UC Santa Cruz

Cancer is a deadly disease that affects 1 in 2 men and 1 in 3 women in the United States. The development of high throughput sequencing technologies has allowed for great advancements in cancer therapy, though, we still have a long way to go. Many cancer patients do not receive care soon enough due to late diagnosis, they do not receive the optimum treatment for their specific tumor type or they receive the optimum treatment, but then develop resistance to it. This thesis will address these three problems and describe how high throughput sequencing technology has allowed us to continue to make advancements in cancer treatment. Specifically, I will describe one example of how understanding the mechanism of oncogenesis can lead to new options for early diagnosis and monitoring of disease progression in about a quarter of glioblastoma multiforme and IDH wild-type lower grade glioma patients, harboring double minute chromosomes. I show how comprehensive characterization of lower grade glioma patients has lead to the discovery of a new, more accurate method of subtyping patients, which will allow for patients to receive more appropriate treatment for their specific tumor type. This is especially important for one subtype of lower grade glioma patients who have poor prognosis and appear very similar to glioblastoma multiforme patients, and therefore should receive similar treatment. I will also describe how development of HER2+ breast cancer cell lines that are resistant to the targeted therapy lapatinib, has led to greater understanding of a mutation-independent mechanism of drug resistance involving activation of the Notch pathway. Patients with a similar mechanism of resistance may benefit from treatment with Notch inhibitors, several of which are currently being tested in clinical trials. All of these findings display ways in which high throughput sequencing can be used to make advances in our understanding of cancer, ultimately moving towards better treatment for patients and better patient outcomes.