Doctors today are shifting toward treating disease in a personalized way: by looking at a patient’s genes. This practice is allowing medical professionals and scientists to select a drug that is custom fit to the specific type of disease, specifically in the field of oncology.
A new study published in the Pancreas journal found evidence that assessing the route to cancer on a case-by-case basis might make more sense than basing a patient’s cancer treatment on commonly disrupted genes and pathways. John McDonald, a professor at the Georgia Institute of Technology in Atlanta said, “treat[ing] each person by looking for the etiology of the disease in patients individually… have ramifications on how we might best optimize cancer treatment.” This type of treatment rallies for individualism in medicine and zeroes-in on the root of the problem.
McDonald’s team of scientists at the Georgia Institute of Technology showed the effectiveness of personalized treatment by isolating cancer tissues from a set of patients relative to adjacent normal pancreatic tissue. The study found that 287 genes displayed significant differences in expression in the cancers versus normal tissues. Twenty-two cellular pathways were enriched in cancer samples, with more than half related to the body’s immune response. The researchers found that the molecular profile of each individual cancer patient was unique in terms of the most significantly disrupted genes and pathways.
“If you’re dealing with a disease like cancer that can be arrived at by multiple pathways, it makes sense that you’re not going to find that each patient has taken the same path,” McDonald said. Although the researchers noticed that there were some genes that were disrupted in all or most of the patients examined, these genes were not among the most significantly disrupted in any individual patient. “By and large, there appears to be a lot of individuality in terms of the molecular basis of pancreatic cancer,” said McDonald, who is also director of the Integrated Cancer Research Center and as the chief scientific officer of the Ovarian Cancer Institute.
Although the study size of McDonald’s research was relatively small, it definitely highlights the validity of targeting the most important gene or pathway underlying a disease by pooling data from multiple patients. McDonald maintains that individual profiling is the preferred method for initiating treatment.
Individual profiling for cancer patients’ allows scientists to identify and attack cancer cells using biomarkers and then develop drug agents directed at a person’s genetic mutations. These drugs attack cancer in distinct way; from cutting off a tumor’s blood supply, to initiating apoptosis (cell death), to restarting the immune system. But because cancer is not caused by a single agent, it is complex and can take on many forms. Cancer can be caused by thousands of distinctive biological switches, creating a broad range of cancer types and allowing for differences even within one type of cancer. Personalized cancer treatment may be extremely beneficial, where each person’s cancer is treated on an individual basis.
Traditionally. patients with the same stage and type of cancer have been given standard treatments. Yet these treatments worked for some patients, but not for others because of genetic differences in their tumors. And this is why oncologists are tuning to personalized treatment. Joan Scott, the deputy director of the Genetic and Public Policy Center of Washington D.C., stated, “Oncology is absolutely farther down this road of personalized medicine than other areas.”
With personalized cancer treatment, the patient’s tumor is biopsied and scanned for abnormal genes. Recently, treatments for particular gene mutations have become accessible. Patients can order the molecular testing of their tumors to determine their genetic profiles. After analyzing the genetic tests, doctors can make the prevention, screening, and treatment process for each patient more customized and effective, and minimize the side effects. Pathologist John Iafrate of Massachusetts General Hospital declared, “In the next few years, I think every major cancer center is going to work on this approach.
Some examples of personalized cancer treatment are targeted treatments and pharmacogenomics. Targeted treatments are directed to the exact genes and proteins of the cancer that allow for its growth and survival. Pharmacogenomics is involved in analyzing the relationship between a person’s genes and how he/she responds to drugs, and in this are involved in dosage selection. For example, epidermal-growth-factor-receptor gene mutations can influence patient response to drug treatment. This is particularly important for cancer medications which can be either life threatening or ineffective if given at the wrong dosage.
Furthermore, a group in Vancouver studied personalized treatment by sequencing an entire tumor, and comparing it to the genes of healthy cells. The patient, they discovered, had mutations in the PTEN gene, one of the key tumor suppressor genes, and extremely high expression of RET, which is involved in extracellular cell signaling. Because of the data they found, they moved him from the drugs he was taking to another drug, and afterwards the cancer successfully regressed.
Even with all the promising studies and data, there are major setbacks to personalized treatment. Genetic testing can be expensive (insurance plans often do not cover the cost) and lengthy. The cost of a molecular profiling analysis to transcribe the DNA sequences of exons — the parts of the genome that are translated into proteins — is about $2,000 (exons account for about two percent of a cell’s total DNA). While the cost has been reduced by half within the past five years, it is still burdensome. Moreover, scientists and doctors will have to shift their paradigm on how they use molecular profiling to treat cancer. For example, for any given individual patient there may be mutant genes or aberrant expression patterns that are vitally important for that person’s cancer that aren’t present in other patients’ cancers. Additionally, only a small number of drugs can be chosen to fit particular mutations and cancer types as new cancer types- like ovarian and lung cancer- begin to be studied.
Clearly, we still do not know everything there is to know about cancer and how to treat it. But we are well on our way to understanding the unique genetic and molecular pathways that are corrupted in people with cancer. Thanks to personalized cancer treatment, scientists definitely have a great lead. It’s time to face our fears and confront cancer, up close and personal.