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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Also known as actinomycin-D, dactinomycin (Cosmegen), is one of a group of antibiotics produced by various species of streptomyces (the actinomycins). Dactinomycin is approved to treat choriocarcinoma, Ewing’s and Wilms tumors, rhabdomyosarcoma, and testicular and uterine cancers. Dactinomycin is indicated in obstetrics to treat gestational trophoblastic tumors.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Administered intravenously, dactinomycin is mainly used to treat pediatric cancers. For example, in the UK it is mainly used to treat Wilms’ tumor, childhood rhabdomyosarcoma, and other soft-tissue sarcomas, and Ewing’s sarcoma. However, it has also been used for some testicular sarcomas and for AIDS-related Kaposi’s sarcoma. Sometimes it is used in combination with other agents (e.g., gestational choriocarcinoma and Wilm’s tumor in combination with methotrexate or vincristine, respectively).
Respiratory, endocrine, cardiac, and renal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Dactinomycin is used in the treatment of different solid tumours (nephroblastoma, sarcomas). The usual dose is 15 mcg/kg per day for 5 consecutive days. If irradiation is used, dactinomycin must be significantly reduced to avoid hepatotoxicity. Dactinomycin is toxic to the veins and any extravasation must lead to an immediate cessation of the administration, as well as to a local injection of sodium thiosulfate.
Lurbinectedin: an FDA-approved inducer of immunogenic cell death for the treatment of small-cell lung cancer
Published in OncoImmunology, 2020
Oliver Kepp, Laurence Zitvogel, Guido Kroemer
We recently performed a systematic analysis of chemotherapeutic drugs, observing that drugs that inhibit transcription are particularly efficient ICD inducers. Thus, dactinomycin (also known as actinomycin D), a prototypic inhibitor of transcription that has been used for this purpose by generations of cellular and molecular biologists, turned out to be a particularly efficient ICD inducer that causes tumor growth control in preclinical models only if the immune system is intact, through a T cell-dependent mechanism that can be boosted by combination with PD-1 blockade.8 Lurbinectedin is a cytotoxicant that binds to DNA and inhibits transcription.10 Accordingly, lurbinectedin also triggers ICD and induces potent anticancer immune responses in preclinical models.11
Recent progress in the repurposing of drugs/molecules for the management of COVID-19
Published in Expert Review of Anti-infective Therapy, 2021
Divakar Sharma, Adinarayana Kunamneni
Actinomycin D is used for the treatment of various types of cancer. It activates the p53 that subsequently leads to the upregulation of crucial regulators and effectors like interferons [46]. Coronavirus (SARS-CoV) encoded papain-like protease (PLpro), which degrades the p53 and leads to the suppression of the interferon signaling [47]. So the use of actinomycin D may trigger the expression of the p53 that subsequently leads to stimulation of the interferon signaling/interferon production. These interferons could be helpful to combat the COVID-19. Based on these facts, we suggested the repurposing of this drug against COVID-19.
Mechanistic modelling of targeted pulmonary delivery of dactinomycin iron oxide-loaded nanoparticles for lung cancer therapy
Published in Pharmaceutical Development and Technology, 2022
Shahd F. Al-Tarawneh, Eman Zmaily Dahmash, Hamad Alyami, Suha M. Abu-Doleh, Samer Al-Ali, Affiong Iyire, Rasha Abuthawabeh
Dactinomycin was selected as a model API owing to its pharmacological effect for the treatment of local solid tumours. Also, being a large molecule with molecular weight of 1255.4 g/mol (Gwaltney-Brant 2010), presented an opportunity to assess a challenging molecule in nanoparticle development. Chitosan and Na alginate were chosen as model polymers as they are biocompatible, widely used in nanoparticle development, have mucoadhesive properties, aid extended release from formulations and have several reported potential applications in drug delivery to the pulmonary system (Jana and Jana 2016; Maiti and Kumari 2016).