Metabolic Dysregulation Controls Endocrine Therapy–Resistant Cancer Recurrence and Metastasis

Abstract

Cancer recurrence and metastasis involves many biological interactions, such as genetic, transcription, environmental, endocrine signaling, and metabolism. These interactions add a complex understanding of cancer recurrence and metastatic progression, delaying the advancement in therapeutic opportunities. We highlight the recent advances on the molecular complexities of endocrine-related cancers, focusing on breast and prostate cancer, and briefly review how endocrine signaling and metabolic programs can influence transcriptional complexes for metastasis competence. Nuclear receptors and transcriptional coregulators function as molecular nodes for the crosstalk between endocrine signaling and metabolism that alter downstream gene expression important for tumor progression and metastasis. This exciting regulatory axis may provide insights to the development of cancer therapeutics important for these desensitized endocrine-dependent cancers.

Lactate Metabolism and Immune Modulation in Breast Cancer: A Focused Review on Triple Negative Breast Tumors

“…Although this review focuses on TNBC, it is important to note that endocrine-resistant luminal breast cancer and trastuzumabresistant HER2+ breast cancer also exhibit metabolic reprogramming, whereby the glycolysis rate and associated lactate acidosis are increased (17,(171)(172)(173). Hence, in analogy with the observed metabolic changes in TNBC, it is likely that the glycolytic TME in treatment-resistant luminal and Her2+ tumors could disrupt immune surveillance and negatively affect the response to immunotherapy.…”

Grand Challenge in Medical and Surgical Rehabilitation: From Mechanisms to Evidence Based Rehabilitation Programs

“…On the other hand, most non-specific symptoms are related to autonomous regulation, namely, the hypophysis-pituitary-adrenal axis (29). Last but not least, specific hormonal dysregulation (e.g., in cancer) and mediators (e.g., in chronic widespread pain) are involved (30)(31)(32). As non-specific symptoms may have a major impact on quality of life and hinder participation, rehabilitation must focus on these.…”

Mitochondrial nanotargeting in malignancies (Review)

“…Even so, patients tolerate hormone therapy better than chemotherapy. Due to the fact that some tumors do not present hormonal receptors, they will not respond to this therapy, thus a vigorous selection of the patients must be made (14).…”

“…Therefore, new therapeutic approaches must be explored, aiming for improved efficacy, minimal side effects and a minimal cost of production. The need to establish a personalized medicine as a mean of providing targeted delivery of the therapeutic substances based exactly on the type of cancer that each patient has become acute (1,(11)(12)(13)(14)(15).…”