Press-pulse: a novel therapeutic strategy for the metabolic management of cancer 癌症代謝管理的新治療策略

中文版谷歌中文翻譯(90% 準確率) | English translation
Buy/Sell Your Domains Here。在這裡購買/出售您的域名
Contact Dr. Lu for information about cancer treatments。聯繫盧博士,獲取有關癌症治療資訊。

Discussion & Conclusions

Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease. It is clear from the cancer death statistics that most current therapies are wanting in their ability to reduce the yearly death rate or to manage the disease without toxicity. Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival. Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment. The press-pulse therapeutic strategy is designed to target availability of glucose and glutamine thus starving tumor cells of their most important fuels and increasing their vulnerability to oxidative stress and apoptotic death. Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides. DON and other similar glutamine inhibitors will deprive proliferating tumor cells of the glutamine needed for TCA cycle anaplerosis, and synthesis of glutathione, nucleotides, and proteins. Lysosomal targeting with chloroquine or similar drugs will reduce glucose and glutamine production following digestion of phagocytosed glycoconjugates and proteins. Glutamine targeting will require careful adjustments, however, as glutamine is a key metabolite needed for the immune system and for other physiological functions. Hyperbaric oxygen therapy combined with the calorie restricted ketogenic diet will kill tumor cells through apoptotic and anti-angiogenic mechanisms while also reducing inflammation in the tumor microenvironment and systemically. It is our view that the “Press-Pulse” paradigm is a compelling and parsimonious therapeutic strategy for effectively managing the vast majority of malignant cancers with minimal toxicity, as this approach will target the major energy pathways responsible for tumor cell growth and survival while enhancing the energetic efficiency of normal body cells and tissues.

Abbreviations

2-DG: 

2-deoxyglucose

CR: 

Calorie restriction

DON: 

6-diazo-5-oxo-L-norleucine

FAD: 

Flavin adenine dinucleotide

GBM: 

Glioblastoma multiforme

GKI: 

Glucose Ketone Index

HBOT: 

Hyperbaric oxygen therapy

KD-R: 

Restricted Ketogenic Diet

NAD: 

Nicotinamide adenine dinucleotide

ROS: 

Reactive Oxygen Species

SLP: 

Substrate level phosphorylation

TCA: 

Tricarboxylic acid

Declarations

Acknowledgements

We would also like to thank Zachary Augur and Michael Pool for technical assistance, Drs. Purna Mukherjee, Angela Poff, and Andrew Koutnik for valuable comments, and the late Madam Trudy Dupont for providing us with valuable information and insight on the human experience of metabolic therapy for brain cancer management.

Funding

Single Cause, Single Cure Foundation, the George Yu Foundation, Dave Woynarowski, Ellen Davis, Lewis Topper, the Boston College Research. Expense Fund, the Nelson and Claudia Peltz Foundation, and the Boston.College Biology Department Cancer Fund, and Scivation.

Availability of data and material

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Authors’ contributions

TNS wrote most of the manuscript with the assistance of DPD, GY, and JCM. All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

NA.

Ethics approval and consent to participate

NA.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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