Grant: Travel Awards - Institute Community Support

ICS Travel Awards One third of childhood cancers are leukemias, with Acute Lymphoblastic Leukemia (ALL) accounting for 80% of childhood leukemias. Although improvements in chemotherapy have resulted in an 80% treatment success rate, acquired drug resistance remains a key obstacle to the treatment of the remaining 20%. Thus, new strategies that counter acquired drug resistance are urgently needed for the treatment of relapsed childhood leukemias. This proposal will investigate the causes contributing to acquired drug resistance in childhood ALL. Specifically, one involving cell adhesion termed Cell Adhesion Mediated Drug Resistance (CAMDR). Cell adhesion is the binding of a cell to cellular matter outside of the cell. This binding is known to trigger the tumor cell's ability to tolerate drugs that would normally kill it. We have shown that adhesion via cell adhesion protein named alpha4 integrins convey enhanced chemotherapeutic drug resistance in ALL cancer cells. We also show that a protein, calreticulin which normally acts as a storage unit for calcium inside the cell and a checker for proper protein production, is involved in CAMDR. Eliminating calreticulin from these drug resistant cells will make them susceptible to drugs again. We have also observed similar drug resistance phenomenon involving calreticulin in Medulloblastoma, a form of brain cancer that happens mostly in children. Continuing research will focus on pinpointing the exact role and function of calreticulin in the sequence of events following cell adhesion that leads to drug resistance. We will also investigate whether calreticulin involvement in chemoresistance is common across different types of cancer. We can capitalize on the findings of this project by blocking calreticulin function to reduce the chemoresistance of cancer cells in order to reduce chances of cancer relapse and use much less drug to minimize the harmful side effects of chemotherapy.