Antineoplastic agents

Classification by cell cycle relationship

The cell life cycle often serves as the basis for therapy selection. Drugs are divided into two large groups depending on when they exhibit activity:

• Phase-specific agents. Strike the cell at a strictly defined moment in its development. Most effective against tumors with a high proportion of actively dividing cells. For example, in the S phase (during DNA replication), antimetabolites and etoposide work. In the M phase (mitosis proper), taxanes, vinca alkaloids, and bleomycin act.
• Phase-non-specific agents. Damage cells regardless of the cycle stage, reaching them even in the resting phase ($G_0$). This group includes alkylating agents (damaging DNA by attaching alkyl groups), anthracyclines, platinum-based drugs, and antineoplastic antibiotics of microbial origin.

Hormone therapy

Some types of tumors are hormone-dependent—their growth is stimulated by the body's natural hormones. Pharmacological intervention in such cases comes down to using antagonists:

1. Prostate gland. Tissue is stimulated by testosterone and adrenal androgens. Antiandrogens (e.g., flutamide) are used for treatment, which block receptors in the target tissue.
2. Breast. Tumor growth is stimulated by estrogens. Tamoxifen, which blocks estrogen receptors directly in the breast tissue, is used as an antiestrogen.

Principles of combination chemotherapy

Using a single drug rarely yields a sustained result, so physicians use combinations. This allows solving three tasks: covering a heterogeneous tumor cell population, slowing down the development of resistance, and striking a balance between efficacy and toxicity.

The main principle of selecting combinations is toxicological. The regimen includes drugs that are effective on their own but possess different specific organ toxicities. As a result, their therapeutic effect on the tumor is summed up, while side effects on healthy organs do not overlap.

Resistance and side effects

Tumor resistance to treatment can be primary (typical for solid tumors such as melanoma) and secondary. Secondary resistance is often associated with a mutation in the TP53 gene (found in 50% of cancer cases), causing damaged cells to evade destruction. Another mechanism is the action of transport proteins such as P-glycoprotein (MDR1). It acts as a membrane pump, actively pumping the drug out of the cytoplasm.

Since cytostatics act indiscriminately, all rapidly renewing tissues suffer: bone marrow, mucosal epithelium, hair follicles. This causes nausea, myelosuppression, and alopecia (the latter is reversible). In addition, specific organ toxicity is distinguished, which is often irreversible:

• Cyclophosphamide damages the urinary bladder.
• Doxorubicin is cardiotoxic.
• Bleomycin causes pulmonary fibrosis.

Class and exam questions

What else to study on this topic

• Mechanisms of action of antimetabolites (folic acid, purine, and pyrimidine analogues)
• Detailed classification of alkylating agents and platinum compounds
• The role of the TP53 tumor suppressor gene in the development of secondary drug resistance
• The "Other drugs" group: enzymes, targeted agents, and topoisomerase inhibitors
• General classification: cytotoxic agents, hormones, and monoclonal antibodies

Other topics in the "Antineoplastic agents" section

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