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Cancer

Methotrexate for gestational choriocarcinoma: a paradigm shift in oncology

Nature Reviews Endocrinology volume 19, page 501 (2023)Cite this article

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Prior to the 1950s, cancer therapy largely comprised two pillars: surgery and radiation. There was a clear need to develop medicines to treat the disease and/or its symptoms, but the lack of mechanistic insights into cancer biology constrained drug discovery efforts. Furthermore, at that time, micrometastasis was largely overlooked, and the therapeutic utility of tumour markers was also not readily apparent.

Folate is an essential vitamin (B9): through its conversion by dihydrofolate reductase (DHFR) to dihydrofolate and then to tetrahydrofolate, a coenzyme in the synthesis of nucleic acids, it is indispensable for DNA synthesis and repair. Antifolates constitute a class of currently used chemotherapeutics that work by antagonizing these actions of folate. Insights into the clinical importance of folate emerged in the 1940s. Beginning in 1948, Sidney Farber and colleagues demonstrated that the antifolates aminopterin and amethopterin (now known as methotrexate), which competitively inhibit DHFR, induced temporary remissions of acute lymphoblastic leukaemia in children. Working at the National Cancer Institute (NCI) in Bethesda, Maryland, USA, from the mid-1940s, Roy Hertz showed in animal models that antifolates inhibited the oestrogen-driven growth of tissues in the female reproductive tract. And, treating patients with cancer at Memorial Sloan Kettering in New York in the early 1950s, Min Chiu Li observed reductions in levels of human chorionic gonadotropin (hCG) from routine urinalyses of a patient treated with methotrexate.

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References

Original article

  • Li, M. C., Hertz, R. & Spencer, D. B. Effect of methotrexate therapy upon choriocarcinoma and chorioadenoma. Proc. Soc. Exp. Biol. Med. 93, 361–366 (1956)

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Related articles

  • Li, M. C., Hertz, R. & Bergenstal, D. M. Therapy of choriocarcinoma and related trophoblastic tumors with folic acid and purine antagonists. N. Engl. J. Med. 259, 66–74 (1958)

    Article  CAS  PubMed  Google Scholar 

  • Hertz, R., Bergenstal, D. M., Lipsett, M. B., Price, E. B. & Hilbish, T. F. Chemotherapy of choriocarcinoma and related trophoblastic tumors in women. J. Am. Med. Assoc. 168, 845–854 (1958)

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY, USA

    Alfred C. Chin

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  1. Alfred C. Chin
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Correspondence to Alfred C. Chin.

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The author declares no competing interests.

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Chin, A.C. Methotrexate for gestational choriocarcinoma: a paradigm shift in oncology. Nat Rev Endocrinol 19, 501 (2023). https://doi.org/10.1038/s41574-023-00874-9

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