George Kumar: Link Between Hormone Sensitivity and Tumor Phenotype in Women
George Kumar, Senior Director at AstraZeneca, shared on LinkedIn:
“New Study Highlights Link Between Hormone Sensitivity and Tumor Phenotype in Women
Research recently published in Nature, introduces a novel concept: hormone sensitivity shapes tumor cell phenotype and aggressiveness, particularly in women. The authors identified an integrated pro-tumor pathway that may be more active in female patients and demonstrated that targeting a G-protein-coupled receptor (GPCR) – with drugs not traditionally used in oncology – could be effective against E-cadherin–dependent cancers.
This work underscores the importance of sex-specific factors in cancer biology and treatment, and offers a path toward more precise, personalized, and equitable cancer care.
Figure Courtesy: Nature. Vol 643, 17 July 2025
Figure 1 | Risk of skin cancer in premenopausal women. a, Levels of the sex hormone oestradiol tend to be high in women between the ages of about 15 and 55, but remain low in men throughout life.
Raymond et al.6 found that incidences of several cancers in non-reproductive tissues, such as the skin cancer melanoma, were higher for female individuals during this period of high oestradiol levels than for male individuals of the same age. (Adapted from Fig. 1 of ref. 6.) b, The authors discovered that oestradiol promotes tumour growth and spread (metastasis) when expression of the protein E-cadherin is lost – an event that often happens in cancer.
Loss of E-cadherin increases expression of the oestradiol receptor ERα. When bound to oestradiol, ERα stimulates transcription of the receptor protein GRPR. Activation of GRPR by its ligand GRP reinforces suppression of E-cadherin and mediates pro-metastatic transcriptional programs. Solid and dashed lines represent transcriptional regulation that is reinforced or lost, respectively, in this scenario.”
Title: Targeting GRPR for sex hormone-dependent cancer after loss of E-cadherin
Authors: Jérémy H. Raymond, Zackie Aktary, Marie Pouteaux, Valérie Petit, Flavie Luciani, Maria Wehbe, Patrick Gizzi, Claire Bourban, Didier Decaudin, Fariba Nemati, Igor Martianov, Irwin Davidson, Catherine-Laure Tomasetto, Richard M. White, Florence Mahuteau-Betzer, Béatrice Vergier, Lionel Larue and Véronique Delmas
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