However,
Discovery link between sex hormones:
A team from the Institut Curie. Consequently, Inserm and CNRS[1] has highlighted a new molecular mechanism, hitherto unknown, linking estrogens (female sex hormones) to the worsening of certain cancers not conventionally considered as hormone-dependent, such as the melanomagastric cancer or even thyroid cancer.
These works, published in Nature On June 11, 2025, opened the way to new therapeutic strategies, especially for women of childbearing age.
Transverse cut of melanoma with the MTA CD163+ (macrophages associated with tumors) colored in green. Therefore, the blood vessels colored in red and the nucleus of the cells colored in gray. For example, © 2019 ETZERODT et al.
A hormonal role in long-term cancer – Discovery link between sex hormones
While it is admitted that hormone-dependent cancers represent approximately 20 % of cases. Furthermore, discovery link between sex hormones of cancer worldwide[2]this new study questions this inventory. In addition, Based on a vast epidemiological analysis. Furthermore, researchers have found that several cancers, including melanoma, are more frequent in women between puberty and menopause than in men at the same age, period marked by strong exposure to estrogens.
“Empirically, dermatologists already noted a higher impact of melanoma in young women, especially after pregnancy. Meanwhile, We have sought to scientifically understand this phenomenon“explains Dr. Meanwhile, Lionel Larue, director of research at Inserm, team leader at theCurie Institute and the leader author of the study.
Unprecedented pro-metastatic molecular loop – Discovery link between sex hormones
The analyzes carried out made it possible to identify a way of previously unknown signaling. Similarly, strictly dependent on the female hormonal environment. This regulation loop implies different key molecular actors including ESR1 (the estrogen receiver) which induces the GRPR receptor (for Gastrin-releasing peptide receptor). causing theactivation of the pro-metastatic route discovery link between sex hormones YAP1[3] which represses e-cadherin (ECAD), a molecule d’membership cell cell whose decrease facilitates tumor progression. The loop is closed by the induction of the transcription of ESR1 after reducing the level of ECAD.
Thus. this mechanism promotes the growth of tumors, migration and invasion of tumor cells, as well as their resistance to anoikis[4] – A process of a cell death normally involved in the prevention of metastatic dissemination. And it is a particularly active process in women, since depending on the activation of the ESR1 receptor by estrogens.
A new promising therapeutic target
Remarkable. GRPR belongs to the family of receptors coupled with G (RCPG) proteins, which represent 35 % of the targets of drugs currently approved, but remain under-exploited in oncology. By administering specific GRPR antagonists in preclinical models, researchers have observed a significant reduction in the formation of metastases.
In addition to his involvement in tumor progression, discovery link between sex hormones GRPR also plays a role in the perception of pain. Its modulation could therefore brake metastases both to improve the quality of life of patients. The implementation of anti-estrogenic combinatorial therapies could constitute a relevant approach in the treatment of melanomas. and other cancers, presenting this metastatic loop.
Age. sex at the heart of personalized medicine tomorrow
This major discovery highlights a new facet of sex inequalities in the face of cancer and highlights the importance of better integrating hormonal and biological factors in prevention, diagnosis and treatment. It also offers new perspectives to redirect existing drugs to use in oncology.
“Better understanding the impact of sex and age on the development of certain cancers is essential to advance precision medicine. This work sets the basics of innovative therapeutic approaches, prevalent to women, and opens up concrete clinical perspectives“, Concludes Dr. Lionel Larue, research director at Inserm.
Notes:
[1] These works were carried discovery link between sex hormones out by Dr. Lionel Larue. research director at Inserm, head of the normal and pathological development team of melanocytes in the signaling, radiobiology and cancer unit (Institut Curie, Inserm, CNRS, University Paris Saclay) and Dr Véronique Delmas, director of research at CNRS in the same team.
[2] Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA CANCER J CLIN 71, (2021).
[3] The YAP-1 route is an essential cellular mechanism that regulates the growth and survival of cells. His dysfunction is involved in several diseases, including cancer, making it a promising target for new therapies.
[4] Anoikis is a programmed cell death process that occurs when cells lose their anchoring to their environment. This mechanism is crucial for maintaining tissue homeostasis. plays an important role in embryonic development, healing of wounds and prevention of tumors.
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