Identification of Genetic Pathways that Regulate the Survival and Development of Cancer and Cancer Stem Cells
The Problem: Cancers include a small number of cancer stem cells (CSCs) that drive the disease.
Effective therapies for cancer patients require a thorough understanding of mechanisms leading to tumor development and drug resistance. Breast cancer, leukemia and brain tumors are among the most common and lethal tumors that affect Canadians of all ages, imposing a huge social and economic burden. Because these cancers frequently affect young women and children, many patients are given very aggressive treatments to improve their chances of survival. Unfortunately, these treatments often have serious side effects, especially in children, because they can harm a broad range of normal cells. Moreover, conventional treatments are often not effective in fighting the most serious forms of these cancers.
Recent findings suggest that these tumors are derived from cancer stem cells (CSCs) that function as the "root" of the tumor. CSCs are rare, representing approximately one in a million cells within a tumor, and their biological properties are often very different than the major tumor cell population. Therefore, we aim to identify CSCs and define their biological properties so that we can develop "smart bomb" approaches to treating the roots of these cancers. This new approach can improve cancer therapy and reduce harmful side effects. However, the rare numbers of CSCs also pose a challenge to researchers who have to constantly work with needles in haystacks of cells.
Figure 1: Strategies for the identification and characterization of Cancer Stem Cells
The Solution: Characterize Molecular Networks in Cancer Stem Cells.
The project team hopes that their research will eventually increase survival rates and improve quality of life for survivors of breast cancer, leukemia and brain tumors. To accomplish this goal we have assembled an interdisciplinary group to address the significant challenge of identifying and characterizing molecular networks that control CSCs.
In particular, investigators will seek to determine what genetic alterations distinguish very aggressive from more benign tumors, and what genetic and biological malfunctions lead to the development of CSCs. By dissecting the cellular signals that govern abnormal survival of tumor cells and CSCs, the project is expected to develop new "biomarkers" that may help to reserve the most aggressive cancer treatments for patients with the highest risk of failing conventional therapies. Ultimately, the project may lead to development of new and more effective therapies specifically targeted to CSCs.