Articles That Use the Tag Name:

progesterone receptor

Rationale for Targeting the Ras/MAPK Pathway in Triple-Negative Breast Cancer

Abstract: "Triple negative" breast cancer (TNBC) is the most aggressive and least common clinical subtype of breast cancer. As its nomenclature implies, TNBC lacks specific biomarker expression marking response to an effective targeted therapy. The incidence of TNBC is higher in young minority women who suffer from high rates of early recurrence and death from their disease. Mounting preclinical evidence supports targeting the Ras/MAPK cell signaling pathway in the TNBC subtype, despite large genomic surveys such as The Cancer Genome Atlas demonstrating infrequent canonical mutations in this pathway. Due to the early spread of TNBC, targeted treatment in the neoadjuvant setting may offer the effective therapeutic punch needed to eliminate micro-metastatic disease and reduce mortality. Herein, we will review the evidence supporting clinical trials of targeted inhibitors of the Ras/MAPK pathway in TNBC, and discuss the obstacles and opportunities of this approach. ... Read more

Catch It Before It Kills: Progesterone, Obesity, and the Prevention of Endometrial Cancer

Abstract: The lifetime risk for developing endometrial cancer, the fourth most common malignancy in women, is approximately 3%. Endometrial cancer is a hormone-driven cancer, with approximately 80% of endometrial cancers arising attributable to either an excess of estrogen or a lack of progesterone. In the normal endometrium, the proliferative effects of estrogen are normally countered by progesterone, but the absence of progesterone allows estrogen to induce oncogenesis, an effect that is amplified in situations of excess estrogen. One of the major emerging causes of the estrogen/progesterone imbalance is obesity. Obesity is associated with several hormonal derangements as well as dysregulation of insulin/insulin-like growth factor activity, which collectively contribute to hyperplasia and carcinogenesis in the endometrium. In this article, we provide an in-depth description of how obesity mechanistically promotes this hormone and growth factor imbalance. Given that endometrial cancer is clearly associated with obesity, we put forth the hypothesis that a large portion of these cancers might be prevented by treatment with progesterone. ... Read more

BRCA1 and BRCA2 Mutations and Breast Cancer

Abstract: Genetic testing for BRCA mutations is expanding in clinical oncology centers worldwide. Testing may help target unaffected high-risk women for prevention and/or close surveillance and may also help affected women choose the best chemotherapy. Annual screening with MRI appears to be an effective surveillance strategy and should be added to mammographic screening. It is important to have an understanding of the pathologic features and the natural history of BRCA-associated breast cancers in order that individualized treatments can be developed and delivered. The goals of treatment for a woman with a BRCA-associated breast cancer should be to prevent recurrence of the initial cancer and to prevent second primary breast and ovarian cancers. Women with breast cancer and a BRCA1 mutation may benefit from tailored treatments, such as with cis-platinum or olaparib. Mutations in BRCA1 are distributed in populations throughout the world and it is important that the benefits of genetic testing and of targeted therapies be made available to women who live outside of North America and western Europe. ... Read more

Endometrial Cancer: Reviving Progesterone Therapy in the Molecular Age

Abstract: Endometrial cancer is the most common gynecologic malignancy and represents a major health concern because overall five-year survival rates have not improved in the last three decades. A great deal of research demonstrates that the endometrium is extremely sensitive to hormones, and a shift in the estrogen:progesterone balance is the major cause for the development of endometrial cancer. Progestin-based therapy has proven effective in a subset of patients, particularly in situations where expression of progesterone receptor (PR) is maintained. However, this approach is not routinely used in the clinic in the U.S. for several reasons. For example, many endometrial tumors have lost PR expression, which limits the clinical application of progestin-based therapy. While the idea that restoring PR expression will resensitize tumors to progestin was proposed over 20 years ago, we only now have the molecular tools to accomplish this goal. Basic science research has revealed several pathways that govern the expression of PR at the DNA, RNA, and protein levels. In this article, we describe one current approach to restore expression of PR at the epigenetic level in endometrial cancer. While still in the preclinical stage, we believe this strategy to re-establish PR expression will result in resensitization of endometrial tumors to progestin therapy. ... Read more

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