Deciphering non-genetic mechanisms of response or resistance to treatment
Advances in cancer genomics have enabled the application of personalized medicine approaches based on a patient’s tumor genetics. However, non-genetic mechanisms are an important contributor to the diverse functional phenotypes in cancer cells, which can influence treatment response. These heterogeneous sub-populations can also arise in response to treatment by acquiring mechanisms to circumvent the damaging effects of therapy, eventually leading to relapse. Such sub-populations are difficult to analyze using bulk methods. We aim to understand the heterogeneous transcriptome of primary and metastatic colorectal (CRC) tumors by using single-cell RNA sequencing (scRNA-seq) to identify relevant treatment targets. Additionally, we will use scRNA-seq to identify mechanisms of adaptive resistance to chemotherapy and target therapy in various CRC models including cell lines, organoids and patient derived models. Identification of these mechanisms will be used to develop rational combination treatment strategies to potentially circumvent the emergence of resistant populations.