Robet Gatenbt, Moffit Cancer Center, "Tumor physical microenvironment from Mathematical Models to Clinical Trials"

"Cancer is a disease of the genes": not a complete picture.

Cancer is not at all homogeneous.  Better viewed as a multi-scale tissue ecosystem

Cancer is a disease of evolution:

1. Somatic mutations occur
2. Failure of host defenses to deal with those changes

 PET imaging: uses FDG (f-deoxyglucose).  Cancer cells take up glucose at a much higher rate, easily imaged.  Result:

Glycolosys is a hallmark of cancer

Tumors are hypoxic.  Cause: "oxygen inhibits the fermentation of glucose." (Louis Pasteur, 1855)... but "tumors have a remakable capacity to ferment glucose even in the presence of oxygen (Otto Warberg, 1934).  So, increased glucose uptake does not necessarily correlate with hypoxia. (Pasteur and Warberg effects)




Cancer grows on an epithelial membrane: blood on one side, cancer cells on other.  As they develop away from the membrane:

• less oxygen available
• more acidic
• => already adapted to this environment (Warberg effect)

Question: why does hypoxic glycolosis increase fitness advantage?

• produces more acid: toxic to normal cells
• doesn't require oxygen (required by normal cells
• => well adapted to their environment

Hypotheses:

• adding sodium bicarbonate (base) to the tumor environment reduced tumor growth 
• tumor-associated pain related to acidic environment

 Testing these hypotheses:

• Shown to be true (missed ref...)
• About to start clinical trials of oral ingestion of sodium bicarbonate in conjunction with prostate cancer treatment
• Does not change pH of blood!  But does change pH of tumor region (from animal studies)
• Looking at other buffers for clinical use (because of high sodium content of sodium bicarbonate)