What are the main classifications of anticancer drugs?

Main Classifications of Anticancer Drugs

Anticancer drugs are primarily classified based on their mechanism of action, site of action, and molecular targets, with the main categories being cytotoxic chemotherapy, targeted therapy, immunotherapy, hormone therapy, and biological response modifiers.

1. Cytotoxic Chemotherapy

Cytotoxic agents directly damage DNA or interfere with cell division. These traditional chemotherapeutic agents include:

Alkylating Agents

• Mechanism: Cross-link DNA strands, inhibiting DNA replication and RNA transcription 1
• Examples: Cyclophosphamide, cisplatin, carboplatin

Antimetabolites

• Mechanism: Structural analogs of normal cellular molecules that interfere with DNA/RNA synthesis 1
• Examples: 5-Fluorouracil (5-FU), methotrexate, gemcitabine

Antitumor Antibiotics

• Mechanism: Derived from microorganisms, interfere with DNA function 1
• Examples: Doxorubicin, epirubicin (anthracyclines), mitomycin

Plant Alkaloids

• Mechanism: Bind to tubulin and inhibit microtubule formation, causing metaphase arrest 1
• Examples: Paclitaxel, docetaxel (taxanes), vinorelbine

Topoisomerase Inhibitors

• Mechanism: Interfere with DNA unwinding and replication
• Examples: Irinotecan, topotecan (camptothecins) 1

2. Targeted Therapy

These drugs target specific molecular pathways involved in tumor growth and progression:

Tyrosine Kinase Inhibitors (TKIs)

• Mechanism: Block specific enzymes and growth factor receptors
• Examples: Imatinib, erlotinib, sunitinib 2

HER2-Targeted Agents

• Mechanism: Target HER2 protein overexpressed in some cancers
• Examples: Trastuzumab, pertuzumab, trastuzumab deruxtecan (T-DXd) 3

mTOR Inhibitors

• Mechanism: Block the mTOR pathway involved in cell growth
• Examples: Everolimus, temsirolimus

PARP Inhibitors

• Mechanism: Block DNA repair in cells with BRCA mutations
• Examples: Olaparib, niraparib

3. Immunotherapy

These agents enhance the body's immune response against cancer:

Immune Checkpoint Inhibitors

• Mechanism: Block proteins that prevent T cells from attacking cancer
• Examples: Pembrolizumab, nivolumab (PD-1 inhibitors), atezolizumab, durvalumab (PD-L1 inhibitors) 3, 2

CAR T-Cell Therapy

• Mechanism: Genetically modified T cells to recognize and attack cancer cells 2

4. Hormone Therapy

Used for hormone-dependent cancers:

Selective Estrogen Receptor Modulators (SERMs)

• Mechanism: Block estrogen effects in breast tissue
• Examples: Tamoxifen 2

Aromatase Inhibitors

• Mechanism: Reduce estrogen production
• Examples: Letrozole, anastrozole, exemestane 2

Androgen Deprivation Therapy

• Mechanism: Reduce testosterone levels or block its effects
• Examples: Leuprolide, goserelin 2

5. Biological Response Modifiers

These agents modify the relationship between tumor and host:

Cytokines

• Mechanism: Stimulate immune responses
• Examples: Interferon, interleukin-2

Angiogenesis Inhibitors

• Mechanism: Block formation of new blood vessels
• Examples: Bevacizumab 2

Modern Classification Approaches

Recent classification systems consider multiple dimensions:

1. Site of Action 4, 5:

   • Tumor cell
   • Tumor vasculature
   • Immune system
   • Endocrine system

2. Molecular Target Level 5:

   • DNA-targeting agents
   • RNA-targeting agents
   • Protein-targeting agents

Clinical Considerations

Toxicity Profiles

Different classes have distinct toxicity patterns:

• Myelosuppression: Common with cytotoxic agents like anthracyclines and taxanes 2
• Cardiotoxicity: Associated with anthracyclines and some targeted therapies like trastuzumab 2
• Immune-related adverse events: Unique to immunotherapy 2

Combination Approaches

Modern cancer treatment often involves combining agents from different classes:

• Chemoimmunotherapy: Combining chemotherapy with immune checkpoint inhibitors shows increased efficacy but also increased toxicity in some cancers 2
• Targeted therapy with chemotherapy: HER2-targeted agents with chemotherapy for breast cancer 2

Emerging Trends

The classification of anticancer drugs continues to evolve with:

• Cell biological modifiers: Agents that reverse abnormal biological behavior of tumor cells 6
• Biochemical modulators: Drugs that affect metabolic pathways to enhance chemosensitivity or reduce adverse reactions 6
• Pharmacological effect-based classification: Grouping drugs based on time-dependent versus concentration-dependent effects 7

Understanding these classifications is essential for developing effective treatment strategies and predicting potential toxicities in cancer management.