PRECISION MEDICINE: WHAT IT MEANS NOW. WHAT IT MEANS FOR THE FUTURE

August 25, 2015 | by Veronique de Turenne

It was 2009 when a City of Hope patient in her 40s learned that the cancer she had been fighting for several years had metastasized to her lungs. Her medical team ran genetic tests on the tumor, but none of the drug therapies available at the time targeted the known mutations in the tumor cells.

Although at first the woman responded to chemotherapy, by 2013 toxicity had caused side effects so grave that the patient was faced with stopping her treatment. And then her doctors ran another test.

It was 2009 when a City of Hope patient in her 40s learned that the cancer she had been fighting for several years had metastasized to her lungs. Her medical team ran genetic tests on the tumor, but none of the drug therapies available at the time targeted the known mutations in the tumor cells.

Although at first the woman responded to chemotherapy, by 2013 toxicity had caused side effects so grave that the patient was faced with stopping her treatment. And then her doctors ran another test.

karen reckamp 256x256 Karen Reckamp, M.D.

“We re-tested the biology of the tumor and this time, it turned out that we knew so much more about it,” said Karen Reckamp, M.D., medical director for Clinical Research Operations at City of Hope. Just four years after that initial diagnosis, doctors were able to identify a genetic mutation that previously had gone unrecognized. The best news of all – a drug that acted against that specific mutation was now available.

“She has been on the new treatment for two years now, with very good success,” said Reckamp, also co-chair of the Lung Cancer and Thoracic Oncology Program at City of Hope. “That’s one of my favorite stories.”

Welcome to the brave new world of precision medicine, in which the diseases themselves can point to a treatment and even a cure. What was once dismissed as futuristic has now become reality for some cancer patients, and with leading-edge research and groundbreaking partnerships, City of Hope stands in the precision medicine vanguard.

Rosen-Steven Steven T. Rosen, M.D.

“Precision medicine is the future of cancer care,” said Steven T. Rosen, M.D., provost and chief scientific officer at City of Hope. “We have been evolving toward a personalized approach to the treatment of cancer for a number of years, and as we continue to develop insight into targeted treatment, I see us becoming ever more precise in how we select and administer therapies.”

Where DNA, tumor genomes and lifestyle combine

So what is precision medicine? It’s an emerging medical model that takes into account the unique genetic code of each individual, and then compares it to the genome of that person’s tumor. Doctors also factor in environmental and lifestyle influences, such as smoking or exposure to toxins, which can affect cancer development, and then propose treatment options that are specifically targeted to each patient. The approach has such promise that, during his State of the Union address at the start of this year, President Barack Obama announced a Precision Medicine Initiative, along with $215 million in initial funding.

Decades of research have revealed that cancer is fundamentally a disease of the genome. What makes cancer cells different from normal cells are the changes in their genes, which cause them to grow and divide at a rate that wreaks havoc on the human body. Yet it is these very changes that make cancer uniquely suited to precision medicine, said

Sumanta Pal 256x256 Sumanta Kumar Pal, M.D.

Sumanta Kumar Pal, M.D., an assistant clinical professor in the Department of Medical Oncology and Therapeutics Research, and co-director of the Kidney Cancer Program at City of Hope. By first mapping an individual’s genome, and then mapping the genome of his or her tumor, doctors can clearly see the mutations that are driving the cancer, and thus work to develop a targeted therapy.

“We’ve suspected for some time that every cancer has a unique biology,” Pal said. “What we lacked was the technology to identify the relevant genes.”

The turning point came in 2003 with the completion of the Human Genome Project, an international scientific collaboration that resulted in the first-ever complete genetic map of human DNA. In the time since the completion of the Human Genome Project, technology has grown apace. The first human genome took eight years and close to $1 billion dollars to complete. Now, a genome can be sequenced in mere days, and for just a few thousand dollars.

For patients with bladder cancer, a disease with limited treatment options, advances in precision medicine have had dramatic results.

“A gentleman with bladder cancer who I was treating had progressed beyond the first-line chemo regimen and was at the point where hospice was the only option,” Pal said. “We ordered a genetic profile and when we found a mutation (in the FGFR3 gene), we were able to enroll him in a clinical trial of an agent that specifically targets that mutation.”

New challenges in this new world

With each advance, however, comes a new set of challenges. The most pressing is the need to collect adequate data to create a knowledge pool that is both deep enough and sufficiently diverse to yield reliable answers. Then, with such an avalanche of information, comes the need for the tools toquickly make sense of it all.

“You need hundreds of thousands of patients to gather the information that’s critical to being able to conduct studies and trials that will provide answers,” Pal said, adding: “We’re in this era of big data, and part of the challenge is to associate these various factors with precise information regarding ethnicity, socio-economic background, genetic makeup.”

To that end, City of Hope has recently entered into a trio of partnerships to collect, organize, and evaluate the vast pool of patient data necessary for the advancement of precision medicine.

The first, the Oncology Research Information Exchange Network, also known as ORIEN, is the largest collaboration for cancer research ever assembled. ORIEN, which launches with clinical data from more than 100,000 patients who have donated both tissue and clinical data for cancer research at the molecular level, will speed advances in the development of precision medicine treatments.

In July, doctors at City of Hope joined a new National Cancer Institute clinical trial called NCI-Molecular Analysis for Therapy Choice. Also known as NCI-MATCH, the trial will analyze patients’ tumors in order to determine whether they contain genetic abnormalities for which targeted therapies already exist. Reckamp, who will serve as a principal investigator for one of the arms of the multicenter trial, said the trial will give patients with rare cancers much greater access to targeted therapies.

Larry Kwak - 256x256 Larry W. Kwak, M.D., Ph.D.

Because the nature of cancer research is dealing with a deluge of information – the genome of just one patient totals more than 100 gigabytes -- partnerships such as these are the key to future breakthroughs, said Larry W. Kwak, M.D., Ph.D., Cancer Center Associate Director for Translational Research and Developmental Therapeutics.

Data, data and more data

“Access to large groups of patients is crucial to being able to do significant research,” Kwak said. “Because the mutations (that drive cancer) are rarely common to all cases, you need the largest group of patients possible, with detailed information tied to their clinical outcomes, to determine which mutations are significant, which are silent, or which are tied to barriers to effective treatment like drug resistance.”

Even with alliances such as ORIEN and NCI-MATCH joining in the fight, challenges to the future of precision medicine remain. At present, many of the tissue samples collected during the diagnostic process at smaller hospitals and medical centers are either not large enough, or are improperly stored, and are thus not suitable for gene sequencing.

Still, the pace of recent progress has doctors at City of Hope looking with confidence into the future.

“I believe we’re on the verge of new diagnostic tools, such as biomarker testing for cancer in tissue or in urine or even in the blood –  what you’d call a liquid biopsy,” said Reckamp, the Lung Cancer and Thoracic Oncology Program’s co-chair. She added:

“At City of Hope we are looking to provide specific treatments for a person’s specific cancer, and each year we are getting better and better at achieving that goal.”

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