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The Role of Hormonal Receptors in Cancer: Molecular Mechanisms and Targeted Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 679

Special Issue Editor


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Guest Editor
Departamento de Biología de Sistemas, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Campus Universitario, Crtra A2, Km. 33,600, 28805 Alcalá de Henares, Spain
Interests: GHRH; epithelial–mesenchymal transition; prostate cancer; breast cancer; tumor progression; exosomes; angiogenesis; antagonists; cell adhesion; cell proliferation

Special Issue Information

Dear Colleagues,

Understanding the role of hormonal receptors in cancer is paramount for developing effective treatment strategies. Hormonal receptors, such as estrogen and progesterone receptors in breast cancer, play crucial roles in tumor growth and progression. They orchestrate gene expression, fostering cellular proliferation and survival upon activation by their corresponding hormones. In cancers sensitive to hormonal cues, aberrant receptor signaling precipitates unchecked cellular proliferation, thereby fueling tumorigenesis. The molecular mechanisms underlying hormonal receptor activity in cancer involve complex signaling pathways and interactions with other cellular components. The dysregulation of these pathways can lead to resistance to conventional therapies and disease progression. Thus, targeted therapies that specifically inhibit hormonal receptor signaling have emerged as promising treatment options. Various strategies have been devised to target hormonal receptors in cancer. These include hormone receptor antagonists, which block receptor activation, and inhibitors of downstream signaling pathways involved in receptor-mediated tumorigenesis.

Therefore, the aim of this Special Issue, titled “The Role of Hormonal Receptors in Cancer: Molecular Mechanisms and Targeted Therapies”, is to provide novel insights into the molecular action of hormone receptors and new targeted therapies for human cancer. Contributions on these related topics are welcomed, including original research and reviews.

Dr. Laura Muñoz-Moreno
Guest Editor

Manuscript Submission Information

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Keywords

  • hormone receptors
  • cancer
  • cell signaling
  • cancer therapeutics
  • cancer proliferation
  • hormone-sensitive cancers

Published Papers (1 paper)

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Research

27 pages, 5048 KiB  
Article
Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer
by Reetobrata Basu, Prateek Kulkarni, Deborah Swegan, Silvana Duran-Ortiz, Arshad Ahmad, Lydia J. Caggiano, Emily Davis, Christopher Walsh, Edward Brenya, Adeel Koshal, Rich Brody, Uday Sandbhor, Sebastian J. C. M. M. Neggers and John J. Kopchick
Int. J. Mol. Sci. 2024, 25(13), 7438; https://doi.org/10.3390/ijms25137438 (registering DOI) - 6 Jul 2024
Viewed by 528
Abstract
Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy resistance pathways. The growth hormone (GH)–GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer and is overexpressed in PDAC tumors, yet the therapeutic [...] Read more.
Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy resistance pathways. The growth hormone (GH)–GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC. Combinations of gemcitabine with different GHR antagonists (GHRAs) markedly improve therapeutic outcomes in nude mice xenografts. Employing cultured cells, mouse xenografts, and analyses of the human PDAC transcriptome, we identified that attenuation of the multidrug transporter and epithelial-to-mesenchymal transition programs in the tumors underlie the observed augmentation of chemotherapy efficacy by GHRAs. Moreover, in human PDAC patients, GHR expression strongly correlates with a gene signature of tumor promotion and immune evasion, which corroborate with that in syngeneic tumors in wild-type vs. GH transgenic mice. Overall, we found that GH action in PDAC promoted a therapy-refractory gene signature in vivo, which can be effectively attenuated by GHR antagonism. Our results collectively present a proof of concept toward considering GHR antagonists to improve chemotherapeutic outcomes in the highly chemoresistant PDAC. Full article
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