CLINICAL PROBLEM

HYPOXIA is a critical factor in tumour drug resistance, resulting in:

• poor penetration of conventional chemotherapy and immunotherapy - due to poor blood supply
• lack of oxygen to support effective radiotherapy
• amplification of Hypoxia Inducible Factor (HIF) mediated tumour cell survival and proliferation

In every solid tumour there are regions that are starved of oxygen. This happens because tumour cells divide rapidly and as they do so, some cells move away from the blood supply, creating low oxygen microenvironments. Most cells cannot survive without an oxygen supply, but some resistant cancer cells are able to switch their metabolism and effectively lie dormant in these hypoxic microenvironments.

The problem is that conventional chemotherapy, immunotherapy and radiotherapy do not treat hypoxic cancer cells, so unfortunately they lie waiting for an opportunity to reconnect to the blood supply. When they do, the presence of oxygen allows them to switch back to normal metabolism, whereupon they rapidly divide and spread.

OUR SOLUTION

unidirectional Hypoxia-Activated Prodrugs (uHAPs) given alongside conventional therapy:

• penetrate the whole tumour and in hypoxic tumour cells are converted to a known and highly effective anticancer agents known as Topo 2a inhibitors.

Our solution is to target the hypoxic microenvironment with a new class of pro-drugs. Our new pro-drugs are able to penetrate the whole tumour including the difficult to reach hypoxic regions. When they reach a hypoxic cancer cell, the prodrug is metabolised into a highly effective and persistent Topo 2a Isomerase inhibitor. So, by giving our unidirectional Hypoxia Activated Prodrugs alongside conventional chemotherapy, we are ensuring the effective treatment of the whole tumour.