The formation of secondary tumors, or colonization, is the final and often most challenging step in metastasis. Upon arrival at a distant site, cancer cells must extravasate, i.e., exit the circulatory system, and invade the surrounding tissue. The new microenvironment may be hostile, requiring the cancer cells to adapt and establish a supportive niche. This involves interactions with local stromal cells, remodeling of the ECM, and the formation of new blood vessels through a process known as angiogenesis. Successful colonization results in the establishment of a metastatic tumor.