Enzyme Preparations: L-Asparaginase
The active substance is an enzyme derived from the metabolic activity of Escherichia coli or Erwinia chrysanthemi bacteria.
Mechanism of Action is based on the principle of "metabolic starvation." Unlike healthy cells, malignant cells are unable to independently synthesize the amino acid asparagine and are entirely dependent on its supply from the bloodstream. The drug deaminates circulating asparagine, cleaving it into aspartic acid and ammonia. The tumor experiences an acute shortage of building blocks, causing rapidly proliferating cells to die.
Clinical Features:
- Indications: Acute lymphoblastic leukemia (often combined with prednisone or vincristine).
- Administration: Exclusively parenteral, as the protein molecule of the enzyme is completely destroyed in the gastrointestinal tract.
- Adverse Effects:
- Allergic reactions to the foreign bacterial protein.
- Neurotoxicity (seizure, coma) due to ammonia poisoning, a byproduct of cleavage.
- Reduced blood clotting resulting from the suppression of hepatic protein synthesis.
- Internal organ damage (pancreatitis, liver dysfunction).
Topoisomerase I Inhibitors
This group includes irinotecan and topotecan. These are semisynthetic derivatives of the alkaloid camptothecin, which was originally isolated from Camptotheca acuminata. A complex lactone ring is responsible for the pharmacological activity of the molecule.
These drugs are phase-specific and act strictly during the S phase of the cell cycle. They selectively block the enzyme topoisomerase I, leading to critical disruption of DNA repair processes and arrest of cell division.
They are administered intravenously as infusions. The primary hazard during therapy is pronounced hematotoxicity, manifested as neutropenia, anemia, and thrombocytopenia. Systemic reactions such as alopecia, nausea, vomiting, and diarrhea are also possible.
Topoisomerase II Inhibitors
This group is represented by etoposide and teniposide, which are semisynthetic derivatives of podophyllotoxin. The parent alkaloid is extracted from the Mayapple plant (Podophyllum peltatum).
Mechanism of Action: The drug molecule binds simultaneously to the DNA strand and the topoisomerase II enzyme, forming a stable ternary complex. This blocks normal enzyme function, triggers DNA strand breaks, and leads to subsequent cell death.
Indications and Routes of Administration:
- Etoposide: Used for small cell lung cancer (oat cell carcinoma, prone to rapid and aggressive metastasis) and testicular carcinoma (as part of combination therapy with cisplatin and bleomycin). The drug can be administered parenterally and taken orally.
- Teniposide: Indicated for acute leukemias and solid tumors of the central nervous system (neuroblastomas, gliomas). Administered exclusively intravenously.
Among the adverse effects of this entire group, myelosuppression (severe bone marrow suppression), dyspeptic disorders, immune-mediated allergic reactions, and dermatological problems (alopecia) predominate.
Arsenic Compounds
In modern oncology, arsenic trioxide is used. Historically, arsenic compounds were widely used in traditional Chinese medicine to treat psoriasis and syphilis, but were later successfully repurposed to combat malignant neoplasms.
Administered intravenously in the treatment of leukemias, the drug induces the degradation of a specific leukemic oncoprotein (PML/RAR-$\alpha$) and triggers the mitochondrial apoptotic pathway through the activation of intracellular enzymes—caspases.
Due to its high toxicity, arsenic trioxide is used with great caution. Major adverse reactions include:
- Cardiotoxicity: Severe arrhythmias, pathological QT interval prolongation, and ECG changes.
- Systemic Manifestations: Marked fluid retention, dyspnea, fever.
- Dermatological Reactions: Various types of rashes.