Precision Cancer Medicine
Medically reviewed by C. H. Weaver M. D., Medical Editor
Precision cancer medicine is an evolving concept in cancer care that aims to leverage new genomic information about a specific cancer to more precisely target treatment. Precision medicine seeks to define the genomic alterations that are driving a specific cancer, rather than relying on a simple broad classification of cancer solely based on its site of origin.
The idea of matching a particular treatment to a particular patient is not a new one. It has long been recognized, for example, that hormonal therapy for breast cancer is most likely to be effective when the breast cancer contains receptors for estrogen and/or progesterone. Testing for these receptors is part of the standard clinical work-up of breast cancer. What is new, however, is the pace at which researchers are identifying new tumor markers, new tests, and new and more targeted drugs that individualize cancer treatment. The purpose of precision cancer medicine is not to categorize or classify cancers solely by site of origin, but to define the genomic alterations in the cancers DNA that are driving that specific cancer.
Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
Not all cancer cells are alike
Cancer cells may differ from one another based on what genes have mutations. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. This “genomic testing” is performed on a biopsy sample of the cancer and increasingly in the blood using a “liquid biopsy”.
Genomic tests are used to identify the specific genes in a cancer that are abnormal or are not working properly. In essence, this is like identifying the genetic signature or fingerprint of a particular cancer. Genomic testing is different from genetic testing. Genetic tests are typically used to determine whether a healthy individual has an inherited trait (gene) that predisposes them to developing cancer. Genomic tests evaluate the genes in a sample of diseased tissue from a patient who has already been diagnosed with cancer. In this way, genes that have mutated, or have developed abnormal functions, are identified in addition to those that may have been inherited.
Once a genetic abnormality is identified, a specific precision cancer medicine or targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells.
Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
Precision cancer medicines can be used both instead of and in addition to chemotherapy to improve treatment outcomes.
Most or all cancers result from abnormal genes or gene regulation. The cause of these changes can be environmental, spontaneous, or inherited. By identifying the genomic changes and knowing which genes are altered in a patient, cancer drugs that specifically attack that gene (or the later consequences of that gene) can be used to target the cancer and avoid the more general side effects of chemotherapy.
Cancer occurs when good cells go bad. Normal cells in the body have complex control systems that allow them to replicate when the body is growing, or to replace damaged cells. When the damage to a cell cannot be fixed or when a cell reaches the end of its useful life span, the cell is programmed to die. This programmed cell death is a process called apoptosis. Cancer occurs when cells don’t follow this orderly, regulated process of growth, repair, and apoptosis.
Disruptions in orderly cell growth and repair may be caused by genetic mutations and chromosome alterations that regulate a cell’s behavior. Often there are several of these genomic abnormalities driving the cancer, but these can be different in cancers that otherwise seem to be the same. Two people with the same type of breast cancer, for example, may not respond to treatment in the same way if their cancers are caused by different combinations of mutations. Because the development and spread of every cancer is driven by a unique set of abnormalities in that individual cancer’s genetic makeup, the genetic makeup of each breast cancer may be unique and vary from patient to patient. In other words, all breast cancers are not the same, and they cannot be optimally treated using the same drug.
Answers to Frequently Asked Questions About Genomic Testing & Precision Cancer Medicine –What You Need to Know
Q: What is genomic testing?
A: Genomic testing looks at a group of genes and their varying levels of expression. This gene expression or activity can characterize how genes interact with one another and predict the behavior of certain tissues within the body. This is in contrast to genetic testing, which looks at a specific change within an individual chromosome or gene, often as part of an inheritable trait.
Q: What role does genomic testing play in a cancer diagnosis?
A: Genomic testing can provide information about a patient’s prognosis based on the gene expression within an individual’s cancer tissue and can often predict if certain therapy (chemotherapy or precision cancer medicines) will be of benefit.
Q: At what point in the diagnostic process does genomic testing occur?
A: Genomic testing can occur at any time after a tissue sample (biopsy or resection) of cancer has been acquired.
Q: What if tissue is not available to perform genomic testing?
A: There are two options: an additional biopsy can be performed if feasible or an individual can consider a “liquid biopsy” A liquid biopsy is performed by testing a sample of blood for the presence of circulating cancer cells, known as circulating tumor cells. Samples of blood obtained from a liquid biopsy can also be tested for cell-free tumor DNA (cfDNA), which are fragments of DNA shed by cancer cells into a patient’s bloodstream.
Q:What questions should I ask my healthcare team about genomic testing?
A: The following are the primary questions to ask your healthcare provider.
- Is genomic testing available for the type of cancer I have, to aid in determining my overall prognosis?
- Will the results of this testing have the potential to change your management of the cancer? Specifically:
- Will the test be able to tell me if certain therapies will be of benefit in my treatment?
- Have you had positive outcomes in using this testing with other patients?
- Is this testing covered by my insurance plan? (This type of testing can run in the thousands of dollars, though many plans cover the tests without an out-of-pocket expense.)
Q: Are there specific cancer types for which the role of genomic testing is especially significant?
A: Genomic testing is developing at a rapid pace. Established testing is particularly advanced in colon, lungand breast cancer where several precision cancer medicines have already been developed. Genomic testing is also increasingly playing an important role in individuals with rare cancers, cancer of unknown primary and those with widely metastatic disease.
Undergoing genomic testing that looks at expression across a wide variety of genes may identify certain genes that could potentially be a target for therapy that is otherwise not considered. A change to a precision cancer medicine would have the potential to markedly improve survival.
Impact of Precision Medicine on Clinical Trial Design
Historically, clinical trials enrolled patients with a single type of cancer, such as lung cancer. The treatment was administered to that group of patients, and the response to therapy was measured without assessing the genomic makeup of the cancer. Now, to evaluate precision medicine, clinical trial models are being revised because evaluating precision medicine requires measuring the genetic makeup of the cancer before beginning treatment. The new model, a so-called “basket” trial, enrolls patients with similar mutations, rather than simply the same type of cancer. Patients must be evaluated and enrolled early so that genotyping studies can be performed.
Further Reading and Other Resources