Mitomycin C is a specialized medication used in the treatment of various cancers. It belongs to a class of drugs known as antineoplastic antibiotics, initially isolated from the bacterium Streptomyces caespitosus in the 1950s. This compound functions by interfering with the cellular processes characteristic of rapidly growing cells, making it a tool in oncology.
The Activation of Mitomycin C
Mitomycin C is a prodrug, meaning it is initially inactive and requires a chemical transformation within the body to become effective. This activation involves a reduction reaction facilitated by enzymes inside cells. Intracellular flavin reductases, which utilize molecules like NADH or NADPH as electron donors, play a role in this conversion.
Numerous enzymes can catalyze this bioreduction, leading to the drug’s active form. One enzyme, DT-diaphorase (NQO1), is often present in higher amounts within cancer cells. This activation transforms Mitomycin C into a reactive intermediate, typically a mitosene, which then exerts its therapeutic effects. The presence of a thiolytic environment, often found within tumor tissues, also contributes to the drug’s activation and release.
Mitomycin C’s DNA Targeting Action
Once activated, Mitomycin C primarily targets DNA within cells. It functions as an alkylating agent, forming covalent bonds with DNA. This binding leads to the formation of “cross-links” between the strands of the DNA double helix.
These cross-links can occur within a single DNA strand (intrastrand) or between the two complementary strands (interstrand). Interstrand cross-links are disruptive, preventing DNA strands from separating. This inhibition interferes with essential cellular processes like DNA replication (where strands unwind to be copied) and transcription (where genetic information is read from DNA to synthesize RNA). This disruption of DNA synthesis occurs primarily during the late G1 and S phases of the cell cycle. The inability of cells to accurately replicate DNA or transcribe genes ultimately leads to cell death, making activated Mitomycin C effective against rapidly dividing cells, like cancer cells.
Therapeutic Uses and Side Effects from DNA Damage
Mitomycin C’s mechanism of action, involving DNA damage and inhibited cell division, underpins its therapeutic uses and side effects. Its ability to impact rapidly dividing cells makes it valuable for treating several solid tumors. It is used in cancers of the stomach, pancreas, anal region, breast, and esophagus. The drug is also administered directly into the bladder for superficial bladder tumors and for low-grade upper urinary tract urothelial cancer.
While Mitomycin C targets fast-growing cancer cells, it also affects healthy cells that divide quickly. This non-specific action leads to common side effects. Bone marrow suppression is common, leading to reduced white blood cells (increasing infection risk) and decreased platelets (increasing bruising and bleeding). A reduction in red blood cells, resulting in anemia, is also possible.
Other common adverse effects include nausea, vomiting, and diarrhea. Hair loss is also a common side effect. Less common but serious complications include lung fibrosis, kidney damage, and hemolytic uremic syndrome. These side effects underscore the balance clinicians must strike when using such potent medications.