Ras-proximate-1 (RAP1): a prognosis and therapeutic target in the metastatic spread of breast cancer

Abstract

Breast cancer (BC), a highly heterogeneous disease, has demonstrated a gradual increase in both incidence and mortality rates. At present, it has become one of the most common malignant tumors and the main cause of cancer death worldwide. While early screening is recognized as an effective preventive and therapeutic measure for BC, the disease continues to exhibit a high rate of metastasis. Metastatic BC is still the main cause of poor prognosis and death of patients, necessitating urgent investigation and resolution. Among the various metastatic sites of BC, bone metastases warrant particular attention due to their prevalence. In numerous studies on BC bone metastasis mechanisms, cancer markers have been shown to significantly influence the pattern and extent of BC metastasis and dissemination. In the tumor microenvironment, Ras-proximate-1 (RAP1), a GTPase protein, is not only upregulated in various malignant tumors and bone-related diseases, including BC, but also regulates migration, invasion, distant metastasis, and other signaling pathways in numerous malignant tumor cells, including BC as well. Despite these findings, there remains a paucity of advanced research and discussion on the relationship between RAP1 and BC bone metastasis. Furthermore, no clinically approved RAP1-related inhibitors for BC bone metastasis are currently available. Nevertheless, RAP1 and its associated signaling molecules represent potential molecular targets for the prevention and treatment of BC bone metastasis, warranting further investigation. Therefore, this article provides a comprehensive review of RAP1's pathogenic role in BC bone metastasis, emphasizes RAP1 and its associated signaling pathways, and summarizes current research on natural compounds and extracts that modulate BC bone metastasis via RAP1 or RAP1-related signaling pathways. This review aims to offer novel perspectives for developing RAP1 as a potential molecular target in the prevention and treatment of BC bone metastasis, as well as for the development of related therapeutic agents.

Keywords: Bone metastasis; Breast cancer; Inflammation; Microenvironment; Ras-proximate-1; Treatment.