Metabolically Supported Chemotherapy for Managing End-Stage Breast Cancer: A Complete and Durable Response

Iyikesici, M. S.; Slocum, Abdul Kadir; Winters, Nasha; Kalamian, Miriam; Seyfried, Thomas N.

doi:10.7759/cureus.14686

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…It has not been studied whether ketogenic diet affects estrogen receptors. A case study reported that ketogenic diet, combined with several alternative therapies, induced a complete and durable response in an end-stage metastatic, ERa+ breast cancer patient (Iyikesici et al, 2021).…”

Section: Effects Of Ketogenic Diet On Icb Responsementioning

confidence: 99%

Foods may modify responsiveness to cancer immune checkpoint blockers by altering both the gut microbiota and activation of estrogen receptors in immune cells

Hilakivi‐Clarke¹,

Verma²,

McDermott³

et al. 2022

Front. Microbiom.

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Estrogen receptor alpha positive (ERα+) breast cancers are refractory to immune checkpoint blocker (ICB) monotherapy, while ICBs are part of a standard of care for triple negative breast cancers (TNBCs). Besides tumor ERα expression, another difference between the two types of breast cancers is that only ERα+ patients exhibit elevated tumor estradiol (E2) levels, compared with surrounding normal tissue. Recent evidence suggests that inhibition of ERα or activation of ERβ or G protein-coupled estrogen receptor (GPER) in immune cells in the tumor microenvironment (TME) increases tumor CD8+ T cell infiltration and boosts cancer ICB response. Ovarian and adipose-produced estrogens activate all three ERs equally, but plant estrogens (phytochemicals) preferentially activate ERβ or GPER. The gut microbiota is a key player in determining response to ICBs, and high abundance of Firmicutes and high fecal levels of short chain fatty acids (SCFAs) that are mainly produced by Firmicutes, are linked to improved effectiveness of ICB therapy. Interestingly, the gut microbiota of ERα+ breast cancer patients contain significantly lower abundance of Firmicutes species than the gut microbiota of TNBC patients. Many factors modify the gut microbiota, especially diet. The gut microbiota altering diets include (i) foods high in ERβ and GPER activating plant phytochemicals or (ii) SCFAs producing fiber that also reduces circulating estrogen levels, (iii) estrogen levels reducing fasting/caloric restriction, or (iv) ketogenic diet which reduces fecal SCFA levels but increases hepatic production of SCFA receptor activating ketone bodies. It is thus possible that certain foods or dietary patterns can modify both the gut microbiota and activation of the estrogen receptors in the tumor immune cells, and consequently regulate the effectiveness of ICB therapy against cancers.

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Section: Effects Of Ketogenic Diet On Icb Responsementioning

confidence: 99%

Foods may modify responsiveness to cancer immune checkpoint blockers by altering both the gut microbiota and activation of estrogen receptors in immune cells

Hilakivi‐Clarke¹,

Verma²,

McDermott³

et al. 2022

Front. Microbiom.

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Anti-cancer effects of hyperbaric oxygen therapy in mice: a meta-analysis

Klement,

Eckert,

Sweeney

2024

Oncologie

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Objectives Hypoxia is a ubiquitous condition in solid tumors and is associated with increased glycolysis, therapy resistance and disease progression. Hyperbaric oxygen therapy (HBOT) systemically elevates O2 tension in tissues and thus counteracts hypoxia. Here, we conducted a meta-analysis to quantify the effects of HBOT on survival in mice with cancer. Methods Studies retrieved from PubMed and Google Scholar were included if they allowed extracting restricted mean survival times in an HBOT-treated and control group. Meta-analyses were conducted using standardized mean differences (SMDs) and the log-transformed response ratio (lnRR) between the RMST of the treatment and control group with multilevel random effects models in order to account for non-independence of effect sizes. Publication bias was tested using a multilevel version of Egger’s regression. Results All studies applied HBOT with pressures between 2 and 3 atmospheres absolute (ATA). When administered without additional treatments, HBOT was associated with longer mouse survival times (pooled SMD=1.359 ± 0.624, p=0.0446; lnRR=0.065 ± 0.029, p=0.0399). Higher pressure was significantly associated with higher efficacy of hyperbaric oxygen monotherapy. When combined with chemotherapy, radiotherapy, targeted therapy or a ketogenic diet, HBOT was associated with significantly prolonged survival times compared to mice receiving these treatments without HBOT (SMD=2.696 ± 0.545, p<0.0001; lnRR=0.228 ± 0.042, p<0.0001). The combination of HBOT with chemotherapy was associated with lower efficacy than the combination with other treatment modalities. Conclusions We found weak evidence that HBOT prolongs survival times in cancer-bearing mice and strong evidence for synergistic effects with other therapies. The translational potential of these findings and extrapolation to lower-pressure HBOT remain to be determined.

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Metabolic management of microenvironment acidity in glioblastoma

et al. 2022

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Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondria and mitochondrial-associated membranes in GBM tissue. Glucose and glutamine are the major fermentable fuels that drive GBM growth. The major waste products of GBM cell fermentation (lactic acid, glutamic acid, and succinic acid) will acidify the microenvironment and are largely responsible for drug resistance, enhanced invasion, immunosuppression, and metastasis. Besides surgical debulking, therapies used for GBM management (radiation, chemotherapy, and steroids) enhance microenvironment acidification and, although often providing a time-limited disease control, will thus favor tumor recurrence and complications. The simultaneous restriction of glucose and glutamine, while elevating non-fermentable, anti-inflammatory ketone bodies, can help restore the pH balance of the microenvironment while, at the same time, providing a non-toxic therapeutic strategy for killing most of the neoplastic cells.

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Metabolically Supported Chemotherapy for Managing End-Stage Breast Cancer: A Complete and Durable Response

Cited by 3 publications

References 19 publications

Foods may modify responsiveness to cancer immune checkpoint blockers by altering both the gut microbiota and activation of estrogen receptors in immune cells

Foods may modify responsiveness to cancer immune checkpoint blockers by altering both the gut microbiota and activation of estrogen receptors in immune cells

Anti-cancer effects of hyperbaric oxygen therapy in mice: a meta-analysis

Metabolic management of microenvironment acidity in glioblastoma

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