Cell signaling in cancer, drug treatment and resistance
Posttranslational modifications (PTMs) are known to modulate enzyme activity, affect sub-cellular localization and trafficking, influence half-life of proteins and regulate molecular interactions. They render the possibility to respond flexibly and rapidly to varying extra- and intracellular cues and change protein and thus cell function without the need to change protein expression. As aberrant function of enzymes that regulate PTM abundance (like protein kinases) leads to disturbed signaling and is often associated with proliferative diseases like cancer, these enzymes are prime targets for the design of small molecule inhibitors and therapeutic proteins. Although many of these drugs have shown promising results in clinics, resistance often inevitably occurs.
This illustrates the need for a better understanding of the dynamics of phosphorylation and other posttranslational modifications in different disease, treatment and resistance settings. We aim to map differences of PTM levels between various cancer cell lines, clarify the molecular mode of action of different cancer drugs, spot potential novel drug targets, elucidate resistance mechanisms, and identify new signaling biomarkers.