News

February 18, 2019

Why Some Brain Tumors Respond to Immunotherapy

Columbia researchers have learned why some glioblastomas—the most common type of brain cancer—respond to immunotherapy. The findings, reported by the CUIMC Newsroom, could help identify patients who are most likely to benefit from treatment with immunotherapy drugs and lead to the development of more broadly effective treatments.

The study, led by Raul Rabadan, PhD, professor of systems biology and biomedical informatics at Columbia University Vagelos College of Physicians and Surgeons and the Herbert Irving Comprehensive Cancer Center, was published online in the journal Nature Medicine. 

Fewer than 1 in 10 patients with glioblastoma­ respond to immunotherapy, which has shown remarkable success in the past few years in treating a variety of aggressive cancers. But there has been no way to know in advance which glioblastoma patients will respond. Like many other cancers, glioblastomas are able to prevent the immune system from attacking cancer cells. Cancers sometimes put the brakes on the immune system by acting on a protein called PD-1. Immunotherapy drugs called PD-1 inhibitors are designed to release those brakes, unleashing the immune system. Given the success of PD-1 inhibitors in other cancers, doctors were hopeful that the immunotherapy drugs would help patients with glioblastoma. 

To understand why only a few of these tumors respond to the immunotherapy drugs, Dr. Rabadan’s team took a comprehensive look at the tumor microenvironment—which includes the tumor itself and all of the cells that support it—in 66 glioblastoma patients before and after treatment with PD-1 inhibitors (nivolumab or pembrolizumab). Of these, 17 had a response to the drugs of six months or longer.

Nonresponsive tumors had more mutations in a gene called PTEN, which led to higher levels of macrophages, immune cells that usually help the body fight bacteria and other invaders. But in glioblastoma, the macrophages release a number of growth factors that promote the survival and spread of cancer cells.

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January 22, 2019

Prostate Cancer Grant Spotlights Columbia’s Aim to Deliver Precision Cancer Medicine

 

PCF Challenge Award PIs
Principal investigators on the PCF Challenge Award grant, from left to right: Andrea Califano, Michael Shen and Charles Drake.

Columbia University Irving Medical Center experts in prostate cancer will lead a new team research project that tests a novel approach for personalized cancer treatment. 

The two-year project, funded by a $1 million Challenge Award from the Prostate Cancer Foundation (PCF) , combines cutting-edge techniques that include computational methods for targeted drug therapy, single-cell RNA sequencing and novel cancer immunotherapy. The combined approaches are behind a proof-of-concept clinical trial for patients with lethal metastatic prostate cancer.  

PCF Challenge Awards fund projects that bring together experts from a number of related fields to form a team focused on the creation of innovative, effective therapies for advanced prostate cancer. As part of Columbia’s grant, the new clinical trial will take place at the James J. Peters VA Medical Center (also known as the Bronx VA), a partner of Columbia University Irving Medical Center (CUIMC) and New York-Presbyterian .

PCF is recognized as the leading philanthropic organization for prostate cancer research. For the team at Columbia’s Herbert Irving Comprehensive Cancer Center (HICCC ), receiving a Challenge Award from the foundation was more than just an exciting achievement. It underscores CUIMC’s continued commitment to strengthen and expand its expertise in prostate cancer research and care through investments in faculty recruitment, enhanced emphases on bolstering basic science research and clinical trials centered on the disease and direct engagement with PCF. 

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January 16, 2019

The Gates Foundation Funds the Wang Lab’s Efforts in Global Health Study

Wang Lab
Ravi Sheth (left) and Harris Wang, PhD

Dr. Harris Wang , PhD, and systems biology graduate student, Ravi Sheth , have been awarded a new grant from the Bill and Melinda Gates Foundation to help advance a global health project aimed at reducing childhood mortality in sub-Saharan Africa. The project incorporates Dr. Wang’s innovative microbiome research techniques and applies them to study the antibiotic, Azithromycin, towards understanding its role as an intervention for improving childhood survival rates in rural low-income, low-resource settings.

The study supported by the Gates grant expands on breakthrough research conducted in the MORDOR study , a cluster-randomized trial in which communities in Malawi, Niger and Tanzania were assigned to four twice-yearly mass distributions of either oral Azithromycin or placebo. Children, as young as 12 months of age, participated, and results indicated that the all-cause mortality rate was significantly lower for communities receiving the antibiotic versus placebo. 

“This is an extremely exciting and, in many ways, very surprising result for such an underserved population,” says Sheth, who is a fourth-year PhD student in the systems biology track at Columbia University Irving Medical Center (CUIMC) . “Now it is crucial to understand how Azithromycin is acting to increase survival in such a profound way – to aid scale-up of the intervention and to help optimize the treatment regime and minimize any unintended consequences.” 

The researchers will focus on developing a mechanistic understanding of how Azithromycin reshapes the gut microbiome, and how this altered microbiome state affects the host. The effect of the antibiotic will be studied over space and time to understand the perturbation to the gut ecosystem and resulting community re-configuration and re-assembly, and this information will be utilized to predict and test optimal dosing strategies. 

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January 4, 2019

Advancing the Use of Single-Cell Technology for Novel Brain Cancer Treatment

Peter Sims, PhD
Peter Sims, PhD

The Mark Foundation for Cancer Research has awarded Peter Sims , PhD, an Emerging Leader Award and will support his work to advance a novel use of single-cell RNA sequencing to develop brain cancer treatments. Dr. Sims, assistant professor of systems biology at Columbia University Irving Medical Center, is one of just eight recipients of the inaugural grant, given to promising early career scientists for projects aimed at substantially unmet needs in cancer risk prediction, prevention, detection and treatment. 

Dr. Sims is an early contributor to the emerging field of large-scale single-cell RNA sequencing, which has made it possible to analyze tens of thousands of cells while simultaneously obtaining imaging and genomic data from each individual cell. He will be using this approach to improve patient-derived models of glioblastoma multiforme (GBM), an aggressive form of cancer that invades the brain, making complete resection difficult. In other words, making it extremely difficult in surgery to remove all cancerous cells from the brain. To date, drug therapies for this type of aggressive brain cancer have had limited success, partly because of the heterogeneity of these tumors. Furthermore,  current patient-derived models for researching glioblastoma do not fully recapitulate the cellular diversity of tumor cells that are present in the tumor, so it is extremely challenging to classify those cells in order to match them with the drug therapies that work. 

Indeed, there is a critical need to better characterize and understand GBM. Dr. Sims has collaborated with several brain tumor experts in the Herbert Irving Comprehensive Cancer Center , including Drs. Peter Canoll, Jeffrey Bruce, Antonio Iavarone and Anna Lasorella to advance single-cell genomic approaches to characterizing this disease. Approaching this problem at the single cell level could result in development of novel treatments that  prioritize and identify the specific drug therapies that may actually work on diminishing these tumor cells. The ultimate goal is to attain better predictions of therapeutic efficacy. 

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December 4, 2018

Innovative Engine: Medical Research

Researchers at the Vagelos College of Physician & Surgeons are rewriting the course of scientific investigation, intent on speeding up the process of discovery that will help patients with cancer, Alzheimer’s disease, diabetes, and other intractable diagnoses.

In cancer, Andrea Califano, Dr, the Clyde and Helen Wu Professor of Chemical and Systems Biology and chair of the Department of Systems Biology, decided to turn cancer treatment theory on its head. The first wave of research in pursuit of personalized oncology focused on clues embedded within individual tumors. Decode the nucleic acids gone awry within the DNA of a particular patient’s cancer, or so the thinking goes, to identify treatments tailored to target that specific mutation.

It’s a fine theory, says Dr. Califano in the article, but investigators still have a lot of work to do before the vast majority of cancers yield to that approach. “Only maybe 25 percent of patients have a mutation that could be defined as actionable,” he says.

For more than a decade, Dr. Califano has championed what might be considered an end run around cancer mutations, focusing instead on identifying and blocking the networks of normal proteins—known as master regulators—hijacked by deranged DNA to spur tumor formation and sustain tumor growth. Prevent the signals those proteins send on behalf of a cancerous mutation, and the cancer itself screeches to a halt.

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