Early research projects to sequence tumors in clinical settings are helping physicians and pathologists identify mutations that respond to specific therapeutic drugs

Step by step, progress is happening in the use of genome sequencing to advance personalized and precision medicine, with clinical laboratories and pathologists in the forefront of these developments. Much of this effort is focused on cancer and the sequencing of tumors.

One recent example comes from New York City, where the genomes of tumors of patients with unresponsive cancers were sequenced at the Institute for Precision Medicine at Weill Cornell and New York-Presbyterian Hospital Weill Cornell Medical Center. The outcomes of this effort demonstrates how the results of such testing can help patients who had not found an effective therapy to control their cancers.

Precision Medicine Offer Dramatic Results for Cancer Patients

The resulting study provides early evidence as to how precision medicine could transform cancer care. The team recruited 97 patients who had “exhausted every treatment available” according to Himisha Beltran, MD, the study’s lead author. The researchers performed whole exome sequencing on 154 tumors, and found an average of 16 mutations per patient.

Himisha Beltran, MD, lead author of the Weill Cornell/New York-Presbyterian Hospital study, believes the study “demonstrates the feasibility of doing an extensive molecular analysis within a short time frame in order to find potential therapies that had not been used before.” (Photo copyright: Damon Runyon Cancer Research Foundation.)

Himisha Beltran, MD, lead author of the Weill Cornell/New York-Presbyterian Hospital study, believes the study “demonstrates the feasibility of doing an extensive molecular analysis within a short time frame in order to find potential therapies that had not been used before.” (Photo copyright: Damon Runyon Cancer Research Foundation.)

Although the vast majority of those mutations require further study in order for scientists to understand their clinical significance, 114 of those mutations could either be treated immediately with available drugs or were treatable with therapies under development. The results were reviewed by a multidisciplinary board, which took into account the results of genome sequencing for each patient, as well as their medical histories and radiology reports. The board then generated individual treatment plans.

Giving Pathologists Useful New Diagnostic Capabilities

One patient experienced especially positive results: the “dramatic and durable remission” of an advanced bladder cancer. Such results are exciting for clinicians because they offer a glimpse of what is possible when treatment is so highly individualized.

Another notable effort in the field of precision medicine is that of the Center for Personalized Diagnostics (CPD), which is a “joint initiative between Penn Medicine’s Department of Pathology and Laboratory Medicine and the Abramson Cancer Center to support precision medicine at Penn.”

Mark Gettis, a lung cancer patient featured in a CPD video, describes how genomic sequencing meant that his stage IV lung cancer was treated with a drug therapy rather than the chemotherapy he immediately expected. “It’s amazing how everything is just healing,” said Gettis.

Unavailable Therapies and a Steep Learning Curve Present Challenges

Despite precision medicine’s promising future, there are issues for clinicians, researchers, and patients to overcome. Some of the therapies recommended by the reports and multidisciplinary boards are not yet available. For example, of the 97 patients in the Weill Cornell study, only 5% could follow the board’s recommendations, mostly because the therapies were either still in clinical trials or simply were not available.

Another issue is the learning curve for caregivers, clinicians, and others involved in the process. Such challenges, however, are typical for a field that is, by all accounts, still in its infancy. What is important for the pathology profession is how quickly clinical studies are published in peer-reviewed journals. It will take this evidence to encourage the Medicare program and private payers to make more informed coverage and reimbursement decisions.

On the other hand, it is tough to argue with the success stories associated with the use of gene sequencing in support of cancer care. Examples, such as the full recovery of the patient with bladder cancer in the Weill Cornell study, and that of Mark Gettis, the patient who experienced great results due to the tests done at CPD, are motivating both researchers and physicians to expand their knowledge of how to use these diagnostic tools.

—Dava Stewart

Related Information:

Precision Medicine Initiative

The National Institutes of Health Precision Medicine Goals 

The NIH Precision Medicine Initiative Cohort Program 

Weill Cornell Clinical Test

Patient Mark Gettis’ Story

Obama’s $215 Million Precision Medicine Initiative: Will Congress Fund It and Can It Advance Genetic Testing and the Value of Clinical Laboratory Services?

Weill Cornell and New York Presbyterian to Create New Precision Medicine Institute to Use Genome Sequencing to Individualize Cancer Treatment