Researchers have shown that autocrine human prolactin (hPRL) promotes endometrial tumor growth and metastasis, as well as reduces sensitivity to chemotherapy, leading to worse survival outcomes. Based on this association, the investigators also point to a possible therapeutic strategy for endometrial cancer (EC). The results were published recently in Endocrinology.
The team, led by Peter E. Lobie, MD, PhD, of the National University of Singapore, and Tao Zhu, MD, PhD, of the University of Science and Technology of China in Hefei, note that treating late-stage EC) remains a major challenge, with poor response to chemotherapy and low patient survival rate. They have built on earlier studies, which reported elevated serum hPRL levels in EC tumours, by further delineating the functional roles of hPRL in EC progression. ”
For this study, they show that autocrine hPRL expression stimulated EC cell proliferation, invasion and migration, and promoted tumor growth and metastatic colonization in xenograft models. “In addition,” the authors write, “forced expression of hPRL decreased sensitivity of EC cells to chemotherapeutic drugs (i.e., doxorubicin and paclitaxel), both in vitro and in vivo.”
Consistently, they show that depleting hPRL significantly reduced oncogenicity and enhanced the sensitivity to chemotherapy. Therefore, the researchers propose that targeting prolactin signaling could be considered as a viable adjuvant therapy in late-stage EC to improve the response to chemotherapy.
A companion piece written by Felicitas Lopez Vicchi and Damasia Becu-Villalobos, PhD, of the Instituto de Biología y Medicina Experimental Conicet in Buenos Aires, Argentina, concluded that based on the results of this study, as well as existing literature, “patients with endometrial cancer in advanced stages or with chemoresistance could benefit from anti-PRLR strategies used in combination with actual therapies.”
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