Abstract 605: Evidence that a wide variety of cancers may use the progesterone induced blocking factor protein to escape immune surveillance as evidenced by significant palliation following treatment with progesterone receptor antagonists in advanced metastatic treatment resistant cancers

Abstract

Abstract A search of the literature and abstracts from national oncology meetings was conducted to determine what types of human cancers have been reported to show some type of palliative benefit from treatment with progesterone (P) receptor antagonists. Though the original concept was to try P receptor antagonists for cancers known to be associated with the classic nuclear P receptor, recent data suggest that the real beneficial target is a membrane P receptor that helps produce a unique immunomodulatory protein called the progesterone induced blocking factor (PIBF) that inhibits natural killer (NK) cells and cytotoxic T cells in the tumor microenvironment and thus may allow cancer cells to metastasize. The following human cancers known to be associated with the classic nuclear receptor that have responded to either the P receptor modulator mifepristone or onapristone, include breast, uterine, ovarian, and prostate cancer. Human cancers not associated with the classic nuclear P receptor that have demonstrated significant palliative benefits and/or increased longevity following P receptor modulator therapy include colon, thymic cell epithelial cancer, transitional cell carcinoma of the renal pelvis, leiomyosarcoma, pancreatic carcinoma, malignant fibrous histiocytoma, glioblastoma multiforme grade IV, renal cell carcinoma, fibrous osteosarcoma, small cell lung cancer, non-small cell lung cancer (including those negative for tumor markers, or those positive for PD-1, or positive for the EGFR mutation). The wide variety of very advanced cancers that have responded to the P receptor modulators as evidenced by extension of a better quality of life despite the fact that they had progressed despite standard chemo or immunotherapy, is consistent with the concept that PIBF may be a protein needed by a large variety of cancers to advance or metastasize, and thus may provide a unique target to treat with P receptor modulators, and thus provide significant palliative benefit. In contrast to most anti-cancer agents, P receptor antagonists are extremely well tolerated, and are without serious risk of complications. Larger series are needed to determine the true beneficial effect of this type of therapy. Positive beneficial effects in case reports, at least provide the basis for selection of which cancers to evaluate in a larger series. Citation Format: Jerome H. Check, Diane Check, Carrie Wilson. Evidence that a wide variety of cancers may use the progesterone induced blocking factor protein to escape immune surveillance as evidenced by significant palliation following treatment with progesterone receptor antagonists in advanced metastatic treatment resistant cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 605.