Thoracic Surgery Cancer Biology Lab

The Thoracic Surgery Cancer Biology Laboratory, led by Laura A. Kresty, Ph.D., M.S., works to understand the complex mechanisms underlying lung and esophageal cancer development, progression and response to therapy. Our laboratory's work spans the research spectrum, from basic science and translational studies to clinical and health outcomes investigations with the ultimate goal of improving early diagnosis and developing improved strategies for the prevention and treatment of these cancers.

Each year in the United States, over 17,000 individuals are diagnosed with esophageal cancer and over 200,000[ with lung cancer. Both, unfortunately, carry high rates of morbidity and mortality. Hence, a tremendous need exists for new approaches to prevent cancer development, halt progression and metastasis and improve treatment efficacy. 

In the case of esophageal adenocarcinoma (EAC), chronic gastroesophageal reflux disease (GERD), can lead to Barrett's esophagus (BE), a precursor to this type of cancer. Mainstay treatments for GERD and BE include the use of proton pump inhibitors (PPIs), but nearly half of patients do not respond to PPI therapy and remain at elevated risk for cancer progression. While surgery or endoscopic therapy can be used to treat early stage cancer, individuals with more advanced disease often require chemotherapy and radiation treatment in addition to surgical care. Unfortunately, as many as two-thirds of patients who receive this type of combined modality treatment have minimal or no response. 

As a result, not only do we focus on new approaches to inhibit cancer development, progression and metastasis; we also work to improve our understanding of how genetic, host and environmental factors interact to mitigate patient-specific responses, including treatment resistance. Our researchers and clinician-scientists work together closely to investigate complementary aspects of lung and esophageal cancer biology via interrogation of the  transcriptome, cancer stem cells, the tumor microenvironment and microbiome. Our laboratory also has expertise and interest in assessing new drugs and natural products as cancer inhibitors. 

The researchers and clinician-scientists in our laboratory work closely to investigate a number of mechanisms and pathways to better understand how and why alterations in normal tissues support the development of precancerous conditions and elevate risk for progression to cancer. In turn, we focus on how we might impede these processes for improved patient outcomes. 

In the esophagus, our investigators look at how alterations in the process of DNA transcription impacts the development of cancer from BE. We also look at genetic changes related to lung cancer. In both types of cancers, we aim to find ways to lessen the impact of risk factors such reflux, which can lead to BE, obesity and smoking. 

Our lab also investigates select pharmcuetical drugs and well characterized natural products — including black raspberries and cranberry proanthocyanidins (C-PAC) — and their impact on signaling pathways involved in BE and progression to EAC. We aim to determine whether and how such agents can impede or slow cancer progression.

Our investigators have made important strides in the understanding of the mechanisms and drivers of cancer progression, from key transcriptional level changes to the many proteins and signaling molecules involved. The molecular characterization work highlights the large heterogeneity among patients, underscoring the need for a personalized and targeted approach to both treatment and prevention. We are investigating possible biomarkers for early detection of esophageal cancer in patients with BE and for lung cancer. One recent discovery has provided new potential insight into why esophageal adenocarcinoma mainly afflicts Caucasians, yet is rare in African Americans, pointing us toward potential new preventive approaches. 

We've shed light on the large impact of metabolomics, showing how preventive agents, including natural products like black raspberries and cranberry proanthocyanidins (C-PAC), can have a favorable impact on DNA damage and repair, bile acid profiles and the microbiome, in parallel with cancer inhibition in preclinical models. Importantly, we're learning how these varying factors interrelate and set a permissive stage for cancer development and progression.