Do intra-tumor alkaline micro-regions represent additional therapeutically privileged sites?
We briefly review some implications for therapeutic resistance in solid cancers that could be associated with more alkaline intra-tumor micro-regions reported to exist. Regions of increased alkalinity may provide a proliferative advantage for cancer "stem" or other cells, as more alkaline intra- and extra-cellular environments often are associated with increased cellular proliferation. If increased alkalinity is present in aerobic, but perhaps more especially in hypoxic micro-environments, proliferation of cells less susceptible to programmed cell death, with reduced expression of multi-drug resistance membrane proteins and altered efficacy of some therapeutic drugs should develop. Such cells are also more likely to generate aberrant clones resistant to additional therapy, particularly those dependent upon mitochondrial oxidative processes with greater generation of free radicals, compared to cells reliant on anaerobic glycolysis for metabolic energy. The interplay between alkalinity and normoxia, hypoxia or anoxia may differentially advantage some cancer "stem" cells.
Anderson
K M
KM
Hektoen Institute LLC, 627 S. Wood Street, Chicago, IL 60612, United States. kanderso427@sbcglobal.net
Jajeh
A
A
Guinan
P
P
Tsui
P
P
Rubenstein
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects
D000970:Antineoplastic Agents; D008565:Membrane Proteins