CCOS is pleased to announce a new series of hub highlights featuring the innovative clinical and translational science coming out of the CTSA Program. We plan to feature groundbreaking work from each hub in the CTSA program over the coming months, selected at random. Our first hub under the metaphorical microscope is Weill Cornell Medicine (WMC) Clinical and Translational Science Center (CTSC) spearheaded by its founding director, Dr. Julianna Imperato-McGinley.
Knowing the signs of a metastatic cancer before it colonizes another part of the body could be a life saver for patients with pancreatic cancers. Spurred on by previous research showing that pancreatic cancers prime a location in the body, most often the liver, before colonizing that location, Weill Cornell Medicine researcher and CTSC Pilot Awardee Dr. David Lyden, in collaboration with Dr. Linda Bojmar, set out to find molecular indicators of liver colonization. The multi-institutional team identified an anomaly in liver biopsies from patients with quickly metastasizing pancreatic cancer — an increased presence of neutrophil extracellular traps (NETs). NETs are normally deployed by the immune system to thwart invading pathogens but are also implicated in tissue damage and metastasis. The presence of NETs can allow clinicians to identify aggressive pancreatic cancers that are preparing to spread, giving clinicians an opportunity to start treatment before metastasis. The NETs themselves could become a therapeutic target, with researchers already working on ways to destroy them once released.
Weill Cornell Medicine researcher Dr. Bishoy M. Faltas, an oncologist who specializes in urothelial cancers at WCM, is also exploring the early stages and development of bladder cancer, paving the way for more potential therapies. With support from a CTSC Pilot Award, Dr. Faltas has shown that a different antimicrobial defense, APOBEC3 enzymes, which protect the host by mutating the DNA of invading retroviruses, can also play a role in initiating bladder cancer by altering the host’s own DNA. Unfortunately, standard bladder cancer chemotherapy can also lead to more cancer-causing mutations, worsening the disease. Adding even more complexity to this cancer is the presence of abnormal DNA structures within tumor cells that contain overactive genes, which can impart resistance to therapy. These three discoveries highlight the need to adapt how clinicians treat bladder cancers, and also shed light on new therapeutic targets and strategies that Weill Cornell researchers are planning to explore.
The cancer therapeutic innovation doesn’t stop there. CTSC KL2 Scholar alumnus Geoffrey Markowitz, Ph.D., with his mentorship team, Dr. Vivek Mittal and Dr. Nasser Altorki at Weill Cornell Medicine and Dr. Andrea Schietinger at Memorial Sloan Kettering Cancer Center, has focused on reprogramming the body’s immune system. In the case of an overactive immune system, T cells can secrete compounds like PD-1 to bring the immune response back under control and prevent tissue damage. Though only successful in a minority of patients, some anticancer therapies known as checkpoint inhibitor therapies block this immune suppression to kill cancerous cells. The Mittal Lab has found a way to increase the effectivity of this therapy by increasing the number of T cell precursors, providing a potential army of cytotoxic T cells ready to be called upon when a tumor is detected. T cells could even be manipulated in the lab and administered to the patient as a more effective form of cell-transfer anticancer therapy.
These three research endeavors exemplify the mission and vision put forth in the new NCATS Strategic Plan. These insights provide ways to detect and target various types of cancers before they progress, increasing the likelihood of patient survival and decreasing the need for more invasive treatments later in the disease’s progression. Barriers have been broken and the efficiency of cancer treatment can be boosted via these discoveries.
Of note, all of these endeavors involved multi-institutional collaboration, bringing new research backgrounds and ideologies together from within and outside of Weill Cornell Medicine to tackle challenges in cancer treatment. Institutions like the Sandra and Edward Meyer Cancer Center, the New York Genome Center, and the Linköping University in Sweden all had a hand in these discoveries, which can enhance current cancer therapies and spark new innovations.
