Progesterone receptor modulators provide significant palliation for a variety of advanced cancers including tumors devoid of the classic nuclear progesterone receptor
Jerome H Check
Cooper Medical School of Rowan University, USA
: J Clin Exp Oncol
Abstract
The progesterone receptor modulator mifepristone has been found to prolong length and quality of life in mice and humans with advanced cancers of various types. Most of these cancers are not known to be associated with the classic nuclear progesterone (P) receptor. Some of these tumors in controlled animal studies include leukemia, lung and testicular cancer, and prostate cancer (the latter associated with nuclear P receptor in humans, not sure in mice). Human cancers that benefited from mifepristone therapy without evidence of presence of classic nuclear receptor includes colon, pancreatic, renal cell, transitional cell carcinoma of the renal pelvis, thymic epithelial cell, malignant fibrous histiocytoma, and small and nonsmall cell lung cancer. Anecdotal benefits have been found also in those with the presence of the classic nuclear P receptor, e.g., breast and ovarian cancer and leiomyosarcoma, but the benefits may be from non-epigenetic effects on membrane P receptors. The mechanism is believed to be by inhibiting the conversion of a 90 kDa 757 amino acid “parent” protein, known as the progesterone induced blocking factor (PIBF), to intracytoplasmic splice variants which act to suppress natural killer cell activity by stabilizing perforin granules. PIBF also causes a shift from TH1 cytotoxic T-cells to antibody secreting TH2 cytokine dominant T-cells. Some of the anecdotal cases have improved quality and length of life despite the severity of the cancer leaving little question of its efficacy in these cases, especially since the mifepristone was used as single agent therapy.
Biography
Jerome H Check is a Professor of Obstetrics and Gynecology and Division Head of Reproductive Endocrinology at Cooper Medical School of Rowan University, New Jersey, USA. He is also board certified in Internal Medicine and Medical Endocrinology. He is a lead author (predominantly) or co-author of over 750 peer-reviewed manuscripts. His first publication in a Cancer Journal was in 1971 and he has several recent publications involving his research into Cancer Immunology, especially as it relates to similarities of the fetal placental unit and cancer in avoiding immune surveillance.
