Years of AFCR Funding: 2014 to 2019
Models from stem cells – new approaches to stop cancer in its tracks
Nancy Ip, Ph.D.
The Hong Kong University of Science and Technology
Development of appropriate models for ailments such as cancer is a critically useful component to understanding disease pathogenesis. While studies in complex animal models and cell lines provide important insights, these commonly do not translate into clinical success. Cancer therapies effective in animal models often fall short when used to treat human patients.
Models of cancer development and progression continue to be refined, a process which too can lead to more effective diagnostic, preventive and treatment tools. Despite progress, still lacking is a full understanding of the earliest stages of cancer growth and how tumorous cells respond to different signaling cues.
With AFCR’s continuing support, Dr. Nancy Ip, a widely respected expert in both the cancer and Alzheimer’s disease fields, is developing a new model from a particular type of stem cell: induced pluripotent stem cells (iPSCs). This research may enrich our knowledge about early stages of cancer pathology and provide new insights which impact cancer prevention, help identify biomarkers for early detection and aid in the revelation of targets susceptible to precision medicine for patients.
iPSCs are available from standard tissue banks and can also be developed in the laboratory. They have two essential properties: (1) iPSCs can grow and renew indefinitely in laboratory dishes or cultures; and (2) iPSCs retain the capacity to differentiate into specific cell types (the feature known as pluripotency).
Employing a standard cell line of human B lymphocytes or lymphoblastoid cells, Dr. Ip’s team uses advanced molecular biology techniques to first reprogram the cells into becoming iPSCs. By growing the iPSCs in specific differentiation media, efforts are then directed into growing them into different precursor cancer cells and cell types of the body—a demonstration of pluripotency.
Using iPSCs, Dr. Ip’s team is focusing on the role of amyloid precursor protein (APP) in early stages of cancer. APP is abnormally expressed in pancreatic, colon, breast, prostate, lung and other cancers, and recent reports show it correlates significantly with increased cancer cell proliferation and the migration and invasion of cancer cells into healthy tissue.
Using the cutting-edge genome editing technology, CRISPR, Dr. Ip and her colleagues can generate various isogenic iPSC lines containing different doses of APP. By regulating the abnormal expression of APP in these isogenic cell lines, the scientists aim to identify and study the functions of APP in cancer development. Moreover, the researchers are establishing two and three-dimensional cultures from the iPSCs for disease mechanism studies.
With iPSCs, Dr. Ip is exploring a new model that may yield insights into how cancer develops from cells abnormally expressing amyloid precursor protein. With this new type of model, it may be possible to discover how these cancer cells respond to environmental cues in early events in cancer development. With iPSCs, potential biomarkers to detect early-stage cancer can be identified and the contribution of gene candidates to cancer and in precision medicine can be assessed. Moreover, iPSCs, subsequently engineered, hold promise as a treatment paradigm, adding to the growing number of means by which individual cancer therapies are developed.