New Models of Early Cancer Development

Background

Developing appropriate models for diseases such as cancer and Alzheimer’s disease is critical for dissecting their disease mechanisms.

While studies in complex animal models and immortalized cell lines (specific cell lines developed to grow continuously) provide important insights about cancer, these have not translated into full clinical success. Cancer therapies may work in animal models but not in clinical trials when treating patients. Standard models may only provide information on the state of the cancer based on what the model was derived from—lacking in an understanding of the early stages of cancer growth and how cancer cells decide their fate in response to different cellular signaling cues and expand their population.

Models of human cancer development are needed that would enrich our knowledge about early stages of cancer pathology and provide new insights to help in cancer prevention, biomarkers for early detection, and targets to develop precision medicine for individual patients that can halt further cancer development and save their lives.

Approach

With AFCR’s continuing support, highly accomplished researcher, Prof. Nancy Ip of The Hong Kong University of Science and Technology, is developing an alternative approach to studying cancer and other human maladies that may provide an understanding of the early stages of the disease process.

Her team will develop a model from a type of stem cell called ‘induced pluripotent stem cells’ (iPSCs). These cells which are developed in the laboratory have the two properties of stem cells: 1) iPSCs can grow and renew indefinitely in laboratory dishes (culture) and 2) iPSCs retain the capacity to differentiate into specific cell types (pluripotency). Using a standard cell line of human B lymphocytes or lymphoblastoid cells, the scientists will use advanced molecular biology techniques with molecular transforming factors that will reprogram the cells to become iPSCs. Growing the iPSCs in specific differentiation media will direct the cells to grow into different precursors of cancer cells and cell types of the body—the pluripotency.

Using the iPSCs, the scientists will focus on the amyloid precursor protein—which is involved in Alzheimer’s disease and, is also abnormally expressed in pancreatic, colon, breast, prostate, lung and other cancers. This protein has recently been shown to have a significant correlation with increased cancer cell proliferation and the migration of cancer cells from the tumor and invasion into healthy tissue.

Prof. Ip’s team will use genome editing technology to edit the amyloid precursor protein gene in iPSC lines. These isogenic cell lines will allow them to study the pathological mechanisms of early stages of cancer by regulating the abnormal expression of the amyloid precursor protein.

Impact

Using the sophisticated technique of generating iPSCs, Prof. Ip will explore a new approach that may allow insights into how cancer develops from cells with the abnormal expression of the 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.
iPSCs derived from a patient’s tumor cells can be a new model to add to the growing number of patient-derived models in which individual therapeutics can be assessed.

With iPSCs, potential biomarkers to detect early-stage cancer can be identified. The contribution of gene candidates to cancer and in precision medicine can be assessed.