Zubarev, Roman – Overcoming Drug Resistance by complementary Agents (ODRA): development of a novel proteomics-based strategy

Bakgrund

Most cancer patients die not because of the primary tumour, but because that tumour becomes metastatic, attacking many different organs of the body. Why does cancer become metastatic? One of the reasons is the failure of chemotherapy. When the anticancer agent administered to the patient fails to kill all cancer cells in the primary tumour, some drug-resistant cells are left alive and start proliferating again. This happens because during the chemotherapy some of the cancer cells learn how to evade death due to poisoning by the drug, and thus become resistant to that drug. Overcoming this drug resistance is the main purpose of this project.

Beskrivning

We plan to overcome drug resistance in cancer cells by adding to the main anticancer compound another drug as a supplement. The added molecule does not necessarily have to be approved against cancer; it may be approved for treatment of other diseases. What is important is that this supplement drug will make the cancer cells less resistant to the main anticancer agent, and thus fewer (if any) cancer cells will survived such a combined treatment. We chose as target colon cancer, a common deadly cancer type, for which several drugs have been approved. For three of these drugs we will try to find complementary compounds.

Mål

We will take three colon cancer cell lines and make them more resistant to the three chosen drugs than the original cell population. Then we will study by sophisticated proteomics tools the difference between the sensitive and resistant cells and determine the molecular mechanism of resistance. The bioinformatics software driven by artificial intelligence will predict which compounds need to be added to overcome the drug resistance. We will test these compounds and if needed repeat the procedure. In the end we hope not only identify the complementary compounds, but also develop a useful procedure applicable to all cancer types and drugs.