Precision Nanomedicines for the Research, Detection, and Treatment of Cancer
Abstract: Our laboratory develops nanotechnologies to address problems in the diagnosis, treatment, and research of cancer and allied diseases: Therapy based on personalized medicine—the genomic context of a patient’s disease—has become a leading strategy to treat cancer. Small molecule drugs such as kinase inhibitors, which target key effectors of cancer signaling pathways, constitute a major component of this strategy. However, such drugs can affect the same signaling pathways in healthy tissues, which often leads to dose-limiting toxicities. Increasing the therapeutic index of targeted therapies would greatly improve their effectiveness. My laboratory is investigating new targets to localize precision drugs to the microenvironment of primary and metastatic tumors. We recently developed a nanoparticle drug carrier platform with nanomolar affinity to P-selectin to localize targeted therapies in tumor-associated vasculature and away from healthy tissues to obviate dose-limiting toxicities and concomitantly improve therapeutic index. We found that the nanoparticles targeted chemotherapeutics, as well as MEK and PI3K inhibitors, to tumor sites in both primary and metastatic models, resulting in superior anti-tumor efficacy and the striking reduction of toxicities. Moreover, measurements of tumor tissue show prolonged inhibition of downstream effectors in the signaling pathways, constituting a significant modulation of drug pharmacokinetics. In tumors devoid of P-selectin, we found that ionizing radiation guided the nanoparticles to the disease site by inducing P-selectin expression, suggesting a potential strategy to target disparate drug classes to almost any solid tumor. The early detection of cancer could lead to improved therapeutic responses and vastly improved patient outcomes. We aim to identify cancer biomarkers within the body at early disease stages, permitting detection before symptoms arise. We are developing implantable nanosensors, using the unique optical properties of carbon nanotubes, to facilitate non-invasive detection via optical detection through living tissues. The sensors could enable early detection of cancer in people at high risk for the disease, in successfully treated patients to monitor recurrence, or in patients who are undergoing treatment to inform clinical decisions. Bio: Dr. Daniel Heller is an Assistant Member in the Molecular Pharmacology Program and the Center for Molecular Imaging and Nanotechnology at Memorial Sloan-Kettering Cancer Center and an Assistant Professor in the Department of Pharmacology at Weill Cornell Medical College of Cornell University. His work focuses on the development of nanoscale technologies for the treatment, diagnosis, and research of cancer. Dr. Heller obtained his PhD in chemistry from the University of Illinois at Urbana-Champaign in 2010. He completed a Damon Runyon Cancer Research Foundation Postdoctoral Fellowship in the laboratory of Robert Langer at the David H. Koch Institute for Integrative Cancer Research at MIT in 2012. He is a 2012 recipient of the National Institutes of Health Director’s New Innovator Award, a 2015 Kavli Fellow, and a 2017 recipient of the Pershing Square Sohn Prize for Young Investigators in Cancer Research. Molecular Engineering and Sciences Seminar Series This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty. |