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Systemic buffers inhibit carcinogenesis in TRAMP mice.

Arig Ibrahim-Hashim1, Heather H Cornnell, Dominique Abrahams

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Altering the tumor microenvironment by reducing acidity with sodium bicarbonate can prevent prostate cancer development in mice. Early intervention is key to preventing cancer evolution and progression.

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Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment

Background:

  • In situ tumors develop hypoxia and acidosis due to cellular expansion, increasing diffusion distances.
  • Adaptation to microenvironmental hypoxia and acidosis correlates with the transition from in situ to invasive cancer in breast and cervical cancers.

Purpose of the Study:

  • To test the hypothesis that decreased acidosis in intraductal tumors alters selection pressures, delaying or preventing evolution to invasive cancer.
  • To investigate the effect of sodium bicarbonate on prostate cancer development in TRAMP mice.

Main Methods:

  • 37 C57BL/6 TRAMP mice were randomized into control and treatment groups.
  • Sodium bicarbonate (200 mM) was administered in drinking water to treatment groups, starting between 4 and 10 weeks of age.

Main Results:

  • All 18 control mice developed prostate cancer by a mean age of 13 weeks.
  • Mice receiving sodium bicarbonate before 6 weeks of age reached senescence without radiographic evidence of cancer (70% showed hyperplasia, not cancer).
  • Mice receiving therapy after 6 weeks of age showed no difference in cancer development compared to controls.

Conclusions:

  • Early intervention with sodium bicarbonate prevents prostate cancer development in TRAMP mice.
  • Reduced acidosis in in situ tumors may serve as a cancer prevention strategy.
  • Carbonic anhydrase 9 expression was lower in the early treatment group compared to controls.