Many cancers are fueled by biochemical changes of histones, the proteins that serve as spools for DNA in our cells (histones are shown in green with their cancer-induced changes in purple). New epigenetic therapies that reverse these changes are showing early promise in clinical trials.
Although the history of attempts to understand and control cancer is littered with disappointments, many significant advances in research and treatment have been made in recent years. Despite the challenges, Memorial Sloan Kettering scientists and doctors firmly believe we’re on the cusp of a brighter era in cancer care and research. Today, we have more reasons than ever to be hopeful. These are five of them.
Precision Medicine: Interpreting the Story of Genes
During his final State of the Union address in January, President Barack Obama announced an initiative focused on precision medicine — the vision that one day, all people will be offered customized care, with treatments that match our genetics and personal histories. Such individualized therapies promise to be more effective and cause fewer side effects than more traditional ones developed for the average patient.
Basket Trials
We have yet to realize the full potential of precision medicine, but we are making significant headway. Options for many people with cancer have dramatically improved through targeted therapies that reverse the effects of specific gene mutations in their tumor cells.
MSK scientists are working relentlessly to extend the promise of precision medicine to people with all kinds of cancer, both common and rare. Our pathologists — experts in diagnosing disease — are using a powerful tumor DNA sequencing test called MSK-IMPACT™ to guide therapy for patients with advanced disease, regardless of their tumor type.
In addition, MSK investigators are developing new research approaches and perfecting basket trials — a method of conducting clinical studies in which patients can enroll based on the mutations in their tumors — to help doctors deliver precision-medicine options to more patients, more quickly.
Checkpoint Inhibitors: Triggering Immune Defense
Using a patient’s own immune system to fight his or her cancer, known as immunotherapy, is the fruition of a century-old idea. MSK researchers have played a major role in the development of nivolumab and ipilimumab, two drugs that boost the cancer-fighting powers of the immune system’s T cells. These two drugs belong to a class of immunotherapy treatments called checkpoint inhibitors, which work by easing constraints on the immune system and thus helping it work better. So far both have produced remarkable results, eliminating cancer completely in some patients with highly advanced melanoma. Nivolumab is additionally approved for lung and kidney cancer, and another drug, pembrolizumab, is approved for lung cancer. Checkpoint inhibitors are also showing promise in bladder, head and neck, triple-negative breast, and other cancers.
These therapies don’t yet work in everyone, but scientists are making incredible strides in changing that. Recent MSK research has yielded important clues about how these drugs work and how they could be improved. In addition, MSK was recently named a founding member of the Parker Institute for Cancer Immunotherapy, which, thanks to a generous $250 million donation from tech entrepreneur Sean Parker, will hasten the study and implementation of new immunotherapy drugs.
Jedd Wolchok, Chief of the Melanoma Service at MSK, told Reuters that the new center “is paradigm shifting.”
“I have no doubt this will allow us to make progress, and to make it much more quickly,” he said.
Cell-Based Therapy: “Living Drugs” to Better Fight Cancer
In addition to drugs such as ipilimumab and nivolumab, MSK researchers are developing another immunotherapy strategy in which a patient’s own T cells are manipulated to more readily attack cancer cells. In this treatment, called chimeric antigen receptor therapy, or CAR therapy, T cells are collected from a patient’s blood, genetically engineered to recognize certain proteins on cancer cells, and infused back into the patient’s bloodstream.
The approach is showing early promise for relapsed B cell acute lymphoblastic leukemia and some other blood cancers, and might potentially be useful for treating solid tumors as well.
“We’re creating living drugs,” Michel Sadelain, a pioneer in the field and Director of MSK’s Center for Cell Engineering, told the New York Times about CAR therapy. The concept of these drugs — therapies in which live cells are either infused or transplanted into patients — is exciting because cells are presumably more nimble than chemicals or biological compounds. For example, they can sense multiple cues from their environment and appropriately respond.
For most of these cell-based treatments, scientists are still working to ensure their safety or manage their side effects.
Epigenetic Therapy: Setting Cancer Cells Straight
Epigenetics
Doctors have long searched for ways to control cancer by cutting out tumors or poisoning them with chemicals and radiation. But what if cancer could be treated in a different way, by transforming cancer cells back to normal rather than destroying them?
Research into epigenetics — how genes can switch “on” or “off” depending on outside influences — is changing our understanding of cancer and many other diseases. It has also led to the development of a number of new drugs in clinical trials at MSK. All of them target epigenetic enzymes, which regulate a cell’s genetic programming. Rather than destroy cancer cells, the therapies seek to set the cells on a path back toward normal growth and development.
One such drug, called AG-221, is being tested in people with acute myeloid leukemia (AML) and myelodysplastic syndromes. As of September 2015, the drug had a 38% response rate in 159 patients whose AML had returned and been resistant to treatment. Similar results have been seen with some other new blood cancer drugs.
Research into Metastasis: Unmasking the Latent Enemy
For almost 200 years, scientists have been toiling to understand metastasis, the process that allows some cancer cells to break off from their tumor of origin and take root in a different tissue. Today, the problem is as urgent as ever. Metastasis causes nine out of ten deaths from cancer, and survival rates haven’t improved much since the 1960s.
The process has been challenging to study and control for many reasons. One is that metastatic tumor cells are very rare in the body compared with the millions of tumor cells that don’t cause metastasis, and they’re therefore hard to detect and isolate.
But the tide is finally turning. In recent years, scientists have identified genes and pathways that commonly drive the spread of breast cancer or neuroblastoma to the brain and kidney cancer metastasis to various organs. In 2014, our scientists discovered that metastatic tumor cells have a remarkable tendency to cling to blood vessels, a survival mechanism that might be important for the spread of many types of cancer. Our researchers have also shed light on how cancer cells hide out and remain undetected by our immune system, opening up a promising new avenue for treatment.
Scientists are also finding that tumors can hijack normal cells and tissues growing in their neighborhood and coax them into supporting cancer spread. To counter that, our researchers have discovered that drugs that act on a specific type of blood cell can slow breast-to-brain metastasis or block the progression of glioblastoma brain tumors in mice.
The more we learn about metastasis, the more likely we are to see new treatment options emerge. “Mankind is turning cancer from what we’ve known it to be — the way we’ve related to it in the 20th century as an impossible, obscure disease — into a ‘normalized’ disease,” Joan Massagué, Director of the Sloan Kettering Institute and a prominent metastasis researcher, said in an interview. “Our relationship with it will be much more like the one we have with infectious diseases, for which we have antibiotics and other treatments.”
