Lung Cancer

Current Projects
Piro Lito, MD, PhD

Therapies that directly target cancer-promoting oncoproteins have revolutionized the treatment of cancer. Cancers, however, are primed to adapt and evolve in the presence of treatment, resulting in an ability to resume growth despite the presence of therapy. Utilizing cutting-edge new techniques that allow the determination of genetic alterations in single cancer cells, Piro aims to understand the principles that govern the evolution of resistance during therapy and identify novel therapeutic interventions that halt this process. His specific focus will be on resistance of lung cancer and melanoma to BRAF-targeted therapies. 

Project title: "Modeling the evolution of resistance to ERK signaling inhibitors at the single cell level"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Neal X. Rosen, MD, PhD, and Charles M. Rudin, MD, PhD
Cancer Type: Lung, Skin
Research Area: Experimental Therapeutics
Aaron L. Moye, PhD

Dr. Moye is studying early-stage lung cancer. Specifically, he is investigating the cell-to-cell cross talk between lung cancer cells and their surrounding microenvironment and how this cellular communication promotes early-stage lung cancer initiation and progression. Dr. Moye aims to discover secreted factors that can be used in diagnosis and to identify new targets for drug development that interfere with the lung cancer microenvironment.

Project title: "Role of Lgr6-expressing Mesenchymal cells in lung cancer initiation and progression"
Institution: Boston Children's Hospital
Award Program: Fellow
Sponsor(s) / Mentor(s): Carla Kim, PhD
Cancer Type: Lung
Research Area: Cancer Genetics
Matthew G. Oser, MD, PhD

Although small cell lung cancer (SCLC) is initially highly responsive to chemotherapy, the disease recurs in nearly all patients in less than a year. There are currently no approved targeted therapies for when the cancer returns. Previous studies have demonstrated that SCLCs require sustained neuroendocrine differentiation for survival, suggesting that targeting this process could be a good therapeutic strategy. Dr. Oser will use SCLC patient-derived xenograft models and a novel SCLC genetically engineered mouse model to identify new enzymes required for neuroendocrine differentiation and to develop targeted therapies that can block this process. He aims to identify molecular targets that could be developed into new lasting therapies for SCLC patients. Dr. Oser works under the mentorship of William G. Kaelin Jr., MD, at the Dana-Farber Cancer Institute, Boston.

Project title: "Targeting neuroendocrine differentiation as a novel therapeutic strategy for small cell lung cancer"
Institution: Dana-Farber Cancer Institute
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): William G. Kaelin, Jr., MD
Cancer Type: Lung
Research Area: Experimental Therapeutics
Geoffrey R. Oxnard, MD

Analysis of tumor DNA has transformed cancer care, allowing researchers to identify unique vulnerabilities within some cancers and treat them with highly effective, yet tolerable, targeted therapies. Moreover, emerging technologies now allow detection and analysis of tumor DNA which is circulating freely within the blood of cancer patients. Such “liquid biopsies” hold promise in their ability to accelerate the delivery of targeted therapies to appropriate cancer patients, while also allowing noninvasive monitoring of treatment outcome. Dr. Oxnard [Gordon Family Clinical Investigator] has recently developed a rapid noninvasive test for detection of tumor-derived DNA mutations in the blood of lung cancer patients, and has now launched this for clinical use at his institution. His research aims to validate that such liquid biopsies are ready for widespread adoption in guiding the care of lung cancer patients, while working to develop next generation assays that can comprehensively characterize cancer biology and identify the emergence of treatment resistance.

Project title: "Clinical translation of plasma cell-free DNA (cfDNA) genotyping technologies for NSCLC care"
Institution: Dana-Farber Cancer Institute
Named Award: Damon Runyon-Gordon Family Clinical Investigator
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Pasi A. Janne, MD, PhD
Cancer Type: Lung
Research Area: Diagnostics
Philip A. Romero, PhD

Dr. Romero is a biomedical engineer whose expertise is in the area of microfluidics. He proposes to develop new technology that can be used to detect circulating tumor cells (CTCs) in the bloodstream. CTCs are cells that have detached from a solid primary tumor and entered into the bloodstream; they can go on to colonize distant sites and form metastases. Detecting CTCs is an enormous challenge, as the cells are present at an ultra-low abundance (1 out of billions of blood cells). His approach is to develop a highly specific system, a “DNA-based logic circuit,” to detect and profile CTCs, which could ultimately be applied for cancer diagnosis, prognosis indication, and measurement of a patient’s response to treatment.

Project title: "Digital circulating tumor cell detection using scalable molecular logic"
Institution: University of Wisconsin, Madison
Award Program: Innovator
Cancer Type: Breast, Colorectal, Lung, Prostate, Sarcoma
Research Area: Biomedical Engineering
Rabi Upadhyay, MD

Immunotherapies using checkpoint inhibitors have shown amazing results in certain solid cancers. However, there are vast differences in treatment outcomes for patients who have remarkably similar cancers (based on histology and genetics) and many patients develop resistance. In addition, predicting who will benefit from the treatment has been unreliable. Recent research found that the diversity and specific quality of microbes that colonize the intestines (the gut microbiome) can impact the success of cancer immunotherapy, but there is no consensus about the underlying mechanisms. Dr. Upadhyay aims to build a mouse model of lung cancer that replicates the previous findings and then dissect the intricate biology between the gut microbiota and tumors in the lung. He plans to further define the cells and molecules involved, with the hope that more effective immunotherapy treatments can be designed for patients.

Project title: "Determining the distal effects of gut microbiota on the lung tumor microenvironment, cancer progression, and checkpoint blockade efficacy"
Institution: New York University School of Medicine
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Dan R. Littman, MD, PhD
Cancer Type: Lung
Research Area: Immunotherapy
Dian Yang, PhD

Dr. Yang  is examining tumor heterogeneity in search of new diagnostic markers and potential therapeutic targets. A tumor consists of not only cancer cells, but also immune cells, fibroblasts and other stromal components. The diverse cell types and cell states may promote disease progression and lead to therapeutic resistance, which is one of the greatest challenges in precision medicine. Dr. Yang aims to understand how heterogeneity is generated and regulated by using single cell functional genomic tools.

Project title: "Dissecting intratumoral heterogeneity and hierarchy at single cell resolution"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Jonathan S. Weissman, PhD, and Trever G. Bivona, MD, PhD
Cancer Type: Lung
Research Area: Cancer Genetics
Roberto Zoncu, PhD

Cancer cell metabolism differs from that of healthy cells because cancer cells have extreme requirements for energy. An organelle inside the cell called the lysosome has recently been defined as a “metabolic signaling center,” which senses cellular nutrient levels and communicates them to a growth regulator protein called mTORC1. Dr. Zoncu proposes to synthesize novel molecules that can specifically disable the lysosomal-mTORC1 signaling pathway as a new means of starving cancer cells and thus blocking tumor growth. He will investigate how this pathway controls the function of the lysosome and another organelle, the mitochondria, in mediating the resilience of cancer cells to challenges such as starvation, hypoxia and chemotherapeutic drugs. This research may impact all cancer types, but particularly pancreatic and lung cancers, which appear to be uniquely sensitive to levels of mTORC1.

Project title: "Identifying and disabling organelle circuits that fuel cancer cell metabolism"
Institution: University of California, Berkeley
Award Program: Innovator
Cancer Type: Lung, Pancreatic
Research Area: Cell Biology
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