General Overview and Main Classes
These medicinal products are produced by soil fungi of the genus Streptomyces. In modern clinical practice, they are divided into several key groups:
- Anthracyclines (including doxorubicin and daunorubicin);
- Bleomycin — a glycopeptide complex;
- Mitomycin;
- Dactinomycin (actinomycin D) — historically the first antibiotic introduced into the arsenal of antitumor chemotherapy.
Most drugs in this category are administered exclusively parenterally (most commonly intravenously) because they are degraded by digestive enzymes or are not absorbed properly in the gastrointestinal tract. An important general pharmacokinetic feature is their inability to cross the blood-brain barrier.
Dactinomycin: Mechanism and Features
Dactinomycin is used for such pathologies as Wilms tumor, choriocarcinoma, and rhabdomyosarcoma.
Mechanism of Action:
- Intercalation: The molecule inserts into the DNA helix strictly between guanine-cytosine base pairs, forming a stable complex.
- Suppression of RNA synthesis: The drug inhibits DNA-dependent RNA polymerase, halting transcription.
- Free radicals: During degradation, free radicals can be released, damaging the structure of nucleic acids.
The drug is eliminated via the gastrointestinal tract with bile. Key risks include immunosuppression, myelosuppression, and severe local toxicity: extravasation of the solution causes severe tissue necrosis.
Anthracycline Antibiotics: Doxorubicin and Daunorubicin
Anthracyclines are structurally related compounds, where doxorubicin is a hydroxylated analogue of daunorubicin. They exhibit four mechanisms of cytotoxic action: DNA intercalation, inhibition of the vital enzyme topoisomerase II, membrane toxicity, and induction of oxidative stress.
- Indications: Doxorubicin is prescribed for a wide range of solid tumors (sarcomas, breast cancer) and hematologic malignancies. Daunorubicin is used primarily for acute leukemias.
- Side Effects: The dose-limiting factor is myelosuppression. The most dangerous complication is cardiotoxicity due to lipid peroxidation in the myocardium. Dexrazoxane and liposomal formulations are used for prevention. A characteristic visual sign of administration is the reddish discoloration of urine and bodily fluids.
Bleomycin: Phase Specificity and Organotropism
Bleomycin is a mixture of glycopeptides that acts in a phase-specific manner, arresting cells primarily in the G2 phase of the cell cycle.
The drug interacts with ferrous iron ($Fe^{2+}$) and DNA to form a ternary complex that generates reactive oxygen species and causes DNA strand breaks.
- Organotropism: In the liver and spleen, the drug is rapidly degraded by the enzyme hydrolase, but in the skin and lungs, the activity of this enzyme is low. Consequently, high concentrations of the active substance accumulate in lung tissue, which can lead to severe and potentially fatal pulmonary fibrosis ("bleomycin lung").
- Distinctive Feature: Unlike most other cytostatics, bleomycin does not cause bone marrow suppression.