Dr. Harvey Pass: Biomarker Pioneer

Key Facts

• Dr. Harvey Pass has led mesothelioma biomarker research at NYU for nearly two decades
• His laboratory has contributed to the development of multiple blood-based biomarkers including mesothelin and fibulin-3
• Mesothelin (SMRP) remains the only FDA-approved blood biomarker for mesothelioma
• Early detection through biomarkers could dramatically improve survival outcomes
• Pass co-founded the Mesothelioma Applied Research Foundation to advance patient-centered research

Mesothelioma is typically diagnosed late. By the time symptoms become severe enough to prompt a medical evaluation, the cancer has often spread beyond the point where surgery can remove it. This late detection is a major reason why the disease remains so deadly—patients are diagnosed when options are most limited.

Dr. Harvey Pass has spent much of his career trying to change this. As a thoracic surgeon turned researcher at NYU Langone Health, Pass has led the search for blood-based biomarkers that could detect mesothelioma earlier, before symptoms appear and while curative treatment might still be possible.

The quest is not yet complete, but the progress has been substantial. Biomarkers discovered and validated through Pass’s work are already changing how mesothelioma is diagnosed and monitored.

The Early Detection Problem

The challenge of early mesothelioma detection stems from the disease’s biology and typical patient population.

Late-appearing symptoms: Mesothelioma often causes no symptoms in its early stages. When symptoms do appear—shortness of breath, chest pain, unexplained weight loss—they can easily be attributed to more common conditions like bronchitis or pneumonia.

Non-specific imaging findings: Chest X-rays and CT scans can miss early mesothelioma or show abnormalities that don’t clearly indicate cancer. Pleural thickening, for example, can have many causes in people with asbestos exposure history.

Difficult biopsy: Definitive mesothelioma diagnosis requires tissue analysis, which typically means an invasive procedure. Physicians are reluctant to perform biopsies without strong evidence that cancer is present.

Known-risk population: Because mesothelioma is caused almost exclusively by asbestos exposure, we know who is at elevated risk—workers in certain industries, veterans, and their family members. This defined population creates an opportunity for screening that doesn’t exist for many cancers.

The goal of biomarker research is to develop a blood test that could be administered to people with asbestos exposure history, detecting mesothelioma at an early stage when treatment outcomes are significantly better.

The Biomarker Landscape

Pass’s laboratory at NYU has contributed to the discovery and validation of multiple mesothelioma biomarkers. The most important include:

Mesothelin (SMRP)

Soluble mesothelin-related proteins (SMRP) represent the most extensively studied mesothelioma biomarker. Mesothelin is a protein normally found on the surface of mesothelial cells. In mesothelioma, elevated levels are released into the blood.

Pass and colleagues at other institutions characterized SMRP and demonstrated its utility for:

• Diagnosis: Elevated SMRP levels can support mesothelioma diagnosis, particularly when combined with clinical and imaging findings.
• Monitoring: Serial SMRP measurements can track disease progression and response to treatment.
• Prognosis: Higher baseline SMRP levels correlate with worse outcomes.

SMRP is currently the only FDA-approved blood biomarker for mesothelioma. It is not perfect—sensitivity is limited, meaning some mesothelioma patients have normal levels—but it provides valuable information that complements other diagnostic tools.

Fibulin-3

Research from Pass’s group and collaborators has shown that fibulin-3 may have the highest sensitivity and specificity of any blood-based mesothelioma biomarker tested to date.

Fibulin-3 is a glycoprotein involved in cell structure and signaling. Elevated levels in blood and pleural fluid can:

• Differentiate mesothelioma from individuals with benign pleural conditions
• Distinguish mesothelioma from other malignancies causing pleural effusions
• Identify mesothelioma in asbestos-exposed individuals without clinical disease

While not yet FDA-approved, fibulin-3 is used in some clinical settings and continues to be validated in ongoing research.

Additional Biomarkers

The NYU group has also investigated:

• Osteopontin: A protein elevated in various cancers including mesothelioma
• HMGB1: A nuclear protein that, when released into the blood, indicates cellular stress or damage
• 13 SOMAmer panel: A multi-marker panel using aptamer technology that may improve diagnostic accuracy beyond any single biomarker

The trend in biomarker research is toward panels of multiple markers rather than reliance on any single test. Combining biomarkers can increase both sensitivity (finding more true cases) and specificity (reducing false positives).

From Surgeon to Scientist

Pass’s path to biomarker research began in the operating room. As a thoracic surgeon, he operated on mesothelioma patients and observed firsthand the limitations of treating disease that was diagnosed too late.

He was among the first surgeons to investigate photodynamic therapy for thoracic cancers—using light-activated compounds to kill cancer cells. This work led him deeper into mesothelioma research and eventually to the conviction that earlier detection was essential to improving outcomes.

At NYU, Pass established the Thoracic Oncology Laboratory, which investigates biomarker signatures for both lung cancer and mesothelioma. The laboratory’s work is supported by the National Cancer Institute’s Early Detection Research Network, which has funded the research since 2005.

The shift from surgeon to researcher was unusual for his generation, when physician-scientists often chose one path or the other. Pass maintained clinical practice while building a research program, arguing that direct patient contact kept the research focused on practical applications.

The Mesothelioma Applied Research Foundation

Beyond his laboratory work, Pass co-founded the Mesothelioma Applied Research Foundation (MARF), a nonprofit organization dedicated to ending mesothelioma through research, advocacy, and patient support.

As chairman of MARF’s Scientific Advisory Board, Pass has helped direct research funding toward promising projects and worked to ensure that patient perspectives inform research priorities. The foundation has funded millions of dollars in mesothelioma research, including early-stage projects that might not receive support from larger funding agencies.

The organization also provides patient support services and educational resources, recognizing that current patients cannot wait for future research breakthroughs.

Where Biomarker Research Stands

Despite decades of work, there is still no screening test for mesothelioma that can be recommended for widespread use in asbestos-exposed populations. The biomarkers developed so far are valuable for diagnosis and monitoring but have not yet achieved the sensitivity needed for early detection screening.

The challenge is the balance between sensitivity and specificity. A screening test must detect most true cases (high sensitivity) without generating too many false positives that lead to unnecessary procedures (high specificity). Achieving both simultaneously has proven difficult.

Current biomarkers perform best when used in combination with:

• Clinical risk factors (asbestos exposure history)
• Imaging findings (CT scans, chest X-rays)
• Symptoms and physical examination

They augment rather than replace traditional diagnostic approaches.

Future Directions

Research continues to pursue the goal of true early detection. Approaches under investigation include:

Multi-marker panels: Combining multiple biomarkers to improve accuracy beyond any single test. Machine learning approaches can identify optimal marker combinations.

Liquid biopsy: Analyzing circulating tumor DNA or cancer cells in blood samples. This technology has advanced rapidly for other cancers and is being applied to mesothelioma.

Exhaled breath analysis: Investigating whether volatile organic compounds in breath can indicate mesothelioma presence.

Improved mesothelin assays: Developing more sensitive tests for existing biomarkers.

The COVID-19 pandemic, ironically, accelerated some aspects of blood-based biomarker development by demonstrating that large-scale blood testing could be implemented quickly when needed. Some researchers hope this experience will benefit cancer screening efforts.

The Personal Dimension

For Pass, the work has always been personal. He has seen patients die from disease that might have been curable if caught earlier. He has operated on patients whose tumors had already spread beyond what surgery could address.

“We know this population is at risk,” he has noted. “We should be able to do better.”

The goal is not just early detection for its own sake, but early detection that leads to early treatment that leads to longer survival. For that to happen, mesothelioma treatment must continue to improve alongside detection capabilities.

Recent advances in immunotherapy have demonstrated that mesothelioma can respond to modern treatments in ways that were not possible even a decade ago. If patients could be diagnosed earlier—when tumor burden is lower and they are healthier overall—these treatments might prove even more effective.

The Road Ahead

Harvey Pass’s career represents a bridge between generations of mesothelioma medicine. He began when surgical removal of visible tumor was the primary treatment option and outcomes were uniformly poor. He helped establish the biomarker research program that may eventually enable early detection. And he has lived to see immunotherapy transform treatment for at least some patients.

The work is not finished. A blood test that can reliably detect early mesothelioma remains elusive. But the foundation for such a test has been built through decades of painstaking research—identifying candidate biomarkers, validating them in patient populations, understanding their strengths and limitations.

For the approximately 3,000 Americans diagnosed with mesothelioma each year, and for the larger population living with asbestos exposure history and the knowledge that they are at risk, this research represents hope. The goal of catching mesothelioma early—before it spreads, before symptoms appear, while cure is still possible—moves closer with each published study and each clinical trial.

That progress is Harvey Pass’s legacy: a field transformed from resigned acceptance of late diagnosis to active pursuit of early detection.