The role of biophysics and engineering in investigating tumour pH and its regulation

Solid tumours tend to have a high metabolic rate, inducing the intracellular accumulation of lactic acid and CO 2 with a concomitant decrease in pH. Since many intracellular processes are pH-sensitive, tumour progression is therefore dependent on the maintenance of intracellular and extracellular pH within a narrow range. Cancer cells employ a number of functionally redundant regulatory mechanisms to maintain pH homeostasis. Several small molecule inhibitors which target these mechanisms are currently in clinical trials with promising outcomes. In order to investigate tumour pH regulation and to stratify and monitor patient response to these treatments, we need to be able to accurately measure pH in situ . Although pH measurement techniques are continually being developed, they are still limited for example by poor probe targeting and spatio-temporal resolution. In this review, we discuss the important role of biophysics and engineering in tackling the challenges faced when measuring tumour pH.