Synthesis of novel activators for procaspase-3: an approach to a personalised cancer treatment

Cancer is an important public health concern around the world. Chemotherapy is no doubt one of the most successful ways in which cancer can be treated. For years, chemotherapy has been indiscriminate warfare by using chemotherapeutic agents that are toxic to both normal and cancer cells. In this project we will design, prepare and evaluate molecules that are benign towards normal cells. Each individual has different levels of proteins in the body. If a personalized cancer treatment would become availabl e, this should reduce the need for different chemotherapeutic agents before finding one agent that works. This should offer advantages such as reduced treatment time, costs for society and reduce the many side-effects that cancer patients suffer. In thi s research project we develop molecules that should have potential as personalized cancer therapy. These small organic molecules activate the protein caspase-3. This protein is generated after activation of procaspase-3. The conversion of procaspase-3 to caspase-3 results in the generation of an executioner protein that induces cell death for the cancer cells. From a chemotherapeutic perspective, it is interesting and noteworthy that cells from certain types of cancerous tissues, such as colon, lung, mela noma, renal and breast cancers, contain elevated levels of procaspase-3. Hence, by measuring the level of procaspase-3 in patients before chemotherapy is initiated, treatment using a procaspase-3 activating drug will be given only to those patients that h ave elevated levels of procaspase-3. Hence, a personalized cancer strategy is achieved.