A tumor cell that leaves the first cancer site goes through a journey called the metastatic cascade before successfully forming a new tumor at a distant organ site. Some of the challenges associated with metastasis research, and consequently therapy improvements, lie within the many steps of the metastatic cascade and the different targets within each step. One of the early steps happens when a tumor cell leaves the first tumor site and enters the vasculature system. Here, targets can include inhibiting tumor cells from getting into the bloodstream and inhibiting the blood vessel cells from allowing cells to pass through. Another step happens when a tumor cell stops at another organ site, although research has not yet shown how a tumor cell either decides to or is forced to metastasize to certain organs. Here, we need to answer if it is possible to target all the tumor cells while they are in circulation before they stop at another target, or if it would be better to target the cell in the new microenvironment of the metastasis site. In the final steps of the metastatic cascade, the tumor must contend with the new microenvironment. In a new microenvironment, targets for therapy can include targets also utilized for primary tumors, including forcing tumor cell death or inhibiting tumor cell growth.
The high number of targets in the tumor cell and the microenvironment of the metastatic site, without completely understanding both the metastatic cell and the new microenvironment, make it difficult to pinpoint what it is exactly that we should be targeting to develop therapies. For instance, breast cancer tends to spread to the bone, lungs, liver, and brain, but we do not know when the breast cancer cell decides to leave the primary tumor site. There are some studies that suggest that the cancer cells leave earlier in the primary tumor stage than previously thought (Franken et al. Breast Cancer Research. 2012). In addition, we need more research into how the breast cancer cell decides to which organ it metastasizes. While it was shown that there is a tendency of certain tumor cells to go to specific organs (Fidler. Nat New Biol. 1973), or organotropism, it is still unclear if this tendency is associated completely with a tumor cell’s internal makeup or if organotropism is also influenced by the external forces and interactions between the tumor cell and the new microenvironment. There are many options for targeting available, but further research must be performed to improve efficiency and effectiveness of metastasis treatment.
