by Endocrine therapy drugs (ETDs) have emerged as an important tool in modern cancer treatment. These drugs work by targeting the hormonal pathways that fuel some cancer growth. In this article, we will explore the different types of ETDs, how they work, the cancers they treat and the latest advances in this promising field of cancer research.
Tamoxifen and Aromatase Inhibitors
One of the earliest and most commonly used ETDs is tamoxifen, approved in the late 1970s. Tamoxifen works as an estrogen receptor modulator or SERM. It binds to estrogen receptors on breast cancer cells and blocks the effects of estrogen, which can promote the growth of some breast cancers.
Tamoxifen revolutionized breast cancer treatment and became the standard first line ETD for estrogen receptor positive breast cancer. It reduces the risk of recurrence and improves survival. However, some limitations were discovered over time such as potential serious side effects like an increased risk of uterine cancer and blood clots.
In the 1990s, a new class of ETDs called aromatase inhibitors were developed. Aromatase is the enzyme that produces estrogen. Aromatase inhibitors work by blocking the aromatase enzyme and lowering estrogen levels in postmenopausal women. The three FDA approved types are anastrozole, letrozole, and exemestane.
Aromatase inhibitors are now considered a more effective option than tamoxifen as first line therapy in postmenopausal women. They provide better outcomes with fewer side effects compared to tamoxifen. While tamoxifen is still useful in premenopausal women or as a switch therapy after tamoxifen, aromatase inhibitors are the standard of care for most postmenopausal women with hormone receptor positive breast cancer.
Prostate Cancer Treatment
For prostate cancer, androgen deprivation therapy or ADT using drugs like Lupron is a mainstay of treatment. Prostate cancer growth is fueled by male hormones called androgens, mainly testosterone. Lupron and similar gonadotropin-releasing hormone (GnRH) agonists work by shutting down testosterone production in the body, thereby depriving the cancer cells of the growth signals they need.
ADT has proven effective for lowering PSA levels and shrinking tumors, both as primary therapy for advanced disease and as an adjunct to radiotherapy in earlier stage prostate cancer. However, ADT treatment is not curative and most prostate cancers will eventually become castration-resistant, at which point additional anti-androgen drugs may provide benefit. Enzalutamide and abiraterone are two newer anti-androgen medications that have significantly extended survival for men with metastatic castration-resistant prostate cancer.
Other Cancers Treated with ETDs
In addition to breast and prostate cancer, select other hormone-driven cancers also respond well to ETDs. Ovarian cancer growth is stimulated by estrogen in some cases. Tamoxifen has shown benefits for recurrent or advanced ovarian cancer, particularly in combination with chemotherapy.
For endometrial cancer or uterine cancer, aromatase inhibitors and mifepristone (an antagonist of the progesterone receptor) may provide options beyond standard chemotherapy or radiation. Mifepristone is approved for advanced or recurrent endometrial cancer.
In rare pediatric cancers like juvenile granulosa cell tumor of the ovary, androgenic hormones play a role so gonadotropin suppression with drugs like leuprolide can induce remissions.
Thyroid cancer may also respond to ETDs in select cases, if the growth is fueled by excess levels of thyroid stimulating hormone (TSH). Drugs that suppress TSH levels have helped control some advanced, differentiated thyroid cancers.
Research Advances and the Future
Research into new ETDs and combinations continues at a rapid pace. More selective estrogen receptor degraders (SERDs) and targeted protein degraders are being studied which may improve upon SERMs and aromatase inhibitors.
Combining ETDs with immunotherapies is an exciting area of investigation that may lead to synergistic effects against certain hormone driven cancers. Trials exploring ETD and checkpoint inhibitor combinations are underway.
As we continue elucidating the complex hormonal pathways involved in cancer, newer drug targets are emerging. Medications affecting signaling through the insulin-like growth factor pathway or targeting virally mediated androgen receptors hold promise. Advances in precision oncology may also help identify new subsets of patients most likely to benefit from specific ETDs.
Conclusion
ETDs have changed the landscape of cancer treatment over the last few decades. Continued research offers hope to expand their uses and improve outcomes even further. As we gain a deeper understanding of cancer biology, endocrine therapies will remain at the forefront of personalized care for hormone receptor positive cancers. With further advances, many patients may be able to benefit from these well-tolerated targeted drugs.
