About this Research Topic
Endocrine-related cancers originate from endocrine organs, such as thyroid, pituitary, hypothalamus, adrenal cortex, pancreas, primary and secondary sex organs and mammary glands (breast). Cancers of the breast, ovary, prostate and endometrium are steroid-dependent, with breast cancer being the most common among women and prostate cancer being the third among men. Since both of these cancer types require steroid hormones for their growth, survival and proliferation, a strategy, known as endocrine therapy, that blocks the synthesis or actions of the key steroid hormones, has been adapted as the first line-of-treatment. However, eventually a majority of the endocrine-related cancers evolve into a hormone-independent phenotype, rendering the endocrine therapies ineffective (decrease in efficacy of second-line therapy to 30% from the 70% efficiency for the first-line treatment). Once this refractoriness sets in, these turn into very aggressive cancers. Adaptive as well as primary resistance to endocrine therapy remain a persistent clinical challenge.
Over the last decade or so, many research groups have been trying to understand the mechanism of resistance to endocrine therapies and develop more effective treatment strategies with minimum toxicity. Among several well-known modes of endocrine therapy resistance, de novo mutations in the hormone receptor ESR genes are seen in resistant cancers, but in a rare percentage of cases. Differential activation of signaling pathways such as PI3K/AKT and Ras-MAPK is seen more often in tumors with acquired resistance. Alterations in cell cycle regulators such as Cyclin D1, RB or MYC and activation of receptor tyrosine kinases (examples ErbB2, FGFR, IR, IGF1R) are also implicated in development of endocrine therapy resistance. More recently, enhanced autophagy has been associated with acquisition of endocrine-therapy resistance.
In this Research Topic of Frontiers in Endocrinology, we have made an attempt to provide a comprehensive picture of the challenges faced due to emergence of resistance to endocrine therapies in breast cancer and the measures taken by the medical community to avoid/overcome such setback. It also brings the research findings from various groups across the world together providing a most updated, thorough understanding of the basis of resistance. Given that prostate cancer exhibits a lot of similarities in terms of their response to steroid hormones, mechanistic studies from endocrine therapy resistance in prostate cancer field are also included. We hope that this collection of research articles will provide a comprehensive insight into the current status of endocrine therapy to the clinicians, academics as well as patient communities.
We welcome original as well as review articles on a broad range of topics related to the resistance to endocrine therapies in cancer, which may include clinical as well as molecular studies.
Potential topics include, but are not limited to:
1. Possible molecular mechanisms underlining resistance to endocrine therapy in breast, ovary, prostate and endometrium cancers.
2. Cross-talk among endocrine and other non-endocrine (example GF) signaling pathways contributing to endocrine drug resistance and strategies to overcome these
3. Possible role of biomarkers that may be useful to predict resistance or response to targeted agents.
4. Role of altered metabolism on endocrine resistance
5. Cancer stem cells and endocrine resistance
6. Role of hypoxia in endocrine resistance
7. The potential role of microenvironment in the acquisition of endocrine-therapy resistance
8. Genomic and Non-genomic pathways of steroid hormones and role in endocrine resistance
9. Exosomes in endocrine therapy resistance.
10. Application of genome editing in combating endocrine therapy resistance.
11. Liquid biopsy as an early predictor of endocrine therapy resistance.
12. Chemotherapy-induced senescence and its impact on endocrine therapy success.
13. Non-coding RNA in endocrine therapy resistance.
14. Chromatin alterations and endocrine therapy resistance
15. Implications of autophagy on endocrine resistance
Keywords: Steroid dependent, Endocrine therapy, Growth factor signaling, Hormone ablation, Non-genomic
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.