What is cancer?
Cancers come in many different types and forms in which uncontrolled cell growth can spread to other parts of the body. Despite remarkable advances in the past decades, cancer continues to be one of the leading causes of death worldwide.
The disease is caused by genetic changes or environmental effects that interfere with the mechanisms that control cell growth. These changes, as well as normal cell activities, can be detected in tissue or blood samples through the presence of their unique molecular indicators, called "markers" or "biomarkers." Specific combinations of these markers may be associated with a given type of cancer, indicating a person's susceptibility to developing a specific form of cancer and likelihood of responding to a specific treatment.
Role of genes and proteins
Most genes store the plans for how to construct a protein. Proteins are the primary building blocks and machinery of the cell. In normal life processes, the functions of genes, proteins and other molecules are activated and deactivated by other genes, proteins, regulatory molecules such as RNAs, or environmental factors such as temperature, radiation, foods or chemicals.
For any given function, there are often many factors that can increase or inhibit the function. Functions can range from whether a specific protein should be made or destroyed within the cell, to complex functions that trigger a cell to divide and grow into two cells. There is a very complicated interplay among all of the components in a cell. The factors controlling a function can range from the presence or lack of other proteins, chemicals, and other cellular signals. In normal cells these factors maintain a balance which results in the desired overall operation and health of individual cells and the whole organism. However, a defect or change in any of the components of a cell can upset the balance, which for cancer, leads to uncontrolled cell growth.
If a random event changes a gene, the corresponding protein may be constructed incorrectly and thus not able to perform its necessary function. For example, if that function was supposed to control cell growth, the cell could multiply without any inhibition and form a tumor. Some cancerous cells may spread to adjacent organs or travel in the blood stream to start growing in other parts of the body, causing further damage.
Identifying cancer markers
There are many approaches to treating cancer, but few are broadly applicable. Part of the problem is the diversity of types of cancers. In addition, an individual person's response to a treatment may differ from that of another individual. Further complicating matters, the cancerous cells can evolve unique defenses against specific treatments.
Detecting cancer early usually results in a significantly better treatment outcome. Unfortunately, many cancers are detected late due to lack of accurate diagnosis of early, subtle symptoms, resulting in poor patient outcomes. To address this, researchers focus on characterizing the differences in the activity of genes, proteins and other molecules between healthy and cancerous tissue samples, and between aggressive and less aggressive forms of cancer. These changes may provide signals that aid in earlier diagnosis and more accurate characterization of the type of tumor. For example, an increase in the activity (or expression) of a particular set of genes may signal an early stage of cancer development, or the presence of a specific protein in blood may indicate a patient's response or resistance to treatment. Different markers can be useful across a range of clinical applications, including diagnosis, prognosis, and treatment response for particular forms of cancer.
The pattern of markers can determine whether an individual is susceptible to developing a specific form of cancer, and may also predict the progression of the disease, helping to suggest the best treatment for a given individual. For example, two patients with the same form of cancer may have different outcomes and react differently to the same treatment, due to a having different genetic profiles. While several markers are already known to be associated with certain cancers, there are many more that need to be discovered, as cancer is highly heterogeneous. Researchers know that thousands of clinically useful markers exist, but they need to be identified among the astronomical number of possible combinations of molecular signals.
The Proposed Solution
In this project, researchers at the Princess Margaret Cancer Center in Toronto, Canada, are using World Community Grid to analyze a massive amount of data from tissue and blood samples of cancer patients and healthy controls to identify combinations of markers that play a role in the development, progression and treatment of various forms of cancers. Initially, the research will focus on lung and ovarian cancer, followed by prostate, pancreatic and breast cancers. The project is designed to accommodate additional cancers in the future.
Identifying all clinically useful markers would require thousands of patient samples and testing an astronomical number of marker combinations, which would be intractable even on World Community Grid. Instead, the researchers have developed software which uses heuristics (clever steps that reduce the enormous search space by focusing on the most relevant subsets of combinations) to greatly reduce the computational effort required to look for significant marker patterns. Even these software methods require a very large amount of computer processing power. By using World Community Grid, the researchers will use the Mapping Cancer Markers project to break down this overwhelming process into smaller, manageable tasks which can be performed by our volunteers' computing devices. World Community Grid therefore allows researchers to undertake this ambitious research.
Mapping Cancer Markers aims to improve and personalize cancer treatment. The project has three goals: first, to identify markers that can be used to detect cancer earlier; second, to identify high-risk cancer patients; and third, to find markers that can predict treatment response.
Mapping Cancer Markers will also enable researchers to develop even more efficient and effective computational methods for discovering relevant patterns of markers. This could help make the use of markers in personalized medicine more practical and more broadly applicable to other cancers and other complex diseases.