Clinical metastatic cancer from initiation to colonization: emerging challenges and breakthroughs

Area of Science:

• Oncology
• Cancer Biology
• Translational Medicine

Background:

• Metastatic cancer is largely incurable and causes most cancer deaths.
• Current therapeutic strategies often overlook the distinct biology of metastases, focusing instead on primary tumors.
• Understanding metastasis is critical for improving patient outcomes.

Purpose of the Study:

• To provide a comprehensive overview of current knowledge on clinical metastatic cancer.
• To examine the genomic evolution, dissemination, dormancy, colonization, and therapy resistance of metastatic clones.
• To discuss clinical perspectives and emerging technologies for studying metastatic disease.

Main Methods:

• Review of existing literature on cancer metastasis.
• Analysis of genomic evolution in metastatic clones.
• Exploration of organ-specific microenvironmental influences.
• Discussion of single-cell and spatial multi-omics technologies.

Main Results:

• Metastasis involves complex processes including dissemination, dormancy, colonization, and therapy resistance.
• Genomic evolution, including early/late dissemination and treatment-driven selection, shapes metastatic clones.
• Organ-specific microenvironments significantly impact metastatic outgrowth and therapeutic response.
• Wound-healing and regenerative programs are co-opted during metastatic colonization.

Conclusions:

• Treating metastases requires understanding their unique biological features distinct from primary tumors.
• Advances in high-resolution multi-omics technologies are revolutionizing the study of metastatic disease.
• Future research should integrate these insights and technologies for improved clinical strategies against metastasis.