Anticancer Therapy Targeting Hypoxic Tumour Microenvironment¹

Hypoxia is a common feature of solid tumours, and develops because of the rapid growth of the tumour that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumour. Intra-tumoural hypoxia promotes metabolic reprogramming by tumour cells in order to meet energy and biosynthetic demands in a low-oxygen environment, whereas the processes induce intracellular acidification and impacting cell viability. In hypoxic tumours, carbonic anhydrases (CA) IX (CAIX) activity enables the maintenance of an intracellular pH favourable for cancer cell survival and growth, and simultaneously contributes to extracellular acidification, facilitating tumour cell migration, invasion and metastasis, and therapeutic resistance. SLC-0111 is a selective inhibitor of CAIX which decreases glycolytic metabolism of tumour cells and acidification of the hypoxic tumour microenvironment. A recent Phase-I trial on patients with advanced solid tumours and for which standard curative measures did not exist demonstrated that 1000 mg/day SLC-0111 was safe and cases of stable disease >24 weeks were observed. Hence, Phase-II trial of the treatment is warranted. In addition, further investigations on the therapeutic impact of treatment combining SLC-0111 and existing therapies are desirable.

References

1 McDonald et al. Am J Clin Oncol Cancer Clin Trials 2020; 43: 484-90.