Project description
New target in combinatorial breast cancer treatment
Targeted precision medicine in combination with companion diagnostics (a diagnostic test to determine the applicability of the therapeutic drug to a specific person) represents an attractive option for effective patient care. Recent advances in breast cancer treatment using a combination of targets are at the forefront of this development. The recently discovered Nudix-linked to moiety X-5 enzyme (NUDIX5) plays a role in adenosine triphosphate generation in the nucleus. Overexpression of the NUDIX5 in breast and other types of cancer has been associated with a poor prognosis and increased risk of recurrence and metastasis. The EU-funded IMPACCT project proposes to determine if the developed NUDIX5 inhibitors, in combination with companion diagnostics, can be used as a targeted treatment in breast cancer patients.
Objective
Targeted precision medicine combined with companion diagnostics will provide the basis for future more effective more economic patient care. Recent advances in breast cancer treatment combining inhibitors of poly-ADP-ribose polymerase (PARP1) in conjunction with other targets are at the forefront of this new advance both at the level of basic research and pharmaceutical interest, due to its pivotal role in gene expression, chromatin and repair. We have discovered a key enzyme downstream of PARP1 which generates ATP locally in the nucleus; NUDIX5. This enzyme is overexpressed in cancer and correlates with poor prognosis, as the activity of this enzyme is essential for changes within the 3D chromatin structure, gene regulation and the proliferation of cancer cells. We have developed inhibitors of NUDIX5 in addition to a companion diagnostic, and propose to prove using a multi-disciplinary, international collaborative effort that they can be used to determine not only patient risk and treatment options but also provide an exciting new avenue for the combinatorial treatment of breast and (we hope) other cancer patients.
Fields of science
Programme(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
08003 Barcelona
Spain