Carla Kim, Ph.D.

Institution: Children's Hospital Boston

Project: Using “Organoid” Model of Lung Cancer to Test Treatment

Grant(s): Lung Cancer Discovery Award

With advances in screening high-risk patients, more early-stage lung lesions are being identified. Unfortunately, physicians do not know how to recognize which lesions will develop into lung cancer or how to treat early-stage tumors. We will use an organoid model to understand genetic changes that transform a normal cell into a cancer cell in the lung. Organoids are 3-D cultures derived from stem cells. In these studies, lung stem cells that can become different types of cells in the lung will be used. These stem cells follow their own genetic instructions in the lab dish to organize themselves into tiny structures that resemble miniature organs. We will use 3-D organoid cultures to model the earliest stages of lung cancer. This organoid system has the potential to reduce lengthy periods of trial-and-error testing of treatments in patients. Shedding light on early changes in tumor cells will lead to a better understanding of lung cancer biology, and will help identify new targets for cancer prevention and treatment.

Update:

Non small cell lung cancer begins in the epithelial cells. The mutant KRAS gene is a common driver in epithelial cancers. Nevertheless, molecular changes occurring early after activation of cancer-causing KRAS in epithelial cells remain poorly understood. We developed an organoid system to rapidly model early-stage lung adenocarcinoma in the lab using primary lung alveolar epithelial progenitor cells. Our findings demonstrate the utility of our organoid approach for uncovering the early consequences of KRAS expression that leads to cancer, facilitating the search for targets for KRAS-driven tumors. Future studies will focus on understanding the role of stromal (connective tissue) cells in lung adenocarcinoma initiation and progression.

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