Antitumor Antibiotics

Antitumor antibiotics, also known as antineoplastic antibiotics, are the product of soil microbes, Streptomyces bacteria. The commonly used types of antitumor antibiotics—bleomycin, dactinomycin, and anthracyclines—have a wide spectrum of activity against hematologic malignancies and solid tumors. Bleomycin differs from the rest of the drugs owing to its cell cycle–specific action during the G2 phase. Mechanisms of actions of these drugs include free radical damage to DNA, topoisomerase II inhibition, binding of DNA via intercalation, and alteration of cell membrane fluidity and transport of ions. Important adverse effects include cardiotoxicity (acute and chronic) and myelosuppression.

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Antitumor antibiotics, agents isolated from strains of Streptomyces, are used for cancer treatment owing to their ability to interfere with DNA and/or RNA synthesis, thus leading to cancer cell death. The effects of these drugs are too toxic for use in bacterial infections.

Agents within this class include:

  • Cell cycle–specific: bleomycin
  • Cell cycle–nonspecific:
    • Dactinomycin
    • Mitomycin
    • Anthracyclines



  • Cell cycle–specific drug that acts on the G2 phase of the cell cycle
  • Mechanism of action: 
    • Contains a DNA-binding site and an iron-binding site → binds DNA, forming a complex (DNA–bleomycin–Fe(II)) 
    • Effect: DNA double- and single-stranded breaks
  • Pharmacokinetics:
    • IV, IM, SC, intrapleural
    • Metabolism: inactivated enzymatically by bleomycin hydrolase (not found in significant amounts in skin and lungs)
    • Half-life: 2 hours (IV)
    • Excretion: renal 
  • Indications (labeled): 
    • Hodgkin lymphoma
    • Head and neck cancer
    • Testicular cancer
    • Malignant pleural effusion (sclerosing agent)
Structure of bleomycin

Structure of bleomycin

Image: “Bleomycin A2” by Yikrazuul. License: Public Domain

Adverse effects

  • Pulmonary toxicity presenting as pneumonitis:
    • Most severe toxicity
    • May lead to pulmonary fibrosis
  • Hepatotoxicity
  • Renal toxicity
  • Idiosyncratic reaction (↓ blood pressure, wheezing, fever, chills)
  • Dermatologic: 
    • Rash
    • Hyperpigmentation
    • Alopecia

Contraindications and drug interactions

  • Contraindications: 
    • Hypersensitivity to the drug
    • Pregnancy (1st trimester)
  • If there are pulmonary changes, treatment should be withheld and relation to bleomycin should be investigated.
  • Dose adjustment in impaired renal function
  • Drug interactions (↑ pulmonary toxicity of bleomycin):
    • Brentuximab
    • Gemcitabine
    • Granulocyte colony-stimulating factors
    • Oxygen



  • Dactinomycin (actinomycin D)
  • Chromopeptide from Streptomyces
  • Mechanism of action: 
    • Forms a bond with DNA, intercalating between base pairs (cytosine and guanine)
    • Prevents the activity of RNA polymerase, blocking transcription of DNA
    • Also produces single-stranded breaks in DNA
  • Pharmacokinetics:
    • IV
    • Does not cross blood–brain barrier
    • Minimal metabolism
    • Half-life: 36 hours
    • Excretion: urine and feces, 30%
  • Indications (labeled):
    • Solid tumors
    • Wilms tumor
    • Ewing sarcoma
    • Gestational trophoblastic neoplasia
    • Rhabdomyosarcoma
Structure of dactinomycin

Structure of dactinomycin

Image: “Actinomycin D” by Edgar181. License: Public Domain

Adverse effects

  • Myelosuppression
  • Mucocutaneous toxicity (such as Stevens-Johnson syndrome, toxic epidural necrolysis)
  • Hepatotoxicity (such as ↑ bilirubin, liver enzymes)
  • Nephrotoxicity
  • GI toxicity: nausea, vomiting, diarrhea
  • Extravasation (causes local tissue damage)
  • Secondary malignancy (such as leukemia)

Contraindications and drug interactions

  • Avoid live vaccines before and during dactinomycin treatment.
  • Dactinomycin:
    • ↑ Toxicity when combined with radiation therapy
    • ↓ Effects of inactivated and live vaccines
    • ↑ Toxic effects of live vaccines



  • Mitomycin: isolated from Streptomyces caespitosus
  • Mitomycin is activated into mitosene.
  • Mechanism of action:
    • Mitosene alkylates DNA cross links DNA
    • Prevents DNA and RNA synthesis
  • Pharmacokinetics:
    • Metabolism: liver
    • Half-life: < 1 hour
    • Excretion: mainly in feces (some through renal excretion)
  • Indications:
    • Gastric cancer
    • Pancreatic cancer
    • Off-label: anal cancer, bladder cancer, esophageal cancer, cervical cancer, vulvar cancer
Structure of mitomycin

Structure of mitomycin

Image: “Mitomycin” by Fvasconcellos. License: Public Domain

Adverse effects

  • Myelosuppression
  • Myocardial toxicity (heart failure)
  • Hemolytic uremic syndrome and renal failure
  • Bladder fibrosis (with intravesical administration)
  • Pulmonary toxicity
  • GI toxicity: nausea, vomiting, mucositis
  • Extravasation

Contraindications and drug interactions

  • Contraindications:
    • Hypersensitivity
    • Bleeding tendency
    • Discontinue medication with significant organ toxicity
  • Drug interactions:
    • Concurrent vinca alkaloid treatment can cause bronchospasm.
    • ↓ Effects of inactivated and live vaccines
    • ↑ Toxic effects of live vaccines



  • Anthracyclines or anthracycline antibiotics are derived from Streptomyces peucetius var. caesius.
  • Chemotherapy agents frequently used for different types of cancers (hematologic cancers and solid tumors)
  • Mechanisms of action:
    • Inhibit topoisomerase II and impede DNA repair
    • Form oxygen free radicals, which bind to single- and double-stranded DNA → cause damage
    • Intercalate with DNA to block transcription and replication
    • Bind to cellular membranes and alter ion transport
  • Pharmacokinetics:
    • IV
    • Metabolism: liver via hydrolysis of the anthracycline ring
    • Elimination: mostly in feces through biliary excretion
  • Indications:
    • Doxorubicin:
      • Breast cancer
      • Ovarian cancer 
      • ALL, AML
      • Hodgkin lymphoma, non-Hodgkin lymphoma
      • Bladder cancer
      • Bone sarcoma, soft tissue sarcoma
      • Bronchogenic carcinoma
      • Gastric cancer
      • Neuroblastoma
      • Thyroid carcinoma
      • Wilms tumor
    • Daunorubicin:
      • ALL
      • AML
    • Idarubicin: AML
    • Epirubicin: breast cancer
    • Mitoxantrone:
      • Advanced prostate cancer 
      • AML
      • Multiple sclerosis
Structure of doxorubicin

Structure of doxorubicin

Image: “Doxorubicin2” by NEUROtiker. License: Public Domain

Adverse effects

  • Cardiotoxicity:
    • Acute: ECG disturbances, pericarditis, myocarditis, elevated troponin level
    • Chronic: 
      • Dilated cardiomyopathy (dose-dependent) leading to congestive heart failure
      • Results from free oxygen radicals damaging the myocardium
      • Dexrazoxane: given to prevent anthracycline-induced cardiotoxicity (metastatic breast cancer) 
    • Liposomal formulations of anthracyclines have reduced incidence of cardiotoxicity.
  • Myelosuppression
  • Secondary malignancy
  • Hepatic impairment
  • Extravasation
  • Radiation recall: Erythema and skin desquamation can develop in areas treated with radiation. 
  • Tumor lysis syndrome
  • Mucositis

Contraindications and drug interactions

  • Contraindications:
    • Hypersensitivity to the medication
    • Impaired cardiac function or severe cardiac disease or arrhythmia
    • Impaired liver function
    • Severe myelosuppression
    • Active infection 
  • Drug interactions (particularly doxorubicin):
    • The following ↑ risk of cardiotoxicity:
      • Trastuzumab
      • Taxanes
      • Cyclophosphamide
    • ↓ Effects of inactivated and live vaccines
    • ↑ Toxic effects of live vaccines

Comparison with other chemotherapeutic agents

Various chemotherapy drugs and their effects on the cell cycle

Various chemotherapy drugs and their effects on the cell cycle

Image by Lecturio.
Table: Comparison of the cell cycle–independent chemotherapy drugs
Drug classMechanism
Antitumor antibiotics:
  • Dactinomycin
  • Mitomycin
Intercalate between bases, leading to blockage of DNA or RNA synthesis and prevention of DNA replication
  • Inhibition of topoisomerase II
  • DNA intercalation, leading to DNA and RNA inhibition
  • Promote reactive oxygen species formation
Alkylating agents
  • ↓ DNA synthesis due to alkylation of DNA
  • ↓ DNA replication, protein synthesis
Table: Comparison of the cell cycle–dependent chemotherapy drugs
Drug classCell cycle phase affectedMechanism of action
AntifolatesCell cycle arrest at S phaseInhibit:
  • Dihydrofolate reductase
  • Thymidylate synthase
BleomycinCell cycle arrest at G2 phaseBinds DNA, leading to single- and double-stranded breaks
FluoropyrimidinesCell cycle arrest at S phaseInhibit thymidylate synthase
Deoxycytidine analogsCell cycle arrest at S phaseInhibit:
  • DNA polymerase
  • Ribonucleotide reductase
Purine analogsCell cycle arrest at S phaseInhibition of de novo purine synthesis
Topoisomerase II inhibitorsCell cycle arrest at S and G2 phasesInhibit topoisomerase II
TaxanesCell cycle arrest at metaphase of the M phaseHyperstabilization of microtubules
Vinca alkaloidsCell arrest during metaphase of the M phaseBinds to beta-tubulin and prevents microtubule polymerization


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