Classification of Anticancer Drugs and Inclusion of Newly Approved Agents
Anticancer drugs are classified based on two primary organizational frameworks: their site of action (tumor cell, vasculature, immune system, or endocrine system) and their mechanism of action (molecular target), and newly approved drugs are systematically incorporated into this classification system as they receive regulatory approval. 1
Rationale Behind Classification Systems
Historical Evolution of Classification
Traditional classification systems organized anticancer drugs by either their mechanism of action or their origins, grouping them into categories such as alkylating agents, antimetabolites, antitumor antibiotics, and plant alkaloids 2
This older system became inadequate with the arrival of numerous new agents with novel mechanisms of action that did not fit neatly into classical categories of chemotherapy, hormones, tyrosine-kinase inhibitors, and monoclonal antibodies 1, 3
Modern Two-Level Classification Framework
The current classification system operates on two hierarchical levels to accommodate the expanding therapeutic arsenal: 1
Level 1: Site of Action
- Tumor cell-directed agents: Act directly on cancer cells through DNA, RNA, or protein targets 3
- Vascular-directed agents: Target tumor endothelium and extracellular matrix 3
- Immune system modulators: Regulate host immune response against tumors 4
- Endocrine system agents: Affect hormonal pathways driving tumor growth 1
Level 2: Mechanism of Action
Refers to the specific molecular target of the drug, such as EGFR, PDGFR, VEGFR, cyclin-dependent kinases, or topoisomerases 5, 2
This molecular target-based approach allows for precise categorization of agents like tyrosine kinase inhibitors, monoclonal antibodies, and signal transduction inhibitors 5
Alternative Cell Biological Classification
Some systems divide drugs into cytotoxic drugs (direct tumor cell killers) and modifiers (regulators of tumor-host-drug interactions) 4
Modifiers are further subdivided into: cell biological modifiers (reverse abnormal tumor behavior), biological response modifiers (regulate host response), and biochemical modulators (affect drug metabolism to enhance efficacy or reduce toxicity) 4
Inclusion of Newly Approved Drugs
Systematic Integration Process
When a drug receives FDA or EMA approval, it is immediately incorporated into the existing classification framework based on its documented site and mechanism of action. 1
The classification system is designed to be dynamic and expandable, accommodating new agents as they emerge from clinical development 1
More than 300 biological molecular targets have been identified to date, providing a comprehensive framework for classifying novel agents 5
Practical Application in Clinical Guidelines
National guidelines (NCCN, ASCO) incorporate newly approved agents into treatment algorithms based on their classification and clinical trial evidence 6
For example, when vemurafenib was approved for BRAF V600 mutation-positive melanoma, it was immediately classified as a targeted agent (site: tumor cell; mechanism: BRAF kinase inhibitor) and incorporated into treatment recommendations 6
Similarly, bevacizumab was classified as an anti-angiogenic agent (site: tumor vasculature; mechanism: VEGF inhibitor) and integrated into combination regimens for multiple tumor types 6
Clinical Implementation Considerations
The selection, dosing, and administration of anticancer agents require healthcare teams experienced in their use, as modifications are often necessary based on toxicities, patient variability, and comorbidities 6
Combination regimens must account for the classification of each component agent, as drugs with different sites and mechanisms of action may provide synergistic benefit or require specific sequencing to avoid antagonism 6
Phase I combination trials require explicit hypotheses justifying the combination based on pharmacological or biological rationale, supported by preclinical or clinical data 6
Common Pitfalls in Classification
Avoid rigid adherence to outdated classification schemes that group drugs solely by chemical structure or origin, as this fails to capture the therapeutic relevance of modern targeted agents 1, 3
Do not assume all drugs within a class have identical properties: even drugs targeting the same molecular pathway may have different toxicity profiles, pharmacokinetics, and clinical applications requiring individualized classification 6, 5
Recognize that some agents have multiple mechanisms of action and may appropriately fit into more than one classification category, requiring context-specific categorization based on their primary therapeutic use 4