Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

Hhat inhibition as a novel approach for selective cancer treatment

Project description

The role of the Hhat protein-coding gene in cancer treatment

Hedgehog signalling molecules are involved in many biological events including cell differentiation, proliferation and survival, as well as ageing and the establishment of the body plan. An abnormal expression or mutations of Hedgehog pathway genes cause a variety of genetic disorders at different stages, including cancer. Inhibition of the Hedgehog pathway showed some success in the clinic, but resistance development is a common problem, creating demand for an alternative Hedgehog modulator. Hhat is a membrane-associated O-acyl transferase that carries out Hedgehog posttranslational palmitoylation, critical for its signalling. The EU-funded HHAT project proposes to develop selective high potency Hhat inhibitors and investigate their cellular activity to validate Hhat as a target in cancer therapy.

Objective

Being the first or second most common cause of premature death in over 100 countries, cancer imposes a major burden on modern societies worldwide. Inhibition of the Hedgehog pathway has had success, both in vitro and in the clinic, but resistance is a commonly encountered problem, making alternative Hedgehog modulators in high demand. Hhat is a membrane associated O-acyl transferase (MBOAT) whose only known function is the palmitoylation of Hedgehog, a posttranslational modification crucial for Hedgehog signalling. Targeting Hhat thus represents a uniquely specific way to target the hedgehog pathway that could be less prone to gaining resistance, but research in this area is hampered by a lack of good tool compounds. Here I propose to use cutting edge chemical biology tools to develop selective high potency Hhat inhibitors with thoroughly validated cellular activity. Such inhibitors are crucially needed to validate Hhat as a target in cancer therapy and the methodologies developed could be transferred to target other clinically relevant MBOATs in for example the Wnt pathway.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

See all projects funded under this funding scheme

Call for proposal

(opens in new window) H2020-MSCA-IF-2020

See all projects funded under this call

Coordinator

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Net EU contribution
€ 212 933,76
Address
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ London
United Kingdom
Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 212 933,76