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As immunotherapy has joined the ranks of mainstay cancer treatment modalities, biomarkers of response and resistance have become highly sought after. Pretreatment biomarkers have the potential to facilitate rational patient selection, perhaps even for those patients who demonstrate unconventional response patterns such as a delayed response or tumor “progression” before evident regression. Immune-related adverse events, some severe, are also observed with this group of agents. Biomarkers of response could help practitioners avoid exposing patients who are unlikely to respond to these potential immune-related side effects. Additionally, the elevated cost of the therapies is another factor driving intensive study in this area.

For a long time, cancer therapy has had as its sole objective the direct elimination of tumor cells. In case of nonmetastatic disease, this is accomplished by surgery, which removes the primary tumor. Radiotherapy and conventional chemotherapies also aimed at targeting tumor cells preferentially. The high capacity of tumor cells to divide as compared to the normal cells makes them more sensitive to agents that physically, in the case of radiotherapy, or chemically, in the case of chemotherapy, attack DNA and lead to cell death. Chemotherapies targeting mutations in tumor cells such as BRAF have been developed as well. However, these approaches also destroy the nonmalignant cells and have local and/or systemic consequences. To increase specificity toward the tumor cells, cytotoxic agents have been coupled to antibodies that bind to the tumor cells in order to allow their specific targeting to the tumor and not to the normal cells. However, the entry of such constructs into tumors still remains a major issue.