Program 2: Hypoxia-driven drug resistance


The hypoxic niche is a notorious driver of drug resistance

Rapidly expanding tumor masses can quickly outgrow their blood supply. Cancer cells in the resulting poorly vascularized areas suffer from a lack of oxygen and nutrients which triggers broad transcriptional and metabolic changes as cancer cells try to survive this state of deprivation. Similarly, anti-angiogenic cancer therapies that target the tumor vasculature to limit a tumors blood supply induce hypoxic niches. Hypoxic niches contain cancer cells that are notoriously aggressive and drug-resistant.

Using a hypoxia-sensing, 3D cancer microtissue-based screening technology, TOLREMO has identified novel vulnerabilities of hypoxic cancer cells. These vulnerabilities can be exploited to target the most aggressive kinds of cancer and to extend the clinical benefit of treatment modalities that are limited by hypoxia such as anti-angiogenic cancer drugs or radio- and chemotherapy.

As part of TOLREMO’s unique drug resistance platform, the company uses biochemical and high-content phenotypic assays to develop resistance-breaking molecules that exploit novel synthetic lethalities in hypoxic cancer cells. The company is currently advancing several chemical series that can be used as add-on therapies to make the clinical effects of anti-angiogenic inhibitors more durable.