotherapy and being administered a hyperglycemia-inducing agent. Short-term starvation or a fasting mimicking diet is administered for a first time period to the subject to prevent hyperglycemia and sensitization to chemotherapy associated with increased glucose levels. The STS-mimicking drug Metformin is administrated between STS/FMD cycles to maintain STS-/FMD-like conditions during the re-feeding period.

Abstract: A method of alleviating or treating symptoms of cancer and/or effects of chemotherapy or of kinase inhibitors includes a step of identifying a subject having cancer. A reduced caloric diet is administered to the subject for a first time period, the reduced caloric diet providing at most 1000 kcal per day. A kinase inhibitor is administered to the subject.