Funded Research

Uniting Against Lung Cancer funds scientific research that aims to enable patients to win their battles with lung cancer and live healthy lives years after diagnosis. Search our portfolio:


Evolution and impact of tumor molecular heterogeneity on response to EGFR-targeted lung cancer therapy

Collin Blakely, MD, PhD
University of California, San Francisco

Sponsored by Uniting Against Lung Cancer and Free to Breathe
Funded 2013

Summary
Activating mutations in EGFR are present in ~15-20% of patients with non-small cell lung cancer (NSCLC), with the majority of these occurring in never-smokers. While most EGFR-mutant NSCLC patients initially respond to treatment with an EGFR-targeted therapy, essentially all patients develop drug resistance. Dr. Blakely’s research is aimed at understanding how tumors develop resistance and developing new, effective treatments. His team analyzed the genetic diversity of a patient’s lung cancer and found evidence of two distinct types of cells within the same tumor, with different driver mutations. Dr. Blakely hypothesizes that this genetic diversity within a lung tumor promotes tumor progression dictates response and resistance to EGFR-targeted therapy. His project will use model systems to determine whether tumor genetic diversity affects growth and resistance, and correlate those results with lung cancer patients’ responses to EGFR-targeted therapy.


Targeting the BCL-2 Family in Small Cell Lung Cancer

Emily Cheng, MD, PhD
Memorial Sloan-Kettering Cancer Center

Sponsored by The Judy & Fred Wilpon Foundation and Tishman Speyer
Funded 2013

Summary
Small cell lung cancer (SCLC) represents 15% of all lung cancer cases, affecting approximately 30,000 people annually in the United States. The prognosis for patients with SCLC is poor, with only 5% of patients surviving five years, and there has been little change to treatment in 30 years. Dr. Cheng is developing a new treatment for SCLC, targeting the BCL-2 family of genes. She will be performing preclinical studies of a new drug combination in patient-derived cell lines and other preclinical models.


Treating metastasis by differentiation therapy: Identifying druggable pathways

William Cheung, PhD
Yale University

Sponsored by The Tom Zangas Memorial Lung Cancer Foundation and The Michael R. Pascucci Lung Cancer Association
Funded 2013

Summary
The majority of lung cancer patients are diagnosed with late-stage disease, when the tumor has spread to other parts of the body (metastasized). At this late stage, treatment options are very limited, and the survival rate is low. Dr. Cheung’s work is aimed at understanding how cells are able to metastasize and identifying new targets for therapies. His project will assess a specific protein required for cancer cell survival and invasion, SRC, and test whether blocking SRC activity is a viable treatment strategy for metastatic lung cancer.


Combination screening of targeted therapies as a strategy to understand and overcome resistance to EGFR inhibitors in lung cancer patients

Curtis Chong, MD, PhD
Dana-Farber Cancer Institute

Sponsored by The Marjorie M. Fisher Fund and The Tighe-Hidalgo Foundation and The Office of Dr. David Hidalgo
Funded 2013

Summary
Activating mutations in EGFR are present in ~15-20% of patients with non-small cell lung cancer (NSCLC), with the majority of these occurring in never-smokers. While most EGFR-mutant NSCLC patients initially respond to treatment with an EGFR-targeted therapy, essentially all patients develop drug resistance. Dr. Chong aims to identify targeted therapies and existing drugs that overcome resistance to EGFR-targeted therapy in lung cancer patients with an activating EGFR mutation. He will test a collection of 1200 existing targeted therapies in combination with an EGFR-targeted drug to identify additional therapies that reverse resistance. The most promising combinations will tested in tumor samples from lung cancer patients. These combination treatments may ultimately extend the duration of patient response to treatment.


Identifying potential driver mutations in gene promoters in a cohort of completely sequenced NSCLC genomes

Subhajyoti De, PhD
University of Colorado, Denver

Sponsored by Elliot's Legacy and Joan's Legacy
Funded 2013

Summary
Targeted therapies can be very effective in lung cancer patients whose tumors have specific driver mutations. However, 30% of lung tumors have no identifiable driver mutation within the classic cancer genes. Dr. De will perform a systematic survey to identify novel driver mutations that affect regulation of key cancer pathways in non-small cell lung cancer. This research aims to discover a new class of regulatory driver mutations in NSCLC, which contribute to tumor initiation and growth by changing expression of critical cancer genes.


Leveraging genetically engineered preclinical models of small cell lung cancer for advanced therapeutic studies

Anna Farago, MD, PhD
Massachusetts General Hospital / Massachusetts Institute of Technology

Sponsored by Elliot's Legacy and Joan's Legacy
Funded 2013

Summary
Small cell lung cancer (SCLC) is among the most aggressive and lethal solid tumor malignancies, yet research advances have been few and treatment outcomes have been virtually unchanged over the past 30 years. While chemotherapy initially induces a response in most patients, metastatic disease invariably recurs and is often resistant to additional conventional therapies. To date, there are no effective targeted therapeutic approaches in SCLC and research efforts to develop new therapeutic strategies for these cancers have lagged far behind those for non-small cell lung cancer. Dr. Farago will be using genetically engineered preclinical models of SCLC to test new therapeutic combinations and assess gene expression profiles of sensitivity and resistance. Ultimately, this work may lead to new targeted therapies for SCLC.


Epigenetic inhibitors in personalized therapy for Brg1 and EGFR mutant lung tumors

Christine Fillmore, PhD
Children's Hospital Boston

Sponsored by Joan's Legacy in honor of Meryl Bralower
Funded 2013

Summary
Chemotherapy is generally not considered curative for lung cancers, however, there is promise in combining chemotherapy with targeted therapies. Dr. Fillmore is investigating inhibiting epigenetic targets (proteins and genes that control expression of many other genes and cellular pathways). However, given the genetic complexity of lung cancer, it is important that these drugs be tested in models that mimic lung tumors found in patients. Dr. Fillmore hopes to also uncover mutations that can be used as biomarkers to predict efficacy of combining these inhibitors with chemotherapy, personalizing treatment for each patient.


Identification of Constitutional Risk Genes for Non-Small Cell Lung Cancer Adenocarcinoma

Zeynep Gumus, PhD
Mount Sinai Medical Center

Sponsored by The Ira Waldbaum Family Foundation and The Malinsky Family Charitable Trust
Funded 2013

Summary
Nearly 20% of lung cancer patients are never-smokers, and a significant risk factor for lung cancer is a family history of the disease. These factors suggest that some families may have a genetic hereditary predisposition to lung cancer. Dr. Gumus has identified a number of candidate risk genes (similar to the BRCA gene for breast cancer), and will be validating her findings in a larger, diverse group of NSCLC patients and controls. The long-term goal of this project is to identify a diagnostic panel for diagnosis of individuals at risk for lung cancer. The panel will allow the development of precisely tailored approaches and therapies for those NSCLC high-risk individuals and their families, improving patient outcomes and reducing overall healthcare costs.


DHHC Protein Palmitoyltransferases in Small Cell Lung Cancer

Sandra Hofmann, PhD
University of Texas Southwestern Medical Center

Sponsored by Elliot's Legacy and Joan's Legacy
Funded 2013

Summary
This project aims to identify a new class of targets for lung cancer therapy. Dr. Hofmann will be investigating a new family of enzymes (the DHHC family) that regulates protein function, focusing on DHHC5, an enzyme required for lung cancer growth. Her team will explore the role of DHHC5 in small cell lung cancer and understand the mechanism of DHHC5 protein overexpression in lung cancer. This work will help predict which patients would ultimately respond to drugs targeting this family of proteins.


Novel druggable pathway required for lung cancer progression and metastasis

Ann Marie Pendergast, PhD
Duke University Medical Center

Sponsored by The Hank Thompson Fund and Lily’s Light and The Caine Halter Fund for Lung Cancer Research
Funded 2013

Summary
Dr. Pendergast will investigate targeting the two Abl family kinases, Abl and Arg, in lung adenocarcinoma. Her team identified a role for Abl kinases in the progression and metastasis of some NSCLC tumors, characterized by poor prognosis and few therapeutic options. In addition, new data predicts Abl kinases to be involved in over 15% of lung tumors. Dr. Pendergast’s team will investigate the role of Abl kinases in lung adenocarcinoma tumor progression and metastasis, and test whether inhibiting Abl kinases can resensitize drug-resistance tumors to treatment.


Determining the mechanisms of intrinsic and acquired resistance to the 3rd generation EGFR inhibitor CO-1686

Matthew Niederst, PhD
Massachusetts General Hospital Cancer Center

Sponsored by Pershing Square Capital Management, LP and Joan's Legacy
Funded 2013

Summary
Personalized, targeted therapies have been effective in patients with non-small cell lung cancers, often inducing shrinkage of the tumor and a reduction in symptoms. Unfortunately, these patients eventually develop resistance to the inhibitors and the tumors begin to grow again, typically after one year. A secondary mutation that prevents the inhibitor from blocking the activity of the protein is responsible for the resistance in over half of patients. Next generation inhibitors have recently been developed that can block these resistant forms of the protein and hold great promise in resistant patients. Dr. Neiderst's project will focus on testing a next generation EGFR inhibitor in model cell lines derived from resistant patients in order to (1) determine which patients will benefit the most from the next generation inhibitors and (2) to develop novel therapies for patients who may not respond to these new drugs


Targeting LKB1-deficient non-small cell lung cancer through the NRF2 pathway

David Shackelford, MD, PhD
University of California, Los Angeles

Sponsored by Greenlight Capital and The Durst Organization
Funded 2013

Summary
Dr. Shackelford is investigating novel therapeutics for the treatment of early stage lung cancers harboring mutations in the LKB1 tumor suppressor gene. Through the use of state-of-the-art imaging and molecular analysis in human and preclinical models of lung cancer, his team will explore the use of β lapachone (β lap) as an anti-cancer agent to treat LKB1 mutant lung tumors. Dr. Shackelford will also investigate the contribution of oxidative stress to lung cancer, assess a related biomarker, and perform pre-clinical studies of a new therapeutic.


BET bromodomain inhibitor resistance in LKB1 deficient mutant KRAS NSCLC

Takeshi Shimamura, PhD
Loyola University Chicago

Sponsored by The Chicago Lung Run
Funded 2013

Summary
Between 15-30% of patients with NSCLC have tumors driven by the KRAS oncogene. Dr. Shimamura is focusing on two related proteins, LKB1 and Myc, regulating growth in tumors with KRAS mutations. His team will be investigating a new epigenetic drug that targets many Myc-related genes, and analyzing how LKB1 and KRAS signaling affects tumor responses to this drug. Using preclinical models, Dr. Shimamura will develop strategies to overcome resistance to this drug in mutant KRAS NSCLC with LKB1 mutations, guiding translation to early-stage clinical trials.


Impact of NF1 inactivation on the pathogenesis, signaling circuitry and therapeutic responsiveness of NSCLC in a novel co-clinical trial of targeted therapy.

Ferdinandos Skoulidis, MD, PhD
MD Anderson Cancer Center

Sponsored by Elliot's Legacy and Joan's Legacy
Funded 2013

Summary
Mutations in the NF1 gene, involved in growth, proliferation and survival, is a novel candidate oncogenic driver gene involved in up to 8% of all lung adenocarcinomas. Dr. Skoulidis will comprehensively evaluate the role of NF1 mutations in lung tumor development, and analyze the impact of NF1 mutations on response to molecularly targeted therapies currently in clinical trials. In addition, his team will identify biomarkers to predict which patients with NF1-driven tumors are more or less likely to respond to those targeted drugs.


Chromosomal Gains in Lung Squamous Carcinoma

Alison Taylor, PhD
Dana-Farber Cancer Institute

Sponsored by The Nancy Raisman Memorial Fund
Funded 2013

Summary
Chromosome numbers are altered in many tumors; instead of the normal two copies, the numbers vary. This is very common in lung squamous cell carcinomas (SCCs), where targeted treatments are currently not available. Over half of lung SCC patients have a particular chromosomal change - extra copies of one arm of chromosome 3, named chromosome 3q. Dr. Taylor will investigate the role of this chromosomal exchange in SCC through analyzing sequencing databases and utilizing various preclinical models. Validating this pathway in SCC will lay the groundwork for future development of new, targeted treatments.