A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3)

Trimble, Cornelia L.; Levinson, Kimberly; Maldonado, Leonel; Donovan, Michael; Clark, Katharine; Fu, Jie; Shay, Maria E.; Sauter, Mary Elizabeth; Sanders, Stephanie A.; Frantz, Peter S.; Plesa, Mihaela

doi:10.1016/j.ygyno.2019.12.035

Cited by 44 publications

(52 citation statements)

References 27 publications

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“…Artemisinins have also been shown to regulate the process of autophagy ( Trimble, Levinson, Maldonado, et al, 2020 ). Autophagy is a degradative process of recycling organelles and cytoplasmic content in order to maintain cellular haemostasis and involves multiple signaling pathways.…”

Section: Artemisinins: Effects On Cancer Cell Death Pathwaysmentioning

confidence: 99%

“…Autophagy is a degradative process of recycling organelles and cytoplasmic content in order to maintain cellular haemostasis and involves multiple signaling pathways. Cancer cells dysregulate autophagy as a tumour adaptation mechanism in nutrient-deplete tumour microenvironments ( Trimble et al, 2020 ). DHA has been shown to switch off activity of NF-κB, leading to upregulation of autophagy in several cancer cell lines.…”

Section: Artemisinins: Effects On Cancer Cell Death Pathwaysmentioning

confidence: 99%

“…The addition of heme synthesis precursor aminolevulinic acid (ALA) to artesunate treatment was found to dramatically enhance cytotoxicity in a mouse xenograft CRC model ( Wang et al, 2017 ). The ability of artemisinins to target multiple cancer pathways may allow it to target various cancer types as well as evade chemoresistance ( Trimble et al, 2020 ).…”

Section: Future Perspectives: Strategies To Enhance Artesunate Cytotomentioning

confidence: 99%

“…Artesunate combination therapy with other existing established anticancer therapies has also shown synergistic effects in a number of cancer cell line models ( Trimble et al, 2020 ). Artesunate synergistically enhanced the inhibitory effect of tyrosine kinase inhibitor sorafenib on cell growth in HepG2 and Huh7 hepatocellular cancer cells lines ( Li et al, 2019 ).…”

Section: Future Perspectives: Strategies To Enhance Artesunate Cytotomentioning

confidence: 99%

“…A Phase I dose-escalation study of artesunate vaginal inserts in biopsy-confirmed Cervical Intraepithelia Neoplasia (CIN)2/3 conducted in 28 patients showed that treatment was safe, well tolerated ( Trimble et al, 2020 ). Patients with CIN 2/3 received 1, 2, or 3 five-day treatment cycles at study weeks 0, 2, and 4, respectively, prior to a planned, standard-of-care resection at study week 15.…”

Section: Clinical Translational Studies Of Artemisinins As Anti-cancementioning

confidence: 99%

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Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing

Augustin

Staines

Krishna

2020

Pharmacology & Therapeutics

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Artemisinins are a unique class of antimalarial drugs with significant potential for drug repurposing for a wide range of diseases including cancer. Cancer is a leading cause of death globally and the majority of cancer related deaths occur in Low and Middle Income Countries (LMICs) where conventional treatment options are often limited by financial cost. Drug repurposing can significantly shorten new therapeutic discovery pathways, ensuring greater accessibility and affordability globally. Artemisinins have an excellent safety and tolerability profile as well as being affordable for deployment in Low and Middle Class Income Countries at around USD1 per daily dose. Robust, well designed clinical trials of artemisinin drug repurposing are indicated for a variety of different cancers and treatment settings.

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Section: Artemisinins: Effects On Cancer Cell Death Pathwaysmentioning

confidence: 99%

Section: Artemisinins: Effects On Cancer Cell Death Pathwaysmentioning

confidence: 99%

Section: Future Perspectives: Strategies To Enhance Artesunate Cytotomentioning

confidence: 99%

Section: Future Perspectives: Strategies To Enhance Artesunate Cytotomentioning

confidence: 99%

Section: Clinical Translational Studies Of Artemisinins As Anti-cancementioning

confidence: 99%

See 3 more Smart Citations

Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing

Augustin

Staines

Krishna

2020

Pharmacology & Therapeutics

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Therapeutical Utilization and Repurposing of Artemisinin and Its Derivatives: A Narrative Review

Lin

Wang

et al. 2023

Advanced Biology

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Artemisinin (ART) and its derivatives have great therapeutical utility as antimalarials and can be repurposed for other indications, such as viral infections, autoimmune diseases, and cancer. This review presents a comprehensive overview of the therapeutic effects of ART‐based drugs, beyond their antimalarial effects. This review also summarizes the information on their repurposing in other pathologies, with the hope that it will guide the future optimization of the use of ART‐based drugs and of the treatment strategies for the listed diseases. By reviewing related literature, ART extraction and structure as well as the synthesis and structure of its derivatives are presented. Subsequently, the traditional roles of ART and its derivatives against malaria are reviewed, including antimalarial mechanism and occurrence of antimalarial resistance. Finally, the potential of ART and its derivatives to be repurposed for the treatment of other diseases are summarized. The great repurposing potential of ART and its derivatives may be useful for the control of emerging diseases with corresponding pathologies, and future research should be directed toward the synthesis of more effective derivatives or better combinations.

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Potential effectiveness of a therapeutic HPV intervention campaign in Uganda

Spencer

Campos²,

Burger

et al. 2021

Intl Journal of Cancer

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Cervical cancer is a major source of morbidity and mortality in Uganda. In addition to prophylactic HPV vaccination, secondary prevention strategies are needed to reduce cancer burden. We evaluated the potential cancer reductions associated with a hypothetical single-contact therapeutic HPV intervention-with 70% coverage and variable efficacy [30%-100%]-using a three-stage HPV modeling framework reflecting HPV and cervical cancer burden in Uganda. In the reference case, we assumed prophylactic preadolescent HPV vaccination starting in 2020 with 70% coverage. A onetime therapeutic intervention targeting 35-year-old women in 2025 (not age-eligible for prophylactic vaccination) averted 1801 cervical cancers per 100 000 women over their lifetime (100% efficacy) or 533 cancers per 100 000 (30% efficacy). Benefits were considerably smaller in birth cohorts eligible for prophylactic HPV vaccination (768 cases averted per 100 000 at 100% efficacy). Evaluating the population-level impact over 40 years, we found introduction of a therapeutic intervention in 2025 with 100% efficacy targeted annually to 30-year-old women averted 139 000 incident cervical cancers in Uganda. This benefit was greatly reduced if efficacy was lower (30% efficacy; 41 000 cases averted), introduction was delayed (2040 introduction; 72 000 cases averted) or both (22 000 cases averted). We demonstrate the potential benefits of a single-contact HPV therapeutic intervention in a low-income setting, but show the importance of high therapeutic efficacy and early introduction timing relative to existing prophylactic programs. Reduced benefits from a less efficacious intervention may be somewhat offset if available within a shorter time frame.

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A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3)

Cited by 44 publications

References 27 publications

Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing

Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing

Therapeutical Utilization and Repurposing of Artemisinin and Its Derivatives: A Narrative Review

Potential effectiveness of a therapeutic HPV intervention campaign in Uganda

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