Improved Genetic Models for Non-small-cell Lung Cancer

Oliver and colleagues developed a genetic model of non-small-cell lung cancer (NSCLC)-squamous cell carcinoma and used the model to show how lineage-defining transcription factors such as Sox2 and NKX2-1 activate genes and pathways that determine different tumor immune microenvironments. Continue reading → Improved Genetic Models for Non-small-cell Lung Cancer

Defining Pathways for Formation and Suppression of Highly Metastatic Lung Tumors

Cancers arise from the complex interplay of oncogene activation and tumor suppressor inactivation. Oliver and colleagues uncovered how Myc cooperates with other oncogene products to promote aggressive, highly metastatic lung tumors. Continue reading → Defining Pathways for Formation and Suppression of Highly Metastatic Lung Tumors

Research Statement

The Oliver Lab focuses on mechanisms of drug response and resistance in lung cancer with the goal of improving treatment options for patients with lung cancer.

Lung Cancer: Two Major Subtypes

Lung cancer is the leading cause of cancer-related death in the United States and is divided into two major subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). More than 80% of lung cancer patients have NSCLC, which are typically adenocarcinoma, squamous cell carcinoma or large cell carcinoma.

These patients are usually treated with combination chemotherapy regimens including a platinum-based compound such as cisplatin. However, only about 30% of tumors respond to therapy and the five-year survival rate is only 15%.

Approximately 20% of patients have small cell lung cancer (SCLC). SCLC is highly responsive to platinum-based chemotherapy with ~80% response rate. However, tumors almost always acquire resistance, and there are currently no targeted therapies approved for these patients. Drug resistance, both inherent and acquired, is a major problem preventing effective lung cancer treatment.

Personalizing Cancer Therapies

The Oliver Lab is interested in understanding mechanisms of therapeutic response and resistance in order to personalize cancer therapies based on the characteristics of a given tumor. Our approach is to integrate human genomics/sequencing data with mechanistic data gleaned from cell culture systems and sophisticated mouse models of lung cancer.

We use mouse models of lung cancer that closely resemble human lung cancer. Genes that are altered in human lung cancer are altered by genetic engineering in mice, or by lentiviral delivery of genes specifically to the mouse lung. We use bacterial Cre/LoxP systems and CRISPR/Cas9 systems to alter cancer genes in living mice. To monitor the therapeutic response of mouse lung tumors, we use state-of-the-art imaging technologies (such as micro-CT and bioluminescent imaging). We also use mouse and human cancer cell lines to probe the function of particular genes and signaling pathways.

Other techniques used in the lab include genomics, single-cell sequencing technologies, biochemistry, molecular and cellular biology, lentiviral technologies and high-throughput drug screening. We have numerous collaborators in the United States and internationally, and we work with pharmaceutical companies to test novel therapies in our mouse models.

Oliver Lab