Abstract
Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer “pH gradient reversal”. Normalizing pH gradient reversal through inhibition of various proton transporters such as Na+-H+ exchanger (NHE), Vacuolar-type H+-ATPase (V-ATPase), H+/K+-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.
Keywords: Apoptosis, cancer, migration, pH, proliferation, tumor invasion.
Recent Patents on Anti-Cancer Drug Discovery
Title:pH Gradient Reversal: An Emerging Hallmark of Cancers
Volume: 10 Issue: 3
Author(s): Mohit Sharma, Madhusudan Astekar, Sonal Soi, Bhari S. Manjunatha, Devi C. Shetty and Raghu Radhakrishnan
Affiliation:
Keywords: Apoptosis, cancer, migration, pH, proliferation, tumor invasion.
Abstract: Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer “pH gradient reversal”. Normalizing pH gradient reversal through inhibition of various proton transporters such as Na+-H+ exchanger (NHE), Vacuolar-type H+-ATPase (V-ATPase), H+/K+-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.
Export Options
About this article
Cite this article as:
Sharma Mohit, Astekar Madhusudan, Soi Sonal, S. Manjunatha Bhari, C. Shetty Devi and Radhakrishnan Raghu, pH Gradient Reversal: An Emerging Hallmark of Cancers, Recent Patents on Anti-Cancer Drug Discovery 2015; 10 (3) . https://dx.doi.org/10.2174/1574892810666150708110608
DOI https://dx.doi.org/10.2174/1574892810666150708110608 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
Call for Papers in Thematic Issues
Novel anti-cancer drugs in photoimmunotherapy management: from bench to translational research
In recent years, traditional cancer treatments, such as surgery, chemotherapy, and radiation treatment, etc., may damage the pathological tissue and normal cells. The ideal tumor treatment should be noninvasive, eliminating the primary tumor, making the body produce systemic tumor-specific immunity, eliminating metastases, and having less /no side effects. Recent Patents ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
ABC Subfamily D Proteins and Very Long Chain Fatty Acid Metabolism as Novel Targets in Adrenoleukodystrophy
Current Drug Targets Exploring Patterns of Epigenetic Information with Data Mining Techniques
Current Pharmaceutical Design Thermal N-9 → N-7 Isomerization of (6-Substituted)-9-(2,3-Dihydro-5H-1,4-Benzodioxepin-3-yl)-9H-Purines in Solution: Mechanistic Aspects
Mini-Reviews in Organic Chemistry Purine Nucleoside Analogues for the Treatment of Hematological Malignancies: Pharmacology and Clinical Applications
Current Cancer Drug Targets Natural Anti-Cancer Agents: Implications in Gemcitabine-Resistant Pancreatic Cancer Treatment
Mini-Reviews in Medicinal Chemistry Rho Kinase and Angiogenesis
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Knee Meniscus Segmentation and Tear Detection from MRI: A Review
Current Medical Imaging Dual Antibacterial and Anticancer Activity of 4-Benzoyl-1-dichlorobenzoylthiosemicarbazide Derivatives
Anti-Cancer Agents in Medicinal Chemistry Radiolabelled Probes Targeting Tumor Hypoxia for Personalized Medicine
Current Pharmaceutical Design PREFACE [Hot topic: Current Concepts in Assisted Reproduction and Fertility Preservation (Part II) (Guest Editors: Sajal Gupta and Ashok Agarwal)]
Current Women`s Health Reviews Improving the Stability of Aptamers by Chemical Modification
Current Medicinal Chemistry Design of Rhenium Compounds in Targeted Anticancer Therapeutics
Current Pharmaceutical Design Bioprocessing of Baculovirus Vectors: A Review
Current Gene Therapy Enzymes Oxidizing the Azo Dye 1-Phenylazo-2-Naphthol (Sudan I) and their Contribution to its Genotoxicity and Carcinogenicity
Current Drug Metabolism Biodistribution, Safety and Organ Toxicity of Docetaxel-Loaded in HER-2 Aptamer Conjugated Ecoflex® Nanoparticles in a Mouse Xenograft Model of Ovarian Cancer
Recent Patents on Nanotechnology Nanomagnets-From Fundamental Physics to Biomedicine
Current Nanoscience Antibacterial and Antitumorigenic Properties of Microcin E492, a Pore- Forming Bacteriocin
Current Pharmaceutical Biotechnology HtrA Protease Family as Therapeutic Targets
Current Pharmaceutical Design Endocannabinoids and Their Receptors: Physiology, Pathology and Pharmacology
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Burden of Bronchiectasis in Indigenous Peoples - How Can it be Improved?
Current Pediatric Reviews