Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming

Mattioli, Roberto; Ilari, Andrea; Colotti, Beatrice; Mosca, Luciana; Fazi, Francesco; Colotti, Gianni

doi:10.1016/j.mam.2023.101205

Cited by 51 publications

(23 citation statements)

References 630 publications

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“…Doxorubicin is an anthracycline antibiotic, and its analogs include daunorubicin, epirubicin and idarubicin. As a chemical drug, doxorubicin has a broad array of anticancer activities and is used to treat various cancers, especially hemangioma and solid tumors (Mattioli et al 2023 ). For most cancers, doxorubicin remains a first-line chemotherapy agent, either alone or in combination (Sritharan and Sivalingam 2021 ; Turinetto et al 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization

Yang,

Gui,

Zhang

et al. 2024

AMB Expr

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Doxorubicin is an important class of anthracycline antitumor antibiotics produced by Streptomyces peucetius. The doxorubicin fermentation yield of the wild-type strain was very low, so it could not be produced directly by fermentation at an industrial scale due to the high cost. In the present study, S. peucetius SIPI-7-14 was obtained from SIPI-14 through several rounds of doxorubicin resistance screening. Then, the ketoreductase gene dnrU was knocked out to reduce (13S)-13-dihydrodaunorubicin production, and the resistance gene drrC was overexpressed to further enhance resistance to doxorubicin. The resulting engineered strain S. peucetius △U1/drrC produced 1128 mg/L doxorubicin, a 102.1% increase compared to that of SIPI-14. Then, fermentation medium was optimized using the response surface method. In the optimized fermentation medium, the yield of doxorubicin was increased to 1406 mg/L in shake flask on the 7th day. Furthermore, batch culture was carried out in a 10 L fermenter, and the concentration of doxorubicin reached 1461 mg/L after 7 days of culture, which was the highest yield reported to date, indicating the potential for industrial production of doxorubicin by fermentation.

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Section: Introductionmentioning

confidence: 99%

Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization

Yang,

Gui,

Zhang

et al. 2024

AMB Expr

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“…High levels of MYB in osteosarcoma (OS) are correlated with poor prognosis and resistance, and MYB-knockout in OS cells provoked a sensitization to treatment with doxorubicin and the antimetabolite methotrexate [60] . MYB also prevented apoptosis induction by doxorubicin in CRC cells via activation of the NOX1-p38 axis [55] . The MYB-NOX1-p38 axis is also involved in resistance to platinum drugs, which underlines the role of this mechanistic pathway in the performance of different DNA-damaging drugs in CRC.…”

Section: Resistance To Other Dna-targeting Drugsmentioning

confidence: 91%

“…MYB expression was strongly upregulated in the p53-knockout cells compared with p53-wildtype cells, which might explain the multidrug-resistant phenotype of the p53-negative CRC cells and the poor prognosis for CRC with overexpressed MYB [54] . MYB also prevented apoptosis induction by cisplatin and oxaliplatin in CRC cells via increased expression of NADPH oxidase 1 (NOX1) followed by induction of pro-survival p38-mitogenactivated protein kinase (MAPK) signaling [55] . These results suggest that targeting the NOX1-p38 axis via specific inhibitors can become a suitable strategy for overcoming platinum resistance in CRC.…”

Section: Resistance To Platinum Complexesmentioning

confidence: 99%

Emerging role of MYB transcription factors in cancer drug resistance

Biersack,

Höpfner

2024

Cancer Drug Resist

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Decades ago, the viral myeloblastosis oncogene v -myb was identified as a gene responsible for the development of avian leukemia. However, the relevance of MYB proteins for human cancer diseases, in particular for solid tumors, remained basically unrecognized for a very long time. The human family of MYB transcription factors comprises MYB (c-MYB), MYBL2 (b-MYB), and MYBL1 (a-MYB), which are overexpressed in several cancers and are associated with cancer progression and resistance to anticancer drugs. In addition to overexpression, the presence of activated MYB-fusion proteins as tumor drivers was described in certain cancers. The identification of anticancer drug resistance mediated by MYB proteins and their underlying mechanisms are of great importance in understanding failures of current therapies and establishing new and more efficient therapy regimens. In addition, new drug candidates targeting MYB transcription factor activity and signaling have emerged as a promising class of potential anticancer therapeutics that could tackle MYB-dependent drug-resistant cancers in a more selective way. This review describes the correlation of MYB transcription factors with the formation and persistence of cancer resistance to various approved and investigational anticancer drugs.

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“…Doxorubicin (DOX), a member of the Anthracyclines family, is widely used in chemotherapy against a variety of malignancies such as breast, genitourinary, and ovarian cancers; Hodgkin's and non-Hodgkin's lymphomas; Ewing and soft tissue sarcoma; lymphocytic and myelogenous leukemias; gastrointestinal, liver, and thyroid cancers; and neuroblastoma [42,43]. The molecular mechanisms of DOX's impact on cancer cells include intercalation into the DNA-topoisomerase II complex, which causes DNA damage, followed by p53-mediated cell cycle arrest, alterations in the redox state due to ROS accumulation and iron-dependent lipid peroxidation, the dysregulation of calcium-binding proteins and channels, and increased production of interleukins and interferons facilitating the immune-driven clearance of tumor cells.…”

Section: Chloroquine and Doxorubicin (Dox)mentioning

confidence: 99%

Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment

Agalakova

2024

IJMS

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Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ), the compounds with recognized ability to suppress autophagy, have been tested in experimental works and in clinical trials as adjuvant therapy for the treatment of tumors of different origin to increase the efficacy of cytotoxic agents. Such a strategy can be effective in overcoming the resistance of cancer cells to standard chemotherapy or anti-angiogenic therapy. This review presents the results of the combined application of CQ/HCQ with conventional chemotherapy drugs (doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinases and PI3K/Akt/mTOR inhibitors, and other agents) for the treatment of different malignancies obtained in experiments on cultured cancer cells, animal xenografts models, and in a few clinical trials. The effects of such an approach on the viability of cancer cells or tumor growth, as well as autophagy-dependent and -independent molecular mechanisms underlying cellular responses of cancer cells to CQ/HCQ, are summarized. Although the majority of experimental in vitro and in vivo studies have shown that CQ/HCQ can effectively sensitize cancer cells to cytotoxic agents and increase the potential of chemotherapy, the results of clinical trials are often inconsistent. Nevertheless, the pharmacological suppression of autophagy remains a promising tool for increasing the efficacy of standard chemotherapy, and the development of more specific inhibitors is required.

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Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming

Cited by 51 publications

References 630 publications

Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization

Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization

Emerging role of MYB transcription factors in cancer drug resistance

Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment

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