Monoclonal Antibodies (mAbs) and Nomenclature
The foundation of targeted therapy consists of antibodies synthesized by a single clone of cells. The industrial production process involves immunizing rodents, creating immortal cell lines (hybridomas, often based on Chinese hamster ovary cells), and culturing the clones.
Initially, drugs consisted entirely of murine proteins, which caused severe allergic reactions. Genetic engineering led to the development of humanized antibodies, in which murine genes are replaced with human sequences, sharply reducing their allergenicity.
International nonproprietary names (INNs) of mAbs always end in -mab (monoclonal antibody). The stem preceding the suffix indicates the animal source:
- -o- (-omab) — murine;
- -xi- (-ximab) — chimeric (murine variable regions with a human Fc fragment);
- -zu- (-zumab) — humanized;
- -u- (-mumab) — fully human.
Cellular Receptor Blockers (HER2, CD20, EGFR)
Drugs in this group bind to antigens on the cell surface, depriving them of proliferation and survival signals.
- Trastuzumab. A humanized antibody against the HER2 receptor. Administered intravenously for breast cancer (often combined with paclitaxel). A specific severe complication is heart failure.
- Rituximab. The first officially approved chimeric antibody against the CD20 antigen on B lymphocytes. Effective in chronic lymphocytic leukemia (in combination with cyclophosphamide, doxorubicin, etc.). Due to massive cell lysis, it can cause severe tumor lysis syndrome within the first 24 hours, as well as infectious complications.
- Cetuximab and Panitumumab. Block the epidermal growth factor receptor (EGFR), which stimulates metastasis and angiogenesis in solid tumors (e.g., colorectal cancer). Panitumumab is a fully human drug, so it rarely causes infusion reactions, but it may cause acneiform rash and hypomagnesemia.
Angiogenesis Inhibitors
Tumor growth and metastasis critically depend on a dedicated vascular network. The primary stimulus for this process is vascular endothelial growth factor (VEGF).
- Bevacizumab. A humanized mAb that binds the VEGF ligand itself, preventing it from activating its receptors. Used in colorectal, lung, and breast cancer. Due to systemic effects on blood vessels, it can provoke hypertension, thromboembolism (myocardial infarction, stroke), proteinuria, and impair wound healing (up to gastrointestinal perforation).
- Sorafenib and Sunitinib. Classified as small molecules. They act as multikinase inhibitors, directly blocking receptors for VEGF and platelet-derived growth factor (PDGF). Used in renal cell carcinoma and hepatocellular carcinoma.
Tyrosine Kinase Inhibitors and Small Molecules
Unlike large protein antibodies, small molecules are taken orally and are extensively metabolized in the liver by the CYP3A4 enzyme.
- Imatinib. Developed to treat chronic myeloid leukemia and gastrointestinal stromal tumors (GISTs). Its target is a specific oncoprotein produced due to a mutation (the Philadelphia chromosome). Adverse effects include edema, cytopenias, and dyspepsia.
- Gefitinib and Erlotinib. Oral EGFR blockers for lung cancer therapy. May cause rash, diarrhea, and fatal acute respiratory failure.
Clinically important rule: these drugs carry a high risk of drug-drug interactions. For example, grapefruit juice inhibits the CYP3A4 enzyme, which impairs drug degradation in the liver and manifoldly increases their toxicity.