New Study Reveals Sex-Specific Pathway in Melanoma Metastasis

A groundbreaking study conducted by researchers at Institut Curie has unveiled a sex-specific molecular pathway that significantly influences melanoma metastasis, particularly in women. This discovery, which links the loss of E-cadherin to the activation of estrogen receptor-α (ERα) and gastrin-releasing peptide receptor (GRPR), opens new avenues for targeted cancer therapies.

The research, published in the prestigious journal *Nature* on June 23, 2025, highlights the heightened vulnerability of premenopausal women to melanoma, suggesting a critical intersection between hormonal factors and cancer progression. According to Dr. Jérémy H. Raymond, the lead author of the study and a researcher at Institut Curie, “Our findings illustrate how the loss of E-cadherin amplifies the metastatic potential of melanoma cells in a gender-specific manner, emphasizing the need for tailored treatment approaches.”

Historically, cancer research has predominantly focused on male subjects, leading to a significant gap in understanding the unique mechanisms affecting female patients. This study addresses that gap by employing an extensive mouse model to examine the effects of E-cadherin deletion alongside NRAS mutations—common in melanoma. The results revealed that female mice without E-cadherin demonstrated a staggering 63% rate of lung metastasis, in stark contrast to just 16% in their E-cadherin intact counterparts.

The mechanistic insights provided by the study are profound. Loss of E-cadherin resulted in the upregulation of GRPR, a receptor known to facilitate tumor invasiveness. As explained by Dr. Svenja Meierjohann, an expert in oncology at the University of Göttingen, “The overexpression of GRPR in E-cadherin-deficient female melanoma cells underscores a pivotal role in promoting metastatic behavior, which could redefine treatment strategies.”

Furthermore, the study demonstrated that blocking GRPR with pharmacological antagonists, such as RC-3095, effectively reduced metastasis in the mouse models, validating GRPR as a potential therapeutic target. This revelation suggests that existing hormonal cancer therapies, such as the ERα inhibitor Fulvestrant, may also be beneficial in treating melanoma in women.

The implications of this research extend beyond melanoma, prompting a reevaluation of treatment protocols for various cancers traditionally viewed as hormone-independent. Dr. Robert Egan, an oncologist at Johns Hopkins University, remarked, “This study sheds light on the need for a gender-specific lens in oncology, as understanding these pathways could lead to more effective, personalized treatments.”

As the findings continue to resonate within the medical community, they may lead to significant advancements in precision medicine, particularly for female patients with melanoma and other malignancies characterized by E-cadherin loss. The researchers conclude that a targeted approach addressing the identified sex-specific pathways can enhance treatment efficacy and improve outcomes for women battling cancer.

In summary, this research not only enhances the understanding of melanoma metastasis in women but also highlights the broader implications for female cancer treatment, advocating for a shift towards more personalized and gender-sensitive approaches in oncology.