Anticancer Drug Classes: Mechanisms, Side Effects, Indications

Anticancer drugs (also called antineoplastic agents) are medications that treat malignant (cancerous) disease1. They act by killing tumor cells or inhibiting their proliferation. Since cancer involves cells growing and dividing without control, these drugs typically target rapidly dividing cells.

In practice, most anticancer drugs damage DNA or disrupt cell division, which prevents cancer cells from replicating2. A consequence of this mechanism is that normal fast-dividing tissues (blood-forming cells, hair follicles, gut lining, etc.) are often affected, leading to common side effects (bone marrow suppression, hair loss, mucositis, etc.)3

Pharmacologically, anticancer agents are classified by their mechanism of action4. Major categories include:

• Alkylating agents (e.g. cyclophosphamide, cisplatin): These drugs form cross-links in DNA strands, blocking replication and triggering cell death.

• Antimetabolites (e.g. methotrexate, 5-fluorouracil): These mimic natural metabolites (nucleotides) and get incorporated into DNA/RNA, or inhibit enzymes, disrupting DNA/RNA synthesis.

• Natural product (plant-derived/bacterial) agents:

  • Mitotic inhibitors (e.g. vincristine, paclitaxel) – often derived from plants – which bind to microtubules and prevent mitosis.

  • Antitumor antibiotics (e.g. doxorubicin, bleomycin) – bacterial products that intercalate DNA or generate free radicals to damage DNA.

• Hormonal therapies (e.g. tamoxifen, aromatase inhibitors, androgen blockers): These drugs block or modulate hormones (estrogens, androgens) that certain cancers (like breast or prostate cancer) depend on for growth5.

• Targeted therapies: Agents such as tyrosine kinase inhibitors (e.g. imatinib) and monoclonal antibodies (e.g. trastuzumab) that specifically block molecular signals or receptors critical for cancer cell survival6.

• Immunotherapeutic agents: Biologic drugs (e.g. immune checkpoint inhibitors, IL-2) that enhance the immune system’s ability to recognize and kill cancer cells.

Clinically, anticancer drugs are chosen based on cancer type, stage, and patient factors7. They are often given in combination regimens (to attack cancer on multiple fronts) and in cycles (periods of treatment followed by rest).

Most are administered intravenously, though some are oral or injectable8. Treatment intent may be curative (eliminate the cancer), adjuvant/neoadjuvant (before or after surgery/radiation to shrink or eradicate residual disease), or palliative (control symptoms and slow progression).

In all cases, the goal is to exploit the drug’s mechanism to reduce tumor cells. As one source notes, chemotherapy (a major subset of anticancer drugs) uses chemical agents to destroy cancer cells9, illustrating the principle common to this class of drugs.

Alkylating Agents

• Mechanism: Electrophilic agents that cross‑link DNA (especially guanine N7), preventing DNA replication (cell-cycle non‑specific)10. Many are prodrugs.

• Key Drugs and Actions: Cyclophosphamide (nitrogen mustard) – activated in liver, forms DNA crosslinks11; Cisplatin (a platinum analog) – forms intra‑ and inter‑strand DNA crosslinks.

• Side Effects: Myelosuppression (especially leukopenia), cyclophosphamide causes hemorrhagic cystitis (acrolein metabolite)12, alopecia, nausea/vomiting. Cisplatin is notably nephrotoxic (needs hydration) and ototoxic, with less bone marrow suppression.

• Indications: Broad-spectrum use. Cyclophosphamide – lymphomas, leukemias, breast cancer, ovarian cancerncbi.nlm.nih.gov. Cisplatin – testicular, ovarian, bladder and lung cancers.

Antimetabolites Anticancer Drugs

• Mechanism: Nucleoside or folate analogs that inhibit DNA/RNA synthesis (S‑phase specific).

• Key Drugs: Methotrexate (folate analog inhibiting dihydrofolate reductase), 5‑Fluorouracil (pyrimidine analog blocking thymidylate synthase), 6‑Mercaptopurine (purine analog inhibiting purine synthesis)13, Cytarabine (pyrimidine analog incorporated into DNA).

• Side Effects: Myelosuppression (dose-limiting), mucositis, diarrhea. Methotrexate also causes hepatotoxicity and mucositis; 5‑FU causes hand–foot syndrome and photosensitivity; 6‑MP causes hepatotoxicity and requires TPMT monitoring14. All can cause pancytopenia.

• Indications: ALL (methotrexate, 6‑MP), solid tumors (5‑FU for colon, breast), AML (cytarabine), and others. For example, 6‑MP is used in maintenance of ALL15; methotrexate in choriocarcinoma and rheumatoid arthritis (lower dose).

Plant Alkaloids & Topoisomerase Inhibitors Anticancer Drugs

• Vinca Alkaloids: Inhibit microtubule polymerization (M‑phase arrest). Vincristine – neurotoxic (peripheral neuropathy, constipation)16, little myelosuppression; Vinblastine – more marrow suppression, less neuropathy.
• Side Effects: Neuropathy, ileus, SIADH (vincristine), myelosuppression (vinblastine), alopecia.
• Indications: Vincristine – ALL, lymphomas (e.g. Hodgkin’s in ABVD regimen), Wilms tumor. Vinblastine – Hodgkin’s lymphoma (ABVD), testicular cancer, Kaposi sarcoma.

 

• Taxanes: Stabilize microtubules (prevent depolymerization). Paclitaxel – binds β‑tubulin and freezes microtubules17.

• Side Effects: Peripheral neuropathy, myelosuppression, hypersensitivity reactions (require premedication)18, alopecia.

• Indications: Breast, ovarian, lung cancers; Kaposi sarcoma. (E.g., paclitaxel used in breast/ovarian carcinomas.)

• Topoisomerase Inhibitors: Topo I inhibitors (irinotecan, topotecan) – prevent DNA unwinding, cause single‑strand breaks. Irinotecan causes severe diarrhea and myelosuppression. Topo II inhibitors (etoposide, teniposide) – cause double‑strand DNA breaks.

• Side Effects: Myelosuppression, alopecia, mucositis. Etoposide causes neutropenia, hypotension (IV).

• Indications: Etoposide – small cell lung cancer, testicular cancer19; Topo I inhibitors – colon (irinotecan) and ovarian (topotecan) cancers.

Antibiotic (Anthracycline) Anticancer Agents

• Mechanism: DNA intercalation, Topoisomerase II inhibition, and free radical generation20. (Bind DNA and stabilize strand breaks.)

• Key Drugs: Doxorubicin – an anthracycline (“red devil”).

• Side Effects: Severe myelosuppression, alopecia, mucositis; cardiotoxicity (dose-dependent dilated cardiomyopathy, arrhythmias)21. Doxorubicin can also cause tissue necrosis if extravasated.

• Indications: Many cancers: leukemias/lymphomas, breast cancer, sarcomas, bladder, lung, thyroid22. (Liposomal doxorubicin used in Kaposi’s sarcoma, recurrent ovarian cancer.)

Hormonal Agents Anticancer Drugs

• Mechanism: Modulate hormone signaling in hormone-dependent tumors. Tamoxifen – selective estrogen receptor modulator (SERM) that blocks estrogen receptors in breast23. Aromatase inhibitors (anastrozole, letrozole) – block estrogen synthesis (postmenopausal ER+ breast cancer). Antiandrogens (flutamide, bicalutamide) – block androgen receptors. GnRH analogs (leuprolide) – initially stimulate then suppress LH/FSH (prostate cancer).

• Side Effects: Tamoxifen – hot flashes, thromboembolism, endometrial hyperplasia/cancer24. Aromatase inhibitors – osteoporosis, arthralgias, hot flashes. Antiandrogens/GnRH agonists – gynecomastia, sexual dysfunction, osteoporosis.

• Indications: Tamoxifen – ER+ breast cancer (adjuvant and metastatic)25. Aromatase inhibitors – ER+ breast cancer (postmenopausal). GnRH analogs and antiandrogens – prostate cancer; tamoxifen also used in infertility (ovulation induction) and gynecomastia.

Targeted Therapies (Tyrosine Kinase Inhibitors)

• Mechanism: Small molecules that inhibit specific oncogenic kinases. Imatinib – inhibits BCR‑ABL tyrosine kinase (and c-KIT, PDGF receptors)26. Others include EGFR inhibitors (erlotinib), VEGF receptor inhibitors (sunitinib), etc.

• Side Effects: Imatinib – fluid retention (periorbital edema), nausea, diarrhea, muscle cramps, rash, myelosuppression27 Other TKIs have class effects: rash (EGFR inhibitors), hypertension (VEGF inhibitors), hand–foot syndrome (sorafenib), hyperglycemia (nilotinib), etc.

• Indications: Imatinib – chronic myelogenous leukemia (CML, Philadelphia chromosome), gastrointestinal stromal tumor (c-KIT+ GIST)28. Erlotinib – lung cancer (EGFR-mutant). Others: trastuzumab (HER2 inhibitor) in breast, though it’s a monoclonal (see below).

Immunotherapies (Checkpoint Inhibitors)

• Mechanism: Monoclonal antibodies that block immune “checkpoints” (inhibitory receptors) on T cells, restoring anti-tumor immunity29. PD-1 inhibitors (pembrolizumab, nivolumab) prevent PD-1/PD-L1 interaction; CTLA-4 inhibitors (ipilimumab) block CTLA-4.

• Side Effects: Immune-related adverse events – any organ can be attacked. Common: fatigue, rash, pruritus, diarrhea (colitis)30. Serious: autoimmune colitis, pneumonitis, hepatitis, endocrinopathies (hypophysitis, thyroiditis)31. Infusion reactions can occur.

• Indications: Various cancers (often advanced/metastatic): melanoma, non-small cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head/neck cancers, urothelial cancer, MSI-high tumors, etc. Pembrolizumab is approved for melanoma, NSCLC, head/neck, Hodgkin’s, and others.

Monoclonal Antibodies (Targeted mAbs)

• Mechanism: Antibodies against tumor antigens or signaling molecules. For example, Rituximab targets CD20 on B cells (causing ADCC and complement lysis); Trastuzumab targets HER2/neu; Bevacizumab targets VEGF.

• Side Effects: Infusion reactions (fever, chills, hypotension), risk of infections (due to cell depletion). Rituximab can cause reactivation of HBV, tumor lysis syndrome. Trastuzumab causes cardiomyopathy; bevacizumab causes hypertension, bleeding, and thrombosis. Skin rash is common with EGFR-directed mAbs (e.g., cetuximab).

• Indications: Rituximab – B-cell lymphomas, CLL; also rheumatoid arthritis. Trastuzumab – HER2+ breast and gastric cancer. Bevacizumab – colorectal, lung, renal, glioblastoma. Cetuximab – colorectal (KRAS WT), head/neck cancers.

Summary Table of Anticancer Drugs (Comparison of Key Agents)

Key: Each class of anticancer drugs has a distinct mechanism. For example, alkylating agents crosslink DNA to block replication32, while antimetabolites mimic nucleotides to inhibit DNA synthesis.

Plant alkaloids disrupt the microtubule spindle (vincas vs. taxanes have opposite actions on microtubules), and antibiotics like doxorubicin intercalate DNA and generate free radicals33.

Hormonal therapies alter growth signaling (e.g. tamoxifen blocks estrogen receptors34). Targeted agents inhibit specific oncogenic kinases (e.g. imatinib inhibits BCR-ABL35). Immunotherapies (checkpoint inhibitors) remove inhibitory signals on T-cells36, leading to immune-mediated tumor attack.

Monoclonal antibodies target specific cell-surface antigens or receptors to kill cancer cells or block growth signals. Side effects often reflect a drug’s mechanism: eg, doxorubicin’s free radicals cause cardiotoxicity37; vinca alkaloids’ microtubule inhibition causes neuropathy38.

Indications vary by drug and target; e.g., cisplatin is key for testicular and ovarian cancer, methotrexate for leukemias/lymphomas, trastuzumab for HER2+ breast cancer, pembrolizumab for melanoma and other PD-L1–expressing tumors. The table above provides a concise comparison of agents, mechanisms, toxicities, and uses.