Is metastatic cancer a battle already lost?

Metastasis remains the leading cause of cancer-related deaths, yet our grasp on this complex process and its treatment is still evolving. Tumor cells first invade surrounding tissues and enter the bloodstream or lymphatic system. Here, circulating tumor cells (CTCs) face numerous challenges, including immune attacks and oxidative stress. Only a few survive to colonize distant organs, where they may enter a state of dormancy, undetectable and resistant to conventional therapies. The reactivation of these dormant cells leads to clinically evident metastases, which are difficult to treat and often resistant to current therapies.
Technological advances in next-generation sequencing have revolutionized our understanding of metastasis. These tools have uncovered the genetic and phenotypic diversity of metastatic tumors, highlighting the evolutionary pressures and adaptive mechanisms cancer cells use to thrive in new environments. Despite these insights, metastasis-specific therapies remain elusive. Recent research focuses on the tumor microenvironment (TME), which plays a critical role in supporting metastatic growth and immune evasion. By co-opting immune and stromal cells, metastatic cells create a supportive niche that promotes their survival and growth. Innovative treatments targeting the unique interactions within the TME are showing promise in preclinical studies.
Promising new treatments are emerging, aiming to tackle the adaptive nature of metastatic cancer. For instance, targeting the SLC6A8 phosphocreatine transporter in colorectal liver metastases shows potential, and liver-directed therapies like hepatic artery infusion chemotherapy have demonstrated survival benefits. Moreover, understanding and targeting the plasticity of metastatic cells could constrain their evolutionary space, making them more vulnerable to treatments. Single-cell profiling and spatial genomics are expected to further refine these approaches, offering hope for more effective therapies.