Tumor Microenvironment, Clinical Features, and Advances in Therapy for Bone Metastasis in Gastric Cancer

SIMPLE SUMMARY: Bone metastasis in gastric cancer (GC-BM) has received little attention because of its rarity, but the increased pain and shortened survival of patients due to the bone destruction and skeletal-related events (SREs) caused by tumors cannot be ignored. Immune cells and molecules such as RANK-L and GFs in complicated bone microenvironments create suitable conditions for tumor cells to proliferate and break the balance of bone circulation, which leads to osteolysis and osteogenesis. Bone radionuclide scans now are the most sensitive examination for diagnosing bone tumors, and bone-related alkaline phosphatase (ALP) also shows a certain significance in the diagnosis of bone tumors. Combined application of chemotherapeutic drugs, targeted drugs, and immune drugs are the main treatments of GC-BM. This review paper intends to discuss the clinical status of GC-BM, as well as its possible molecular pathogenesis pathways and therapeutic options. ABSTRACT: Gastric cancer (GC) is one of the most malignant neoplasms worldwide, accounting for about 770,000 deaths in 2020. The incidence of gastric cancer bone metastasis (GC-BM) is low, about 0.9–13.4%, and GC patients develop GC-BM because of a suitable bone microenvironment. Osteoblasts, osteoclasts, and tumor cells interact with each other, secreting cytokines such as PTHrP, RANK-L, IL-6, and other growth factors that disrupt the normal bone balance and promote tumor growth. The functions and numbers of immune cells in the bone microenvironment are continuously inhibited, resulting in bone balance disorder due to the cytokines released from destroyed bone and growing tumor cells. Patients with GC-BM are generally younger than 65 years old and they often present with a later stage of the disease, as well as more aggressive tumors. They usually have shorter overall survival (OS) because of the occurrence of skeletal-related events (SREs) and undetected bone destruction due to the untimely bone inspection. Current treatments of GC-BM focus mainly on gastric cancer and SRE-related treatment. This article reviews the clinical features, possible molecular pathogeneses, and the most commonly used diagnostic methods and treatments of bone metastasis in gastric cancer.