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Return to "Precision Medicine" and Cancer Overview

More on "Precision Medicine" and Cancer

"Precision Medicine" and Cancer

Leaders of NYP's Cancer Centers Discuss How This Emerging Field is Changing Cancer Treatment

NEW YORK (Sep 1, 2013)

Stephen G. Emerson, M.D., Ph.D., and Lewis C. Cantley, Ph.D.
Stephen G. Emerson, M.D., Ph.D.,
(left) and Lewis C. Cantley, Ph.D.

Since the first sequencing of the human genome was carried out in 2001, scientists and clinicians have been paving the way for a new concept in cancer treatment – precision medicine. With the development of computation tools capable of reading the genome more efficiently and new DNA sequencing that lowered the costs, precision medicine has been taking root in the scientific and medical communities. This approach targets treatment to very specific alterations or mutations that are seen in an individual's tumor.

"I think we are at the tipping point for breakthroughs in targeted therapy in which you develop drugs that hit the very gene, or gene product, that is driving the cancer," says Lewis C. Cantley, Ph.D., Director of the Weill Cornell Cancer Center at NewYork-Presbyterian/Weill Cornell Medical Center. "It has allowed us to divide cancers into smaller and smaller subgroups."

"The challenge is how do we change the testing of patient samples and how do we change the laboratories so that they test for the right things as new information comes along," notes Stephen G. Emerson, M.D., Ph.D., Director of the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center. "And then how do we integrate this into prevention, screening, diagnosis, and treatment. It's a very exciting time."

With Breast Cancer

According to Dr. Cantley, breast cancer is a very good example of precision medicine applied in one of the early stages of cancer treatment. "Twenty years ago everyone with breast cancer was treated in the same way," explains Dr. Cantley. "It was then noticed that certain subsets of breast cancers had high levels of an estrogen receptor. They were called estrogen-receptor positive breast cancers. So the logical approach was to try to block the estrogen from supporting the proliferation of cells in the breast. Selective estrogen-receptor response modulators, or SERMs, would accomplish this and block binding of the estrogen receptor. That turned out to be very effective in that subset of cancers; it's now the standard of care.

"Shortly after that discovery, another set of breast cancers was found to be HER2-positive and subsequently another drug, Herceptin®, was developed that targets that receptor," continues Dr. Cantley. "That drug has been remarkably effective when given with adjuvant therapy and also has become the prevailing therapy. The re-emergence of that cancer compared to before the drug was available has been reduced by about 80 percent. We can now say that we have a targeted therapy for the majority of breast cancers."

Really Exploring Mutations

"We are plumbing the depths of what genetic mutations in tumors actually cause the tumors, and, in some cases, which cause resistance to current chemotherapy," says Dr. Emerson. "There are a few cancers that are the result of only one mutation, including one type of leukemia, called CML, and a type of lymphoma, called Burkitt's lymphoma. Every other cancer is most likely caused by at least two mutations – probably more. If we're going to effect a cure, we will have to identify each of those mutations and then target them."

The additional layer of complexity, notes Dr. Emerson, is that there are mutations in our cells all of the time. "Most of these mutations don't matter because they are silent – they don't cause a change in the protein," explains Dr. Emerson. "So when you look at a tumor you have to distinguish those that matter from those that don't. Researchers are also identifying the right targets to try to kill the cancer while avoiding normal cells. What precision medicine should do is guide a patient's rational place in a clinical trial."

Current Research

NewYork-Presbyterian Hospital and its medical school affiliates have significant efforts underway devoted to doing just this. "It's not just about testing genes," says Dr. Emerson.

At Weill Cornell, Dr. Cantley – a proponent of team science – is developing an infrastructure for the Cancer Center that will facilitate the transition from identifying drug targets to science-based clinical trials. "In order to figure out how to use these new drugs, you need basic scientists, surgeons and clinicians, and molecular pathologists all working together as a team to identify the targets to go after and, importantly, to implement that into biomarker-driven clinical trials," says Dr. Cantley.

Under Dr. Emerson's direction, the Herbert Irving Comprehensive Cancer Center is expanding on its work with a goal to becoming the nexus of cancer prevention, treatment, and life-saving research. "Our scientists are pursuing basic discoveries in cancer biology that we will directly translate into improved treatments for our local patients, and patients throughout the nation and beyond," says Dr. Emerson. "To achieve these goals requires work on many levels, taking advantage of genetics and protein chemistry by using DNA, RNA, and protein sequencing to make personalized medicine a reality." In addition to leading NewYork-Presbyterian Hospital's cancer programs, Drs. Cantley and Emerson are pioneering researchers in their own right.

In applying precision medicine to his current work in lung cancer, Dr. Cantley follows two precepts: "Know your enemy," and, "Divide and conquer." "Once you understand the mechanisms in the various subsets of lung cancer, you can divide them into clinical trials based on what's happening in a patient's tumor," notes Dr. Cantley. "That's what we mean by precision and what we mean by targeted. It's a lot of work up front, but once we've solved it, we've solved it forever, making cancer only a nuisance disease for our grandchildren. That's my goal."

Dr. Emerson is pursuing research on what makes bone marrow blood stem cells grow into mature, functional blood cells. "We're investigating how they respond to signals that make them stop growing when cancer develops and how to fix that," says Dr. Emerson. "We don't have to understand the biology of every cell; we have to understand the biology of the one cell in a thousand that gives rise to new cells. Imagine not treating patients with toxic blasts of chemotherapy, but just picking out the stem cells that matter most with a magic bullet. It's a Copernican Revolution."

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