(A-B) MCA38 WT cells were left untreated or treated with cisplatin or mitomycin C at the indicated concentrations overnight prior to ATP pulse treatment (ATP 1 mM, 15 min). Cell viability was evaluated after 24 hr. Overall response (A) and drug dose response curve at 40°C (B) were analyzed. (C) Schematic illustration showing the use of hyperthermia with ATP as a new approach to elicit maximal tumor cell death in association with traditional chemotherapy. Hyperthermia, by promoting plasma membrane fluidity, increases P2X7 sensitivity to ATP and therefore enhances ATP tumor-killing activity. The combination of hyperthermia, ATP and conventional chemotherapy would consequently elicit maximal tumor cell death while circumventing side effects of high dose of cytotoxic drugs. *p < 0.05 when compared cells treated with ATP to cells without ATP treatment (two-way ANOVA, followed by Bonferroni pos-test, mean ± SD).