Mechanism of TGFβ in Bone Metastases and its Potential Therapeutic Uses

Complications associated with advanced cancer pose a clinical challenge, particularly when bone metastases are involved, as they can worsen the prognosis and reduce the patient’s chances of survival. Solid tumors, such as those originating from the breast, prostate, and lungs, can potentially metastasize to bone. Mineralized bone matrices contain potent growth factors and cytokines. The bone microenvironment is distinctive, furnishing prolific soil for cancer cell proliferation. Following tumor-induced bone destruction by osteoclast, the Transforming Growth Factor (TGFβ) is released from the mineralized bone matrix. It is one of the most abundant growth factors released from the bone matrix. TGFβ stimulates tumor cell secretion of factors that accelerate bone resorption and stimulate tumor cell colonization. Consequently, TGFβ is essential for fueling cancer’s vicious cycle of cancer growth and bone destruction. In addition, TGFβ promotes Epithelial-Mesenchymal Transition (EMT), increasing cell invasiveness, angiogenesis, and metastasis progression. Emerging evidence demonstrates that TGFβ inhibits immune responses, allowing opportunistic cancer cells to evade immune checkpoints and promote bone metastasis. By inhibiting TGFβ signaling pathways, cancer progression in the bone could be broken, EMT could be reversed, and immune response could be improved. However, the dual function of TGFβ as both a tumor suppressor and an enhancer pose a formidable obstacle to developing therapeutics that target TGFβ signaling. This review delves into the significance of TGFβ in the advancement of cancer and bone metastases, in addition to examining the current therapeutic prospects of TGFβ pathway targeting.