Both health care professionals and patients regularly refer to systemic oncology treatments as “chemo”, although every month this term becomes less representative. Some medications clearly fit into certain categories: cisplatin & methotrexate (traditional chemotherapy), imatinib & bevacizumab (targeted), and nivolumab & pembrolizumab (immunotherapy). For other medications, classification can be less clear based on mechanism of action, discovery technology, historical context, and manufacturing technique. Consider more nuanced examples like abiraterone, asparaginase, bacilli Calmette-Guerin (BCG), brentuximab vedotin, lenalidomide, lutetium Lu 177 dotatate, and trabectedin. The National Cancer Institute’s (NCI) website has a comprehensive dictionary of cancer-related terms as well as various articles on types of cancer treatment. Their definitions are summarized below.

Traditional chemotherapies are cytotoxic, categorized by their effects on the cell cycle, and often act on fast-growing malignant and normal cells. Alternatively, hormone therapies specifically affect cells that are dependent on endocrine signaling for growth and are especially effective for the majority of breast and prostate cancers (Types of Cancer Treatment).

Defining targeted therapy can be particularly daunting, as all medications have targets and “targeted” therapies have off-target effects. These medications evolved from advancements in immunology, cell biology, and molecular biology, enabling an understanding of key genes and enzymes responsible for regulating cell growth (Falzone, 2018). The NCI states that targeted therapies are developed to interact with a specific cancer-associated molecular target and may exert a cytostatic or cytotoxic effect. Imatinib, a tyrosine kinase inhibitor (TKI), is the prototypical example of a small-molecule targeted therapy and was developed to target the BCR-ABL fusion kinase that is critical to chronic myeloid leukemia pathogenesis (Falzone, 2018). Although many targeted small-molecule drugs act on kinases, there are a range of other targets including proteasomes that degrade cellular proteins, and poly ADP-ribose polymerases (PARP) that aid in DNA repair. Protein drugs are typically much larger than their “small-molecule” counterparts, and the majority are monoclonal antibodies (mAbs) that bind to transmembrane receptors or ligands. By binding with their targets, mAbs can block oncogenic signaling as well as cause cell lysis. Additionally, extremely potent cytotoxic payloads can be conjugated to these proteins to deliver chemotherapy to a target-expressing cancer cell (Types of Cancer Treatment). 

Immunotherapy is a broad term encompassing all therapies which stimulate the immune system. Immune checkpoint inhibitors, such as the anti-programmed death (PD)-1 and anti-PD ligand-1 (PD-L1) mAbs, are targeted immunotherapies that “take the brakes off” of the immune system, increasing immune clearance of malignant cells. Cellular therapies have been developed from dendritic cells and chimeric antigen receptor T cells (CAR Ts), while therapies developed from other cell lines are in development. When patients are treated with CAR T cells, such as tisagenlecleucel and axicabtagene ciloleucel, their T cells are modified and expanded ex vivo to specifically target an antigen. Vectors include viruses and plasmids that are genetically modified to induce expression of proteins in cancer cells, eliciting a cytotoxic or immune response. Within the definition of immunotherapy, the NCI also includes cytokines, immunomodulatory drugs (e.g., thalidomide and analogs) and mAbs that activate the immune system through antibody-directed cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and other mechanisms (e.g., rituximab, blinatumomab). The myriad of treatments produced from living organisms are referred to as biotherapies, regardless of their mechanism or other classifications (Types of Cancer Treatment, not depicted in figure 1). 

Figure 1. Classification of oncology medications, depicting overlapping classes. Not drawn to any scale.

catchemo

mAb = monoclonal antibody

 

We classify the aforementioned examples as follows, per the NCI definitions: 

  • Abiraterone (targeted small-molecule hormone therapy). 
  • Asparaginase (targeted protein)
  • BCG (immunotherapy)
  • Brentuximab vedotin (antibody-drug conjugate)
  • Lenalidomide (immune modulator)
  • Lutetium Lu 177 dotatate (targeted radionuclide hormone therapy)
  • Trabectedin (traditional chemotherapy)

There are certainly other difficult-to-classify medications as well as some categorical gray areas. Thalidomide, for example, was not designed with the intent to treat cancer, but still fits best within the immunomodulator category, which also fits best as a subset of immunotherapy and targeted therapy. Additionally, the NCI definitions classify trastuzumab as a targeted immunotherapy because it enables ADCC. However, in our practice we generally find its “immunotherapy” classification convoluting in the era of immune checkpoint inhibitors. 

Given the rate of innovation in oncology, we may need to publish updates!

References

NCI Dictionary of Cancer Terms. Retrieved from https://www.cancer.gov/publications/dictionaries/cancer-terms 

Types of Cancer Treatment. Retrieved from https://www.cancer.gov/about-cancer/treatment/types

Falzone, L., Salomone, S., & Libra, M. (2018). Evolution of cancer pharmacological treatments at the turn of the third millennium. Frontiers in pharmacology, 9, 1300.

 

Written By:

  1. Tyler Redelico, PharmD, BCOP
  2. Clinical Pharmacist
  3. MD Anderson at Cooper University Hospital 
  4. Camden, NJ

Christina Zelasko, PharmD, BCPS
Investigational Drug Pharmacist 
MD Anderson at Cooper University Hospital
Camden, NJ

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