Mechanisms of Cancer-Directed Therapies

Cancer has been prevalent for centuries and humans have been concerned with the treatment of cancer for a seemingly equal time. Breast cancer was first described thousands of years ago and was first reported to be treated with surgery in 500 BCE. In the 18th and 19th centuries, surgical resection for the treatment of cancer started to gain popularity, but it was only in the early 1900s that chemotherapy entered the picture. It was post-World War II that chemotherapy began to become widely used with cures of leukemia and lymphoma described in the 1960s. While oncologists became the purveyors of chemotherapy, they equally began managing complications of these same treatments. Thus, a mechanistic understanding is essential to the prediction and treatment of complications stemming from cancer-directed therapies.

CATEGORIES OF CANCER-DIRECTED THERAPY

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Cytotoxic chemotherapy: The term chemotherapy arises from the concept of treating disease with chemicals. Traditional chemotherapy was developed in the early 1900s and is still a part of the treatment program for most cancers. Some common types of chemotherapy include pyrimidine analogs, purine analogs, anthracyclines, antifolates, alkylating agents, platinum derivatives, DNA topoisomerase inhibitors, taxanes, vinca alkaloids, hypomethylating agents, and proteasome inhibitors, among others.
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Targeted therapy: Targeted therapies come in various forms but are generally monoclonal antibodies or small molecules that interact with a specific molecule known to be implicated in cancer growth. Some examples include imatinib targeting BCR-ABL, bevacizumab targeting VEGF, trastuzumab targeting HER2, and erlotinib targeting EGFR, among an ever-increasing number of drugs.
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Immunotherapy: Immunotherapy is a relatively new form of cancer-directed therapy, encompassing vaccine, cellular, cytokine, anti-CTLA-4, and anti-PD-1 therapies. Examples of the most commonly used therapies are pembrolizumab, ipilimumab, and nivolumab.
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Radiation therapy: Radiation therapy can be divided into two types, based on the source of radiation. External beam radiation refers to radiation in which the source comes from outside the patient. Internal beam radiation, also known as brachytherapy, refers to radiation in which the source is placed next to, or within, a tumor. Complications from radiation therapy arise from radiation exposure to non-tumor cells and are based on the type and location of cells that are affected.