{"entity":{"id":"paper-huggins-hodges-castration-serum-phosphatases-prostate-1941","kind":"paper","name":"Huggins and Hodges 1941: the effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate","aka":["Studies on prostatic cancer. I.","Huggins and Hodges 1941","Huggins 1941 castration prostate cancer"],"tldr":"In 1941 two Chicago surgeons showed that removing a man's testicles, or giving him oestrogen, made advanced prostate cancer shrink and his blood chemistry improve, and that giving testosterone made it worse. It was the first time any cancer in any organ had been made to regress by a drug or a hormone.","summary":"Charles Huggins and Clarence Hodges published the first of the Studies on Prostatic Cancer in Cancer Research in 1941. They measured serum acid and alkaline phosphatase in men with metastatic carcinoma of the prostate, then castrated them or gave them oestrogen, and watched the phosphatases fall and the men improve; injecting androgen sent the disease the other way.\n\nThe experiment did two things at once. It established that a human cancer can depend on a circulating hormone for its growth, which is the founding observation of systemic cancer therapy, and it gave that cancer a blood measurement that tracked it, which is the founding observation of the tumour marker. Everything on this page that suppresses, blocks or manipulates androgen descends from it, and so does the whole idea that a cancer has a dependency you can withdraw. Huggins shared the 1966 Nobel Prize in Physiology or Medicine for the work.\n\nEurope PMC indexes no abstract for the 1941 article, so OnCo carries no figures from it. The article was reprinted as a landmark in CA: A Cancer Journal for Clinicians in 1972, which is the copy Europe PMC holds (PMID 4625049, DOI 10.3322/canjclin.22.4.232).","asOf":"2026-09-25","links":[{"label":"CA Cancer J Clin 1972 reprint of the 1941 article","url":"https://doi.org/10.3322/canjclin.22.4.232"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/4625049/"},{"label":"Nobel Prize in Physiology or Medicine 1966: Charles B. Huggins","url":"https://www.nobelprize.org/prizes/medicine/1966/huggins/facts/"},{"label":"Cancer Research commentary on Huggins and Hodges (Nelson, 2016)","url":"https://europepmc.org/article/MED/26773095"}],"tags":["prostate-evidence"],"related":["hormonal-therapy-roadmap","prostate-roadmap","paper-visakorpi-androgen-receptor-amplification-nat-genet-1995"],"cancers":["prostate","prostate-mhspc","prostate-mcrpc"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adt","castration-resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-undruggable-targets"],"keyPapers":[],"journals":["cancer-research"],"dependsOn":[],"notes":[],"journal":"Cancer Research","year":1941,"authors":"Huggins C, Hodges CV.","paperType":"translational","findings":["No abstract is indexed on Europe PMC; the design (serum acid and alkaline phosphatase measured in men with metastatic carcinoma of the prostate before and after castration, oestrogen and androgen injection) is read from the article itself and from the 1972 reprint."],"whatItMeans":"The origin of hormone therapy for cancer, and the reason prostate cancer is treated by taking something away rather than adding a cytotoxic drug. More than eighty years later, every man who starts androgen deprivation is having this experiment repeated on him, and the disease is still defined by whether it has stopped responding to it.","caveats":["A small uncontrolled surgical series from 1941, reported before randomised trials existed; the size of the benefit and its duration were established later.","Serum phosphatase was the marker of the day and is not the marker now; the modern equivalent, prostate-specific antigen, was not described until 1987 (paper-stamey-psa-serum-marker-nejm-1987).","High-dose oestrogen, the other arm of the original observation, was abandoned for cardiovascular harm rather than for lack of anticancer effect; that harm is the reason luteinising hormone-releasing hormone agonists replaced it."],"changedPractice":true},"route":"/key-papers/paper-huggins-hodges-castration-serum-phosphatases-prostate-1941/","neighbours":{"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"},{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"}],"paper":[{"id":"paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","kind":"paper","name":"In vivo amplification of the androgen receptor gene and progression of human prostate cancer","route":"/key-papers/paper-visakorpi-androgen-receptor-amplification-nat-genet-1995/"},{"id":"paper-langley-lancet","kind":"paper","name":"Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme","route":"/key-papers/paper-langley-lancet/"}],"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"hormonal","kind":"section","name":"Hormonal Therapy","route":"/fronts/hormonal/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"}],"term":[{"id":"adt","kind":"term","name":"Androgen deprivation therapy (ADT)","route":"/terms/adt/"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"journal":[{"id":"cancer-research","kind":"journal","name":"Cancer Research","route":"/journals/cancer-research/"}]}}