The aim of LIGHTS is the discovery of "Small ligands to interfere
with Thymidylate synthase dimer formation as new tools for development of
anticancer agents against ovarian carcinoma". 
Thymidylate synthase (TS) is an enzyme that plays an essential role in DNA synthesis and cell proliferation. TS inhibitors are used as anti-cancer drugs. Ovarian cancer is the
fifth most common cause of death from cancer in women. The standard treatment is with platinum drugs. After some time, the cancer cells become
resistant to these drugs and cross-resistance to TS inhibitors accompanied by an increase in TS protein levels is observed. The goal of LIGHTS is to halt tumour progression and the development of drug resistance upon treatment with platinum-derived drugs by inhibiting the protein regulatory function of monomeric thymidylate synthase. Libraries of small molecules will be designed to interfere with dimerization of TS. In contrast to known TS inhibitors, which bind in the active site, these compounds will be targeted at a protein-protein interface. The disruption of protein-protein interfaces by the design of small molecules is challenging and therefore, a multipronged strategy, including protein tethering to identify low-affinity ligands and design of peptide mimetics, will be followed.
The LIGHTS project is being carried out by a consortium of six partners from five countries. A multidisciplinary approach is being taken, integrating molecular modelling, chemoinformatics, synthetic chemistry, molecular biology, structural biology and pharmacology.
The LIGHTS project is supported by the EU in the 6th Framework Program as an 'SME (small-medium size enterprise) dedicated STREP (specific targeted research or innovation project)'.
For more information, see: www.lights-eu.org.
