Figure 1.

Chemotherapy or radiotherapy induces a metastasis-receptive microenvironment in various organs. One of the unwanted side effects of treatment is upregulation of several pro-metastatic and pro-survival factors, such as chemokines (e.g., SDF-1), growth factors (HGF/SF and VEGF), bioactive sphigophospholipids (S1P and C1P), and alarmines (ATP and UTP) in collateral-damaged tissues and organs. In parallel, in response to tissue damage, proteolytic cascades, such as the coagulation cascade (CoaC), complement cascade (ComC), and fibrynolytic cascade (FibC), are activated, which in different ways also enhance the metastasis of cancer cells that survived treatment. These most-resistant-to-therapy, and thus surviving, cancer cells are usually endowed with high endogenous motility. This mechanism plays an important role, primarily in metastasis of malignant cells to the tissues susceptible to the toxic effects of chemotherapy or radiotherapy, such as bones, lungs, liver and abdominal and pelvic cavities.