Understanding Precision Cancer Medicine

Posted on August 25th, 2015 by

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.

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.

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 drugs.

Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. By defining the consequences of these genetic abnormalities doctors can identify specific treatments directed against each genetic abnormality for each individual patient’s unique DNA profile.

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 cells. Standard chemotherapy typically destroys both normal and cancerous rapidly dividing cells in a wide range of tissues, often causing side effects by damaging normal cells. Precision cancer medicine uses targeted therapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

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.

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