Tumor resistance to therapy: a genetic or kinetic problem?

Chinese hamster V79 spheroids exposed to cisplatin for 2 hr daily for 3 weeks responded very similarly to tumors undergoing chemotherapy. Initially, the number of viable cells per spheroid decreased in a dose-dependent fashion but, after several treatments, the apparent effectiveness of the cisplatin decreased. At low doses, spheroid regrowth eventually occurred despite continued therapy. A detailed examination of the cellular basis for this response showed that the so-called acquired resistance was not due to a change in cellular responsiveness to cisplatin but, rather, was the result of a marked increase in the cellular growth fraction in the treated spheroids.