Targeting the triad: phenotypic plasticity, tumor microenvironment and bone microenvironment in prostate cancer bone-metastatic events

The incidence and mortality rates of prostate cancer are increasing annually, indicating that it poses a serious threat to men's health. Previous studies have demonstrated that bone-metastatic tumor cells undergo four hallmark bone-metastatic events, including colonization, dormancy, reactivation and bone reconstruction. However, most advanced patients experience four stages of progression and undergo advanced bone reconstruction—the “vicious circle”—which is irreversible. These patients have a poor prognosis and can even die. Therefore, determining how various components in the tumor and bone microenvironments affect the progression and events of bone metastasis is crucial. Here, we integrate the latest mechanisms of phenotypic plasticity and microenvironment interactions, proposing potential therapeutic targets to disrupt the ‘vicious cycle’ in advanced bone metastasis. We look forward to providing direction and guidance for the future treatment of prostate cancer bone metastasis.