[A transition from targeting immune evasion to a multidisciplinary collaborative treatment framework for "homotherapy for heteropathy" in liver metastases].

Abstract

Liver metastasis is a common and challenging clinical problem in the progression of various solid tumors. The current diagnostic and therapeutic scheme is primarily formulated according to the pathological classification and molecular stratification of the primary tumor. However, once tumors of different origins metastasize to the liver, they may face common challenges such as limited benefit from immune checkpoint inhibitors, inadequate and unsustained disease control with systemic therapy, and recurrence following local treatment. The liver's immunologically tolerogenic background, together with impaired antigen presentation, restricted effector immune responses, myeloid-mediated immunosuppression, abnormal vasculature, stromal remodeling, and metabolic competition, may contribute to organ-specific therapeutic resistance that is shared across different cancer types after hepatic metastasis. Based on a review of relevant mechanisms, clinical evidence, and limitations of existing treatment paradigms, a clinical decision-making framework for "homotherapy for heteropathy" in liver metastases is proposed. Systemic therapies-including chemotherapy, targeted therapy, and immunotherapy-are integrated with local therapies, including surgery, ablation, interventional therapy, and radiotherapy, together with supportive care to address potentially shared organ-specific therapeutic resistance following liver metastasis in line with standardized classification and treatment of the primary tumor. Treatment is dynamically adjusted according to disease status and treatment response, with the integration and implementation of systemic and local therapies, therapeutic goals, and treatment sequencing. This framework is primarily applicable to patients with resectable or amenable-to-ablation oligometastatic disease, initially unresectable disease with the potential for conversion to resectability, liver-dominant disease with stable extrahepatic disease, and patients with limited residual intrahepatic disease or oligoprogression following systemic therapy. Clinical applications should still consider the biological characteristics of the primary cancer, the status of liver and extrahepatic disease, prior treatment responses, liver function reserve, and the available evidence base. The "homotherapy for heteropathy" framework uses shared organ-specific therapeutic resistance as an entry point-based on cancer-specific treatments-to facilitate patient stratification, multidisciplinary collaboration, and the optimization of treatment sequencing. In the future, domestic multicenter prospective studies and real-world cohorts will be needed to further clarify the suitable patient population, treatment timing, and biomarkers of benefit.