Cancer Metastasis: Therapeutic Challenges and Opportunities.

Abstract

Metastatic cancer is the leading cause of cancer-related mortality, responsible for nearly 90% of deaths worldwide. Its progression depends on a multistep cascade involving invasion, vascular dissemination, survival in circulation and colonization of distant organs. This process is highly inefficient yet devastating, as a small fraction of tumor cells can establish lethal secondary lesions. This review summarizes recent advances in understanding the biological complexities of metastasis, including tumor heterogeneity, chemoresistance and the tumor microenvironment. We further examine emerging diagnostic and therapeutic strategies, spanning molecular profiling, liquid biopsies, nanomedicine, immunotherapy and artificial intelligence. Targeted therapies toward inhibiting metastasis such as BRAF/MEK inhibitors have extended progression-free survival by 30-40% in melanoma trials, while checkpoint inhibitor combinations (PD-1 and CTLA-4) achieve response rates exceeding 50% in melanoma and renal cell carcinoma. Liquid biopsy platforms enable real-time detection of resistance mutations, and nanoparticle-based drug delivery systems improve drug accumulation at tumor sites. Emerging tools such as organoids and tumor-on-a-chip models enhance predictive accuracy, while AI-driven analytics integrate multi-omics data to refine patient stratification. Integrating these innovations into next-generation clinical trials will require biomarker-driven patient selection, multi-center validation of assays and regulatory frameworks to accelerate approval. Together, these advances represent a transition toward personalized and adaptive care, offering the potential to redefine metastatic cancer as a manageable condition rather than a terminal diagnosis.