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Studies on Cross-Resistance and Collateral Sensitivity (1962–1964)¹

Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, and Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University Medical College, New York, New York

The literature on resistance to cancer chemotherapeutic drugs in experimental biologic systems during a 2-year period beginning in early 1962 is presented in detail. Emphasis has been placed on those experimental systems in which alterations due to a shift to resistance to 1 drug have resulted in either cross-resistance or collateral sensitivity to other anti-cancer drugs.

The importance of the problem of drug resistance in cancer chemotherapy is emphasized by the many new systems and new drugs discussed. There have been intensive investigations with amethopterin (methotrexate) and several new agents such as MGGH [methylglyoxal-bis(guanylhydrazone)], the Vinca alkaloids, and the phthalanilide derivatives. During the past 2 years 107 biologic systems resistant to potential anti-cancer drugs have been described, and more than half were resistant to amethopterin. This number is to be added to the 352 resistant systems described previously.

Resistance to a given drug is not always the result of a common alteration. Multiple mechanisms of resistance are exemplified by the summation of the available data. There is increasing evidence for the genetic control of a specific resistance level in certain biologic systems, which in turn controls the patterns of cross-resistance and collateral sensitivity.

¹ This work was supported in part by Grant CA-03192-07 from the National Cancer Institute, NIH, Bethesda, Maryland, and by Grant T-107 from the American Cancer Society.