Mitomycin C is a
mitomycin that is used as a
chemotherapeutic agent by virtue of its antitumour activity.
Medical uses
It is given
intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
ly to treat upper gastro-intestinal cancers (e.g.
esophageal carcinoma),
anal cancers, and
breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
s, as well as by bladder
instillation for superficial
bladder tumours. It is given via intravesical administration for non-muscle invasive bladder cancer.
[ ]
Mitomycin C is also used
topically rather than intravenously for eye surgery. Mitomycin C is applied topically to prevent scarring during glaucoma filtering surgery and to prevent haze after
photorefractive keratectomy
Photorefractive keratectomy (PRK) and laser-assisted sub-epithelial keratectomy (or laser epithelial keratomileusis) (LASEK) are laser eye surgery procedures intended to correct a person's vision, reducing dependency on glasses or contact lenses. ...
(PRK) or
LASIK
LASIK or Lasik (; "laser-assisted in situ keratomileusis"), commonly referred to as laser eye surgery or laser vision correction, is a type of refractive surgery for the correction of myopia, hyperopia, and astigmatism. LASIK surgery is p ...
; mitomycin C has also been shown to reduce fibrosis in
strabismus surgery
Strabismus surgery (also: ''extraocular muscle surgery'', ''eye muscle surgery'', or ''eye alignment surgery'') is surgery on the extraocular muscles to correct strabismus, the misalignment of the human eye, eyes. Strabismus surgery is a one-day ...
.
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.
In June 2025, mitomycin intravesical solution, sold under the brand name Zusduri, was approved in the United States for the treatment of adults with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer.
Contraindications
Pregnant women should not take mitomycin gel because it may cause harm to a developing fetus or newborn baby.
Side effects
It causes delayed
bone marrow
Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
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.
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
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...
were examined.
This treatment resulted in an increase of the
oxidative DNA damage 8-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.
Common side effects are ureteric obstruction (narrowing or blockage of the ureter that may lead to excess fluid in the kidney due to a backup of urine), flank pain (pain occurring on the side of the body), urinary tract infection, hematuria (blood in the urine), renal dysfunction (inability of the kidney to function in its designed capacity), fatigue, nausea, abdominal pain, dysuria (painful or difficult urination) and vomiting.
Pharmacology
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 Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...
of two DNA bases. Both alkylations are sequence specific for a guanine nucleoside in the sequence 5'-CpG-3'.
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.
History
Mitomycin was discovered in 1955 by Japanese scientists in cultures of the microorganism ''
Streptomyces caespitosus''.
[ Mitomycin C was isolated as purple crystals by Wakaki and his coworkers from Kyowa Hakko Kogyo in 1956.]
It was approved based on the results of the OLYMPUS (NCT02793128) multicenter trial involving 71 subjects with low-grade upper urinary tract urothelial cancer (UTUC). These subjects had never undergone treatment (treatment-naïve) or had recurrent low-grade non-invasive UTUC with at least one measurable papillary tumor (a tumor shaped like a small mushroom with its stem attached to the inner lining of an organ) located above the ureteropelvic junction. Subjects received mitomycin gel once a week (mitomycin gel 4 mg per mL instillations via ureteral catheter or nephrostomy tube) for six weeks and, if assessed as a complete response (complete disappearance of the papillary tumor), monthly for up to eleven additional months. Efficacy of mitomycin gel was evaluated using urine cytology (a test to look for abnormal cells in a subjects's urine), ureteroscopy (an examination of the upper urinary tract) and biopsy (if warranted) 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 (58%) 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 (if warranted) every three months for a year following the initiation of therapy. Nineteen subjects (46%) who achieved a complete response continued to have a complete response at the twelve-month mark.
The US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) granted the application for mitomycin gel priority review along with breakthrough therapy, fast track, and orphan drug
An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...
designations. The FDA granted approval of Jelmyto to UroGen Pharma, Inc.
The efficacy of mitomycin C for the treatment of recurrent low-grade intermediate-risk non-muscle invasive bladder cancer was evaluated in ENVISION (NCT05243550), a single-arm, multi-center trial in 240 adults with low-grade non-muscle invasive bladder cancer that recurred after prior transurethral resection of bladder tumor and met 1-2 of the following criteria: multiple tumors, a solitary tumor >3 cm, and/or recurrence within one year. Participants received 75 mg mitomycin intravesical solution instilled once a week for six consecutive weeks. Assessment of tumor status was performed every three months by cystoscopy, for-cause biopsy, and urine cytology.
Research
Potential bis-alkylating heterocyclic quinones were synthesised in order to explore their antitumoral activities by bioreductive alkylation.
In the bacterium ''Legionella pneumophila
''Legionella pneumophila'', the primary causative agent for Legionnaires' disease, Legionnaire's disease, is an Aerobic organism, aerobic, pleomorphic, Flagellum, flagellated, non-spore-forming, Gram-negative bacteria, Gram-negative bacterium. ' ...
'', mitomycin C induces competence
Broad concept article:
*Competence (polyseme), capacity or ability to perform effectively
Competence or competency may also refer to:
*Competence (human resources), ability of a person to do a job properly
**Competence-based management, performa ...
, a condition necessary for the process of natural transformation
In category theory, a branch of mathematics, a natural transformation provides a way of transforming one functor into another while respecting the internal structure (i.e., the composition of morphisms) of the categories involved. Hence, a natur ...
that transfers DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
and promotes recombination between cells. Exposure of the fruitfly ''Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
'' to mitomycin C increases recombination during meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
, a key stage of the sexual cycle. It has been suggested that during sexual process in prokaryote
A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...
s (transformation) and eukaryote
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s (meiosis) DNA cross-links and other damages introduced by mitomycin C may be removed by recombinational repair.
References
External links
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{{Authority control
Antineoplastic drugs
Aziridines
Cancer treatments
Carbamates
Enones
Heterocyclic compounds with 4 rings
Mitomycins
Nitrogen heterocycles
Oncology
Orphan drugs
Quinones
Methoxy compounds