Mitomycin C is a mitomycin that is used as a chemotherapeutic agent by virtue of its antitumour activity. It is given intravenously to treat upper gastro-intestinal cancers, anal cancers, and breast cancers, as well as by bladder instillation for superficial bladder tumours. It causes delayed bone marrow toxicity and therefore it is usually administered at 6-weekly intervals. Prolonged use may result in permanent bone-marrow damage. It may also cause lung fibrosis and renal damage. Mitomycin C has also been used topically rather than intravenously in several areas. The first is cancers, particularly bladder cancers and intraperitoneal tumours. It is now well known that a single instillation of this agent within 6 hours of bladder tumor resection can prevent recurrence. The second is in eye surgery where mitomycin C 0.02% is applied topically to prevent scarring during glaucoma filtering surgery and to prevent haze after PRK or LASIK; mitomycin C has also been shown to reduce fibrosis in strabismus surgery. The third is in esophageal and tracheal stenosis where application of mitomycin C onto the mucosa immediately following dilatation will decrease re-stenosis by decreasing the production of fibroblasts and scar tissue. Mitomycin C is a potent DNA crosslinker. A single crosslink per genome has shown to be effective in killing bacteria. This is accomplished by reductive activation of mitomycin to form a mitosene, which reacts successively via N-alkylation of two DNA bases. Both alkylations are sequence specific for a guanine nucleoside in the sequence 5'-CpG-3'. Potential bis-alkylating heterocylic quinones were synthetised in order to explore their antitumoral activities by bioreductive alkylation. Mitomycin is also used as a chemotherapeutic agent in glaucoma surgery. In the bacterium Legionella pneumophila, mitomycin C induces competence, a condition necessary for the process of natural transformation that transfers DNA and promotes recombination between cells. Exposure of the fruitfly Drosophila melanogaster to mitomycin C increases recombination during meiosis, a key stage of the sexual cycle. It has been suggested that during sexual process in prokaryotes and eukaryotes DNA cross-links and other damages introduced by mitomycin C may be removed by recombinational repair. Anticancer treatments with chemotherapeutic agents often impair brain cell function leading to memory loss and cognitive dysfunction. In order to understand the basis of these impairments, mice were treated with mitomycin C, a chemotherapeutic agent, and cells of the prefrontal cortex were examined. This treatment resulted in an increase of the oxidative DNA damage8-oxo-dG, a decrease in the enzyme OGG1 that ordinarily repairs such damage and epigenetic alterations. These alterations at the DNA level may explain, at least in part, the impairments of cognitive function after chemotherapy. Mitomycin was discovered in the 1950s by Japanese scientists in cultures of the microorganism Streptomyces caespitosus.
Mitomycin gel
In April 2020, mitomycin gel, sold under the brand name Jelmyto, was approved in the United States for the treatment of low-grade upper tract urothelial cancer. Urothelial cancer is a cancer of the lining of the urinary system. Common side effects are ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria and vomiting. Pregnant women should not take mitomycin gel because it may cause harm to a developing fetus or newborn baby. Mitomycin gel is an alkylating drug, meaning it inhibits the transcription of DNA into RNA, stopping protein synthesis and taking away the cancer cell's ability to multiply. It was approved based on the results of the OLYMPUS multicenter trial involving 71 subjects with low-grade UTUC. These subjects had never undergone treatment or had recurrent low-grade non-invasive UTUC with at least one measurable papillary tumor located above the ureteropelvic junction. Subjects received mitomycin gel once a week for six weeks and, if assessed as a complete response, monthly for up to eleven additional months. Efficacy of mitomycin gel was evaluated using urine cytology, ureteroscopy and biopsy three months following the initiation of therapy. The primary endpoint was complete response at three months following initiation of therapy. A complete response was found in 41 of the 71 subjects following six treatments of mitomycin gel administered weekly. Durability of the effect of mitomycin gel in subjects with a complete response was also evaluated using urine cytology, ureteroscopy and biopsy every three months for a year following the initiation of therapy. Nineteen subjects who achieved a complete response continued to have a complete response at the twelve-month mark. The US Food and Drug Administration granted the application for mitomycin gel priority review along with breakthrough therapy, fast track, and orphan drug designations. The FDA granted approval of Jelmyto to UroGen Pharma, Inc.
