Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer

Furqan, Muhammad; Hejleh, Taher Abu; Stephens, Laura; Hartwig, Stacey M.; Mott, Sarah L.; Pulliam, Casey; Petronek, Michael; Henrich, John B.; Fath, Melissa A.; Houtman, Jon C. D.; Varga, Steven M; Bodeker, Kellie L.; Bossler, Aaron D.; Bellizzi, Andrew M.; Zhang, Jun; Monga, Varun; Mani, Hariharasudan; Ivanovic, Marina; Smith, Brian J.; Byrne, Margaret M.; Zeitler, William; Wagner, Brett A.; Buettner, Garry R.; Cullen, Joseph J.; Buatti, John M.; Spitz, Douglas R.; Allen, Bryan G.

doi:10.1016/j.redox.2022.102318

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…In combination with chemotherapeutics, this mechanism could lead to a further increase in ROS and diminish tumor survival. Thus, a recent phase II trial with VC and carboplatin–paclitaxel on non-small-cell lung cancer found an improved tumor response rate, although the combination therapy could not overcome mutations in the Nrf-2-Keap I complex [ 172 ]. Another study with ovarian cancer patients and a VC/DOX/paclitaxel regimen showed enhanced chemosensitivity and a reduction in chemotherapy-induced side effects; however, neither the difference in progression-free survival nor the overall survival rates differed significantly between the groups [ 204 ].…”

Section: Discussionmentioning

confidence: 99%

“…Chemotherapy-induced peripheral neuropathy (CIPN) is widely seen with patients under cisplatin or combined cisplatin therapies. A recent study combining high-dose vitamin C (intravenous) and carboplatin–paclitaxel regimen showed an improved immune response in non-small-cell lung cancer patients [ 172 ]. Two recent meta-analyses and a systematic review reported positive results, with vitamin E reducing CIPN incidence [ 18 , 173 , 174 ].…”

Section: The Critical Role Of Nrf-2-keap I In the Interplay Between C...mentioning

confidence: 99%

“…An earlier study with 32 patients found a lower incidence of paclitaxel-induced neurotoxicity in the vitamin E supplement arm [ 186 ]. High-dose intravenous vitamin C seems to have neuroprotective effects; however, the phase II clinical trial included patients ( n = 38) with a carboplatin–paclitaxel combination therapy [ 172 ].…”

Section: The Critical Role Of Nrf-2-keap I In the Interplay Between C...mentioning

confidence: 99%

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The Self-Administered Use of Complementary and Alternative Medicine (CAM) Supplements and Antioxidants in Cancer Therapy and the Critical Role of Nrf-2—A Systematic Review

Kuchheuser

Birringer

2022

Antioxidants

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Complementary and alternative medicine (CAM) supplements are widely used by cancer patients. Dietary supplements, vitamins and minerals, herbal remedies, and antioxidants are especially popular. In a systematic literature review, 37 studies, each including more than 1000 participants, on CAM, dietary supplement, and vitamin use among cancer patients were identified. Accordingly, cancer patients use antioxidants such as vitamin C (from 2.6% (United Kingdom) to 41.6% (United States)) and vitamin E (from 2.9% (China) to 48% (United States)). Dietary supplements and vitamins are taken for different reasons, but often during conventional cancer treatment involving chemotherapy or radiotherapy and in a self-decided manner without seeking medical advice from healthcare professionals. Drug–drug interactions with dietary supplements or vitamins involving multiple signaling pathways are well described. Since most of the anticancer drugs generate reactive oxygen species (ROS), an adaptive stress response of healthy and malignant cells, mainly driven by the Nrf-2-Keap I network, can be observed. On the one hand, healthy cells should be protected from ROS-overproducing chemotherapy and radiotherapy; on the other hand, ROS production in cancer cells is a “desirable side effect” during anticancer drug treatment. We here describe the paradoxical use of antioxidants and supplements during cancer therapy, possible interactions with anticancer drugs, and the involvement of the Nrf-2 transcription factor.

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Section: Discussionmentioning

confidence: 99%

Section: The Critical Role Of Nrf-2-keap I In the Interplay Between C...mentioning

confidence: 99%

Section: The Critical Role Of Nrf-2-keap I In the Interplay Between C...mentioning

confidence: 99%

See 1 more Smart Citation

The Self-Administered Use of Complementary and Alternative Medicine (CAM) Supplements and Antioxidants in Cancer Therapy and the Critical Role of Nrf-2—A Systematic Review

Kuchheuser

Birringer

2022

Antioxidants

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“…They suggested that ascorbate could be used as a simple, nontoxic agent to improve the outcome of radiation therapy for pancreatic cancer [ 261 , 262 ]. Several clinical trials are currently underway to investigate the safety and efficacy of pharmacological ascorbate in various malignancies, such as pancreatic cancer, glioma and lung cancer [ [263] , [264] , [265] ].…”

Section: Strategies For Enhancing Antitumor Effects Of Drug-induced O...mentioning

confidence: 99%

Drug-induced oxidative stress in cancer treatments: Angel or devil?

Jiang

Zuo

et al. 2023

Redox Biology

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“…The first evidence on pharmacological ascorbate as a modulator of anti-tumor immunity in humans was reported in a clinical trial where NSCLC patients received pharmacological ascorbate with carboplatin and paclitaxel, and those with progression-free survival ≥ 6 months showed enhanced CD8 + activation by 4.2 fold compared to 1.6 fold in patients with progression-free survival < 6 months ( 86 ). Through its role in regulating T cell maturation, differentiation, and activation, ascorbate is not only an immune modulator, but also a very promising regulator T cell mediated antitumor immunity.…”

Section: Ascorbate and Immune Regulationmentioning

confidence: 99%

Pharmacological ascorbate as a novel therapeutic strategy to enhance cancer immunotherapy

et al. 2022

Self Cite

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Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching ~ 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues. Immune checkpoint inhibitors (ICIs) are highly promising therapies for many cancer patients but face several challenges including low response rates, primary or acquired resistance, and toxicity. Ascorbate modulates both innate and adaptive immune functions and plays a key role in maintaining the balance between pro and anti-inflammatory states. Furthermore, the success of pharmacological ascorbate as a radiosensitizer and a chemosensitizer in pre-clinical studies and early phase clinical trials suggests that it may also enhance the efficacy and expand the benefits of ICIs.

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Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer

Cited by 9 publications

References 30 publications

The Self-Administered Use of Complementary and Alternative Medicine (CAM) Supplements and Antioxidants in Cancer Therapy and the Critical Role of Nrf-2—A Systematic Review

The Self-Administered Use of Complementary and Alternative Medicine (CAM) Supplements and Antioxidants in Cancer Therapy and the Critical Role of Nrf-2—A Systematic Review

Drug-induced oxidative stress in cancer treatments: Angel or devil?

Pharmacological ascorbate as a novel therapeutic strategy to enhance cancer immunotherapy

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