Targeting ion transport in cancer

Abstract

The metabolism of cancer cells differs substantially from normal cells, including ion transport. Although this phenomenon has been long recognized, ion transporters have not been viewed as suitable therapeutic targets. However, the acidic pH values present in tumours which are well outside of normal limits are now becoming recognized as an important therapeutic target. Carbonic anhydrase IX (CAIX) is fundamental to tumour pH regulation. CAIX is commonly expressed in cancer, but lowly expressed in normal tissues and that presents an attractive target. Here, we discuss the possibilities of exploiting the acidic, hypoxic tumour environment as possible target for therapy. Additionally, clinical experience with CAIX targeting in cancer patients is discussed.

Keywords: carbonic anhydrase IX; clinical experience; targeting; translation; tumour acidity.

Figure 1.

SCID Beige mice were inoculated by intravenous injection with PC3M prostate cancer cells transfected to express firefly luciferase. Ad libitum drinking water for experimental animals contained 200 mM TRIS base, pH 8.4, whereas that for control animals was unadulterated. Tumour growth was monitored periodically using in vivo bioluminesce following injection of luciferin substrate. (Online version in colour.)

Figure 2.

Male, 62 years, presented with a renal cyst and a lesion suspect for RCC. (a) CT scan, arrow points to suspect lesion, (b) SPECT/CT image. Please note clear targeting of ¹¹¹indium-labelled mAbG250 in the suspect lesion on SPECT/CT, whereas no targeting of the cyst is visible. Minimal physiological uptake in the gastrointestinal tract. Histopathological examination after surgery confirmed the presence of ccRCC in the mAbG250-imaged lesion. (Online version in colour.)