The first winning proposal by Drs. Harmeet Bedi, Bryan Hartley and Ben Berkowitz from Stanford University and the Stanford Byers Center for Biodesign, Diagnostic Bronchography: A Novel Approach to Peripheral Lung Nodule Diagnosis reimagines an older diagnostic approach with new technology that helps doctors see lung airways more clearly during biopsy procedures. The research team brings together expertise in pulmonology, diagnostic imaging and biomedical engineering to provide better biopsy precision that improves early lung cancer detection.
Enabling Earlier Lung Cancer Diagnosis Through Advanced Imaging
Lung cancer is the deadliest of all cancers, as it accounts for more deaths than breast, prostate, and colon cancers combined. The main reason for this is because lung cancer tends to be diagnosed after the cancer has spread to other locations within the body. The key to making lung cancer less deadly is to diagnose the lung cancer at an earlier stage, preferably when it is just a “spot in the lungs” on a chest x-ray or a CT scan. At this early stage, the cancer can be removed surgically with a relatively high cure rate. These “spots” are known as lung nodules, and they can represent either infections, non-cancerous tumors, or cancerous tumors. When a lung nodule is found, it is the doctor’s job to determine if the nodule is cancer. To help with this decision making, a doctor may send the patient for further tests and scans. If the lung nodule is thought to be suspicious for cancer, the doctor will send the patient for a “lung biopsy.” A lung biopsy is a procedure where a small piece of the nodule is collected and analyzed under a microscope to find out if cancer is the cause. Patients sometimes wonder why the doctor does not just remove the nodule with surgery if it is suspicious for cancer. The reason that all nodules are not removed is because many of these nodules, up to 30%, may actually not be cancer. Also, the surgery to remove the nodule is considered a major surgery, with many risks and potential complications. The worst outcome from this surgery would be if a patient develops a complication or even dies from the surgery, and it is determined that the nodule that was removed was not even cancerous. To avoid this outcome, the safest and least painful method to perform a biopsy for testing lung nodules is known as bronchoscopy. In bronchoscopy, a thin tube with a camera on the end is inserted through the mouth and into the lungs. The nodule is then biopsied by inserting biopsy tools through the thin tube towards the lung nodule. Bronchoscopy is known as the safest method for lung biopsy with the least complications compared with alternative techniques such as CT-guided biopsy and surgery. However, bronchoscopy is poor at determining whether or not the nodule is cancerous. The main reason that bronchoscopy is relatively poor at diagnosing lung nodules is because the doctor performing the procedure currently has limited tools and technologies available to successfully reach the nodule. The lungs are known to have thousands of airways, also known as bronchi, that branch and divide over and over again. This is very similar to navigating through a complex maze, so getting to the nodule successfully can be very difficult. To help doctors tackle this challenge and get an earlier diagnosis for patients, we are currently developing a completely new technique for doctors performing these procedures. This new technique is called “diagnostic bronchography” and will allow doctors performing bronchoscopy to see an exact airway map of the lungs and to plot a pathway using the map to reach the concerning lung nodule. This new method will use a technology known as “fluoroscopy,” also known as “live x-ray.” Fluoroscopic x-ray is currently used during lung biopsy, however, during traditional fluoroscopy, the airways of the lungs are invisible. Diagnostic bronchography is capable of displaying these previously invisible airways clearly, and in high resolution, on the video monitor. This will help doctors reach the nodules much more accurately than the best current technologies. We have already tested this new technique in the lungs of dead pigs and have achieved great success with demonstrating feasibility of the technique. Now, with our research proposal, we hope to test this technique for further feasibility in the lungs of living pigs. Additionally, we will test how successfully we can insert our biopsy instruments near implanted lung nodules or “fake nodules” that we have inserted into the lungs. This new technique truly has the potential to improve the chances of successfully diagnosing early lung cancers, before they have a chance to spread throughout the body. Through earlier diagnosis, patients can have more effective treatments that will allow them to live longer, cancer-free lives.
The second winning proposal by Drs. Nicholas Arpaia and Tal Danino from Columbia University’s Departments of Microbiology & Immunology and Biomedical Engineering, Engineered probiotics for precision lung cancer immunotherapy, develops a novel bacteria-based cancer therapy. Combining their expertise in lung cancer immunology and synthetic biology, the investigators will design probiotic bacterial strains that find and attack lung cancer.
Patient-specific lung cancer immunotherapy using probiotic bacteria
In recent years, the field of cancer immunotherapy has seen a renaissance. Newly developed antibody therapies have demonstrated unparalleled clinical success and activate a patient’s own immune system to fight cancer. Several of these therapies have gained FDA approval and are now part of routine treatment regimens for metastatic melanoma, bladder cancer, and non-small cell lung carcinoma. Herein, we describe an approach that uses synthetically engineered probiotic bacteria that specifically home to lung tumors, deliver rationally-designed immunotherapeutics, and induce durable, systemic, and curative antitumor immunity. Through the synergistic coupling of the applicants respective areas of expertise, they are working to develop bacterial lung cancer therapies that can be translated into into the clinic for patient benefit within the next 3 years. The successful completion of their outlined proposal objectives will help ALCF in achieving its goal of making lung cancer a chronically managed disease.