Cancer is caused by genetic changes (errors), making every cancer unique. Nevertheless, cancers share features that allow them to be grouped into categories or “subtypes.” A tumor’s subtype strongly influences its behavior, including growth rate, likelihood of responding to one therapy versus another, and probability of relapse. Knowing each tumor’s subtype could thus help determine which therapy is best for a give a patient, a concept known as “Precision Medicine.” Currently, subtype can only be determined by in-depth sequencing of tumor tissue, and thus it is not routinely determined in clinical practice.
The goal of this proposal is to develop a rapid, non-invasive, and inexpensive way to determine tumor subtype from a blood test. This is called “liquid biopsy,” and it is playing an increasingly important role in cancer care. Because liquid biopsies are non-invasive (i.e. they do not require surgery or other procedures), samples can be obtained repeatedly over a course of therapy, allowing better clinical decisions to be made.
Colorectal cancer (CRC) is the second-leading cause of cancer death in the United States, where it has a disproportionately lethal effect on African-Americans. Recently, a consensus panel concluded that the disease has four major subtypes based on patterns of gene expression (which genes are “on” or “off” in the tumors). In this proposal, we will use these
definitions to perform subtyping from liquid biopsies. In the future, the approaches we will develop here will be applicable to all cancers, not just those affecting the colon and rectum.