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Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions.

ABSTRACT: Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

SUBMITTER: Fu L

PROVIDER: S-EPMC8897051 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions.

Fu Leilei L Jin Wenke W Zhang Jiahui J Zhu Lingjuan L Lu Jia J Zhen Yongqi Y Zhang Lan L Ouyang Liang L Liu Bo B Liu Bo B Yu Haiyang H

Acta pharmaceutica Sinica. B 20210910 2

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new eme ...[more]

PMID: 35256933

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Project description:ObjectivesTo evaluate lung cancer (LC) risk factor awareness among Palestinians and identify factors associated with good awareness.DesignCross-sectional study.SettingsParticipants were recruited using convenience sampling from hospitals, primary healthcare centres (PHCs) and public spaces located at 11 governorates in Palestine.ParticipantsOf 5174 approached, 4817 participants completed the questionnaire (response rate=93.1%). A total of 4762 questionnaires were included: 2742 from the West Bank and Jerusalem (WBJ) and 2020 from the Gaza Strip. Exclusion criteria were working or studying in a health-related field, having a nationality other than Palestinian and visiting oncology departments or clinics at the time of data collection. TOOL: A modified version of the validated LC Awareness Measure was used for data collection.Primary and secondary outcomesThe primary outcome was LC risk factor awareness level as determined by the number of factors recognised: poor (0-3), fair (4-7) and good (8-10). Secondary outcomes include the recognition of each LC risk factor.ResultsSmoking-related risk factors were more often recognised than other LC risk factors. The most recognised risk factors were 'smoking cigarettes' (n=4466, 93.8%) and 'smoking shisha (waterpipes)' (n=4337, 91.1%). The least recognised risk factors were 'having a close relative with LC' (n=2084, 43.8%) and 'having had treatment for any cancer in the past' (n=2368, 49.7%).A total of 2381 participants (50.0%) displayed good awareness of LC risk factors. Participants from the WBJ and the Gaza Strip had similar likelihood to display good awareness (50.6% vs 49.1%). Being≥45 years, having higher education and monthly income, knowing someone with cancer and visiting hospitals and PHCs seemed to have a positive impact on displaying good awareness.ConclusionHalf of study participants displayed good awareness of LC risk factors. Educational interventions are warranted to further improve public awareness of LC risk factors, especially those unrelated to smoking.

Project description:Glucocorticoids are the most effective anti-inflammatory therapy for asthma yet are relatively ineffective in chronic obstructive pulmonary disease. Glucocorticoids suppress inflammation via several molecular mechanisms. Glucocorticoids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, by reversing histone acetylation of activated inflammatory genes through binding of ligand-bound glucocorticoid receptors (GR) to co-activator molecules and recruitment of histone deacetylase-2 to the activated inflammatory gene transcription complex (trans-repression). At higher concentrations of glucocorticoids GR homodimers interact with DNA recognition sites to activate transcription through increased histone acetylation of anti-inflammatory genes and transcription of several genes linked to glucocorticoid side effects (trans-activation). Glucocorticoids also have post-transcriptional effects and decrease stability of some pro-inflammatory mRNA species. Decreased glucocorticoid responsiveness is found in patients with severe asthma and asthmatics who smoke, as well as in all patients with chronic obstructive pulmonary disease. Several molecular mechanisms of glucocorticoid resistance have now been identified which involve post-translational modifications of GR. Histone deacetylase-2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti-inflammatory actions of glucocorticoids. Dissociated glucocorticoids and selective GR modulators which show improved trans-repression over trans-activation effects have been developed to reduce side effects, but so far it has been difficult to dissociate anti-inflammatory effects from adverse effects. In patients with glucocorticoid resistance alternative anti-inflammatory treatments are being investigated as well as drugs that may reverse the molecular mechanisms of glucocorticoid resistance.

Dataset Information

Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions.

Publications

Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions.

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