Joshua Reuss, MD, and Patrick Forde, MD, PhD, talked with moderator Isabel Preeshagul, DO, MBS, about developments from the 2026 IASLC Targeted Therapies of Lung Cancer meeting.
Watch the replay below.
AbbVie
Boehringer Ingelheim
Eisai
By Dhru Deb, PhD
Senior Director, Research and Administration, LCRF
For more than two decades I have been watching the field of lung cancer harboring EGFR mutation evolve from a mystery to a map, from a crisis to something many patients now live with for years.
Before we begin, an important note: the EGFR-mutation in lung cancer is one of the most extensively studied areas in oncology. What follows highlights selected milestones and investigators—particularly those supported by the Lung Cancer Research Foundation (LCRF)—but it is not a comprehensive history. Many other scientists, clinicians, collaborators, and, most importantly, patients, have driven this progress forward. Their contributions are deeply valued, even if not individually named here.
In the early 2000s, a lung cancer diagnosis often arrived with a quiet finality. The doctor might speak gently, choosing words like “aggressive,” while the details blurred together in the shock of the moment.
Sometimes the patient had never smoked. Sometimes they were in their early fifties, with a persistent cough that seemed ordinary at first—just something that wouldn’t go away. That was often how it began.
Back then, lung cancer was treated largely as one disease. Chemotherapy was the standard approach. Some patients responded. Many did not. There was no routine testing to look inside the tumor’s DNA. There was no roadmap.
Outcomes were often swift and unforgiving.
Family members would later learn that their loved ones likely had what we now call lung cancer harboring EGFR mutation—a subtype driven by specific changes in a gene called the epidermal growth factor receptor (EGFR). But in 2003, that knowledge had not yet reached the clinic.
In 2004, several research teams—including Thomas Lynch Jr., William Pao, Bruce Johnson, Tetsuya Mitsudomi, Katerina Politi, Mark Kris, Susumu Kobayashi, Pasi Jänne, Matthew Meyerson, Balázs Halmos —published landmark papers in The New England Journal of Medicine, PNAS USA, and Science. They identified specific EGFR mutations—most commonly exon 19 deletions and the L858R mutation—that made tumors exquisitely sensitive to drugs called EGFR tyrosine kinase inhibitors (TKIs).
For the first time, lung cancer was no longer one disease.
It was as if researchers had discovered that some tumors were powered by a single stuck accelerator pedal—and that there might be a way to ease off it.
Science moves forward because someone asks, “But how does it really work?”
Raffaella Sordella, supported early by LCRF, helped answer that question. Her work explored what scientists call “oncogene addiction”—the idea that certain cancers become biologically dependent on a single mutated pathway for survival.
Her research showed that EGFR mutations weren’t just markers that happened to predict response. They were the engine itself.
That biological clarity mattered. It gave physicians confidence that targeting EGFR wasn’t guesswork—it was rational medicine.
By 2009, the phase III IPASS trial (Mok et al., NEJM 2009) demonstrated that patients with EGFR mutations responded far better to EGFR inhibitors than to chemotherapy. Japanese trials such as NEJ002 and WJTOG3405 confirmed it (Mitsudomi et al., Lancet Oncology, 2010).
Testing tumors for EGFR mutations became essential.
Marc Ladanyi, also supported by LCRF, helped build the genomic infrastructure to make that testing reliable and routine. Without accurate molecular diagnostics, these scientific breakthroughs would never have translated into real lives extended.
For patients diagnosed in 2011—the difference was immediate. Instead of starting chemotherapy, they began erlotinib after their tumor tested positive for an EGFR mutation.
In some cases, within weeks, their cough eased. Their scans improved dramatically.
For the first time, some patients were experiencing what felt like a miracle: pills instead of IV chemotherapy. Tumors shrinking in months, not after endless cycles.
But cancer adapts.
By 2015, many patients who initially responded began to relapse. Researchers identified a common culprit: a secondary mutation called T790M.
It was heartbreaking. For patients who had tasted hope, progression felt devastating.
Katerina Politi, supported by LCRF, used genetically engineered mouse models to show that resistance was not random chaos. It was evolution under pressure. Tumors changed in predictable ways.
Trever Bivona’s work expanded that understanding further, revealing that resistance could arise through “bypass” pathways—like traffic detours around a blocked road.
The message was profound: resistance wasn’t failure. It was biology. And biology could be studied.
Scientists designed a third-generation drug—osimertinib—to specifically target the T790M resistance mutation while sparing normal cells.
The AURA trials and later the FLAURA trial (Soria et al., NEJM 2018; Ramalingam et al., NEJM 2020) showed improved progression-free and overall survival. Osimertinib became the first-line standard of care.
Jonathan Ostrem’s research into mutant-selective drug design helped refine how these targeted therapies bind precisely to altered proteins—like crafting a key that fits only the damaged lock.
For some patients, when their cancer progressed in 2016, a blood test—called a liquid biopsy—detected T790M in circulating tumor DNA. They switched to Osimertinib and their disease came under control.
Yet even osimertinib is not the end of the story.
Some tumors develop additional changes—MET amplification, C797S mutation, or even transform into a different type of cancer, such as small cell lung cancer.
Matthew Niederst, supported by LCRF, helped define this phenomenon of lineage plasticity—the idea that cancer cells can change identity under treatment pressure.
It was a sobering realization: cancer is not static. It evolves.
But now doctors monitor it in real time. Liquid biopsies, advanced genomic profiling, and structured sequencing strategies—refined by clinicians like Zofia Piotrowska—help guide what comes next.
Today, options after resistance include:
What once was a cliff is now, increasingly, a series of steps.
Two decades ago, a lung cancer harboring EGFR mutation diagnosis often meant months.
Today, many patients live years. Brain metastases—once especially devastating—can often be controlled with targeted treatments designed to cross into the central nervous system. As cancers evolve, patients may move through sequential targeted therapies, each tailored to new molecular changes. Quality of life, once an afterthought in the urgency of treatment, has become a central goal alongside longevity.
The journey is rarely simple. Patients may cycle through multiple lines of therapy. There are setbacks, scans that bring anxiety, and difficult decisions along the way. But there are also birthdays once feared lost, holidays once thought unreachable, futures that expand beyond the original prognosis.
For families who lost loved ones before these advances, the grief does not vanish. It lingers, reshaped but enduring. Yet many find meaning in witnessing how profoundly the story has changed—how scientific discovery has transformed a once-uniform diagnosis into a series of treatable, evolving chapters. And in that transformation, there is both remembrance and hope.
The transformation of Lung cancer harboring EGFR mutation reflects a complete arc of translational science:
LCRF’s sustained investment helped accelerate each step—supporting scientists willing to ask difficult questions before the answers were obvious.
For families who lost loved ones before these therapies existed, this progress carries both sorrow and meaning. For patients diagnosed today, it offers something once unimaginable:
The story of lung cancer harboring EGFR mutation is not finished. Resistance still occurs. Cure remains elusive. But what was once a rapidly fatal disease is now, for many, a chronically managed condition guided by molecular insight.
And every breakthrough rests on decades of research—and on the patients, donors, advocates and research partners who made that research possible.
Because science does not move forward alone.
This article originally appeared on LinkedIn.
NEW YORK, NY (February 24, 2026) – The Lung Cancer Research Foundation (LCRF) announces a new research collaboration with AstraZeneca aimed at driving progress in small cell lung cancer (SCLC) with two grant awards, 2026 LCRF | AstraZeneca Research Award on Strategies Towards Improving the Treatment of Small Cell Lung Cancer and 2026 LCRF | AstraZeneca Research Award on Strategies Using Patient Advocacy to Improve Outcomes in Small Cell Lung Cancer.
Lung cancer is responsible for more deaths worldwide than any other cancer, accounting for an estimated 124,990 deaths annually in the United States alone.1 Small cell lung cancer (SCLC) represents 13-15% of lung cancer cases with a 5-year survival rate of less than 7%.1,2 It is characterized by rapid proliferation and early metastatic spread. Only a small fraction of patients present with earlier stage disease that is amenable to potentially curative treatment with combined modality therapy. Lung cancer screening initiatives have resulted in a 20% reduction in mortality for non-small cell lung cancer (NSCLC), but have not had the same benefit for SCLC patients, probably because of the aggressive nature of the disease.
While there have been significant advancements in the treatment of NSCLC, there has been very little movement for SCLC, both in the understanding of the biology of SCLC and treatment. Recently, there has been a characterization of SCLC subtypes that may have distinct therapeutic vulnerabilities. Untreated SCLC is initially sensitive to DNA-damaging agents with impressive clinical response. Unfortunately, treatment resistance is inevitable and second-line therapy is less effective. The introduction of immunotherapy in first-line treatment has resulted in modest improvements in the treatment of extensive SCLC and a significant improvement in overall survival for patients with limited stage disease.3,4,5
There have been attempts at identifying targets for more directed treatment. DLL3, an inhibitory Notch pathway ligand, represents a potential therapeutic target in SCLC because it is frequently expressed on the surface of SCLC tumor cells. Discovering both biomarkers that predict treatment benefit and novel therapeutic targets represents a great area of need to make substantial progress in SCLC.
Considering that scientists are just scratching the surface when it comes to understanding the biology of SCLC and given that most therapeutic options available to date are usually not curative, there is a need for novel approaches to treat SCLC and improve outcomes for patients with the ultimate intention of cure.
Understanding the biology of a disease and developing treatments is often supported and amplified by patient advocacy. Diligent patient advocacy has been responsible for advancements in a number of diseases, including HIV/AIDS, breast cancer, and Alzheimer’s disease. Despite it being the leading cause of cancer deaths in the US, lung cancer has the smallest advocacy score of any major disease.6 One of the greatest barriers to developing effective advocacy initiatives has been the stigma associated with lung cancer. Given the limited research and clinical progress in SCLC, it is unsurprising that advocacy for this patient population represents a critical and urgent unmet need.
The 2026 LCRF | AstraZeneca Research Award on Strategies Towards Improving the Treatment of Small Cell Lung Cancer is a $500,000, three-year award that will focus on furthering the development of novel strategies towards improving the treatment of SCLC. Work supported through this mechanism will address important areas of need across the entire care continuum and have the immediate potential to increase survivorship. It is expected that correlative translational research will be proposed that will enhance the understanding of SCLC.
The 2026 LCRF | AstraZeneca Research Award on Strategies Using Patient Advocacy to Improve Outcomes in Small Cell Lung Cancer is a $250,000, two-year award that will focus on furthering the development of strategies towards improving the outcomes of SCLC patients through patient advocacy. Work supported through this mechanism will address important areas of need across the entire care continuum and have the immediate potential to increase research efforts, quality of life and survivorship.
“A deeper understanding of small cell lung cancer biology is essential to advancing more precise and effective therapies—and ultimately improving care and outcomes for people living with this challenging disease,” said Nabil Chehab, US Medical Head, Lung Cancer, AstraZeneca. “We’re proud to partner with the Lung Cancer Research Foundation to accelerate research and to engage patients and their support networks, moving small cell lung cancer science forward.”
“LCRF’s research program is centered on delivering solutions for lung cancer patients. Including patients in research ensures that their most pressing needs are met, both near-term and long-term,” says Dr. Antoinette Wozniak, Chief Scientific Officer for LCRF. “Patients are our partners in discovery and their voices help define research priorities and drive meaningful outcomes. Collaboration is the key to addressing unmet needs for the community. I know that AstraZeneca shares our commitment to provide hope through impactful research.”
Requests for Proposals will be announced in the coming months. To be notified when submission will be accepted, please visit LCRF.org/RFPlist.
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About the Lung Cancer Research Foundation (LCRF)
The Lung Cancer Research Foundation® (LCRF) is the leading nonprofit organization focused on funding innovative, high-reward research with the potential to extend survival and improve quality of life for people with lung cancer. LCRF’s mission is to improve lung cancer outcomes by funding research for the prevention, diagnosis, treatment, and cure of lung cancer. To date, LCRF has funded 450 research grants, totaling nearly $53 million, the highest amount provided by a nonprofit organization dedicated to funding lung cancer research. For more information about the LCRF grant program and funding opportunities, visit LCRF.org/research.
Contact:
Lung Cancer Research Foundation (LCRF)
Sheila Sullivan, Senior Director, Marketing & Communications
ssullivan@LCRF.org
LCRF’s science team discusses the 2026 research grant program, why LCRF and OUCH-I are backing research on environmental factors and lung cancer, and how previous research is connected with treatments that are now benefiting patients. Watch the clip below.
Featured:
Aubrey Rhodes, LCRF Executive Director
Dhru Deb, PhD, Senior Director, Research & Administration
Antoinette (Toni) Wozniak, MD, Chief Scientific Officer
> Read this year’s Request for Proposals
> Learn more about the LCRF | OUCH-I research grant
> Read Dr. Deb’s Connecting the Dots series
> Donate to fund lung cancer research
In a year when a lack of federal funding threatened to stall progress in lung cancer research, the lung cancer community certainly stepped up. Support from generous donors and fundraisers made it possible for LCRF to fund $5 million in research grants during 2025 – more than any other funding year in its history.
The record 21 projects funded were selected from hundreds of applications, representing some of the brightest minds committed to improving outcomes for lung cancer patients.
A wide range of topics are being studied, from novel disease targets, predicting which patients will benefit most from immunotherapy, targets for small cell lung cancer, strategies for inhibitor-resistant lung cancer, screening in emergency patients, and more. These projects demonstrate profound promise to make a sustained and lasting impact on lung cancer research and outcomes.
“Our Scientific Advisory Board and Research Advocates reviewed hundreds of submissions, and we’re excited to support the work of these grantees,” said Colleen Conner Ziegler, Chair of LCRF’s Board of Directors and a patient with stage 4 lung cancer. “Keeping patients’ voices at the forefront of the research process is of utmost importance to LCRF and is evident in the projects that were selected for funding.”
“Each year, we are presented with many ideas that have the potential to change how we approach lung cancer prevention, detection and treatment,” said Kathryn O’Donnell, PhD, chair of LCRF’s Scientific Advisory Board and Associate Professor, Molecular Biology, UT Southwestern Medical Center. “At LCRF, we’re committed to funding the most innovative research projects that will have a positive impact on the lives of people living with lung cancer.”
“Funding investigators early in their careers is often the catalyst to keeping scientists focused on advancing their best science,” Dr. O’Donnell added. “With the current uncertainties of federal funding, including the elimination of the Congressionally Directed Medical Research Program’s lung cancer program, funding from organizations like LCRF becomes even more important in maintaining momentum in lung cancer research.”
LCRF funds projects that demonstrate profound promise to make a sustained and lasting impact on lung cancer research and outcomes. The strength of LCRF’s research program is underscored by the trust, generosity, commitment, and vision of its partners, fundraisers, and donors.
“LCRF is grateful to everyone who has made this grant cycle the largest in its history – 21 grant awards for more than $5 million,” said Aubrey Rhodes, LCRF’s Executive Director. “Ensuring that lung cancer research maintains momentum in an uncertain funding environment is of utmost importance. LCRF is committed to filling the funding gap. Working toward improving survival for people with lung cancer is our priority.”
With this year’s grants, LCRF’s total active research portfolio supports more than $21 million in lung cancer research projects. More funding for research means greater opportunities to uncover advances that will have a positive impact for patients.
Research announcements:
I have been a Medical Oncologist for over 40 years, and I have had the privilege of witnessing an explosion of advancements in the treatment of lung cancer. It has now been over 20 years since EGFR’s pivotal role in lung cancer was fully realized. Since then, there have been a tremendous number of Federal Drug Administration (FDA) approvals for novel agents in the management of lung cancer.
In 2025, a number of novel agents were FDA approved for various forms of lung cancer.
This ‘Science Made Simple’ does not include all the progress that has been made this past year, but these FDA approvals represent important advances in areas of unmet need, emphasizing the importance of molecular testing and the participation of patients in clinical trials. These advances would not be possible without the contribution of patients by their willingness to participate in clinical research.
The 5-year survival rate for lung cancer has improved significantly, rising to 27% in 2025, compared to 17% in 2014. This result is attributed to advancements in treatment and early detection. 27% is clearly an improvement, but it is not good enough and more work needs to be done.
In the coming years, look for more drug approvals and efforts to detect lung cancer at an earlier stage, particularly in patients who do not meet the current screening criteria (i.e. never smokers).
Look for more advancements in the treatment of small cell lung cancer, which has been a particularly stubborn disease to treat but where there has been some recent progress.
LCRF continues to support researchers who are trying to understand the biology of lung cancer in order to develop novel therapies and overcome resistance to treatment.
The Food and Drug Administration (FDA) has approved amivantamab to be given under the skin, which is called a subcutaneous (SQ) injection, for adult patients with the same conditions where amivantamab is already approved to be given through a vein, or intravenously (IV).
Amivantamab is a type of treatment called a bispecific antibody, which means that it has two different targets, EGFR and MET. It has been approved for the treatment of non-small cell lung cancer (NSCLC) in several situations:
The SQ injection of amivantamab was evaluated in the PALOMA-3 trial. Over 400 patients with advanced NSCLC and common EGFR mutations received either SQ or IV amivantamab in combination with lazertinib.
The trial showed that patients who received SQ amivantamab had similar treatment responses and survival outcomes as patients who received IV amivantamab.
An important consideration for patients is safety and convenience. The safety profile of the SQ amivantamab was generally similar to the safety profile of the IV amivantamab, with one exception. Infusion reactions occurred less often for SQ amivantamab (13% of patients) compared to those who received IV amivantamab (66% of patients).
Other side effects with either form of amivantamab could still include interstitial lung disease/pneumonitis, venous thromboembolic events when used with lazertinib, skin rash, ocular toxicity, and embryo-fetal toxicity.
Another important factor is that the SQ administration allows patients to spend less time at their doctor’s office receiving amivantamab, which contributes to their overall quality of life.
The SQ administration of amivantamab is likely to replace the IV administration of the drug in most circumstances and could be employed in clinical trials as well. Research that is geared toward reducing side effects and changing drug administration in order to improve a patient’s quality of life is very important. It is likely that there will be more clinical trials evaluating other treatments with the sole purpose of reducing side effects and decreasing the time that patients spend getting their treatments.
La Dra. Coral Olazagasti y la Dra. Estelamari Rodríguez nos acompañaron a una discusión comunitaria sobre el cáncer de pulmón. Moderado por la Dra. Ana Velázquez Mañana, brindaron una descripción general del cáncer de pulmón y discutieron el diagnóstico y el tratamiento del cáncer de pulmón, las pruebas de biomarcadores y los ensayos clínicos, entre otros temas.
La Dra. Olazagasti es oncóloga de cabeza y cuello y oncóloga torácica en el Sylvester Comprehensive Cancer Center de la Escuela Miller de Medicina de la Universidad de Miami. La Dra. Rodríguez es codirectora del Grupo de Tumores Torácicos de la institución. La Dra. Velázquez Mañana es oncóloga torácica y catedrática adjunta de Medicina en la Universidad de California, San Francisco.
Ver la grabación aquí:
Coral Olazagasti , MD, and Estelamari Rodríguez, MD, MPH, led a Lung Cancer Community Talk in Spanish recently. With moderator Ana Velázquez Mañana, MD, MSc, they provided an overview of lung cancer, with a discussion about lung cancer diagnosis and treatment, biomarker testing, clinical trials, and more.
Dr. Olazagasti is a head & neck and thoracic oncologist for Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. Dr. Rodriguez is Co-Lead, Thoracic Site Disease Group for the institution. Dr. Velázquez Mañana is a thoracic oncologist and an Assistant Professor of Medicine at the University of California, San Francisco.
Radon is a naturally occurring radioactive gas, produced when uranium breaks down. This gas is released through rocks, soil, and water, and can build up in enclosed spaces through cracks in a building’s foundation or other openings. Because it’s invisible and odorless, radon exposure doesn’t cause immediate symptoms.
However, radon is the second-leading cause of lung cancer, resulting in more than 21,000 deaths every year in the U.S. It is the leading cause of lung cancer for non-smokers.
The highest concentrations of radon develop in spaces below ground level without much ventilation: basements, crawlspaces, foundations, sump pumps, and construction joints. While pockets of radon can be found across the country, some states have higher levels than others. Check your state’s radon levels here.
If you live in an older home, or in a state with higher radon levels, be sure to test your home for the presence of radon. Safewise.com recommends these six detectors.
How much radon is too much? Radon detectors measure levels in picocuries per liter (pCi/L) to indicate average, year-round radon levels. If your home measures between 2-4 pCi/L, consider taking steps to reduce radon levels. Higher than 4? Confirm the results, then take immediate action. The EPA offers more information here.
NEW YORK, NY (January 12, 2026) – The Lung Cancer Research Foundation (LCRF) and Oncology Advocates United for Climate and Health – International (OUCH-I) announce today that their collaborative research program, titled OUCH-International and LCRF Research Grant Program on the Effects of Air Pollution and Climate Change on Carcinogenesis and Lung Cancer Prevalence, is now accepting proposals. The two organizations are partnering to fund projects that examine the impact of environmental pollution and climate change on lung cancer risk, diagnosis, treatment and outcomes; along with innovative strategies to mitigate these effects. With support from AstraZeneca, the selected project will receive a $200,000 award over a two-year period.
Air pollution causes many health hazards, can contribute to the development of lung cancer, and can worsen its prognosis. Increasing evidence indicates that air pollution is a major cause of lung cancer, and the number of estimated lung cancer deaths attributable to air pollution has increased by nearly 30% since 2007, as smoking has decreased and air pollution has increased (Turner MC et al, CA Cancer J Clin, 2020). The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and particulate matter (PM) with a diameter of less than 2.5 microns (1 inch = 25,400 microns) as a cause of lung cancer (Straif K et al, IARC Press, 2013; Loomis D et al, Lancet Oncol, 2013; GBD 2019 Risk Factors Collaborators, Lancet, 2020). Data now show that exposure to pollution—whether from industrial sources or wildfires—increases the risk of lung cancer in both smokers and non-smokers (Hill et al, Nature, 2023). Globally, outdoor (ambient) air pollution is regarded as the second most important cause of lung cancer mortality, and indoor air pollution is considered the seventh most important cause (GBD 2019 Risk Factors Collaborators, Lancet, 2020).
“Recognizing that exposure to air pollution is the second-largest risk factor for lung cancer should be central to discussions within the lung cancer community,” says Joan Schiller, MD, Founder of OUCH-International and long-time member of LCRF’s Board of Directors. “By funding research to better understand the effects of air pollution on the development of lung cancer, we hopefully will enable more effective risk recognition, screening, and education among patients and healthcare professionals.”
“Despite declining rates of tobacco use, the incidence of lung cancer in people with no known risk factors, especially in young women, is on the rise,” remarked Antoinette Wozniak, MD, FASCO, LCRF Chief Scientific Officer. “The more we understand about all major risk factors driving lung cancer, the better equipped we will be to diagnose earlier or even prevent lung cancer from developing.”
Submissions to the Request for Proposals will be accepted until midnight on June 2, 2026. All applications will be subject to rigorous review by LCRF’s Scientific Advisory Board and OUCH-International. More details about the Request for Proposal, along with eligibility, requirements, and deadlines can be found at LCRF.org/FundingOpportunities.
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About the Lung Cancer Research Foundation (LCRF)
The Lung Cancer Research Foundation® (LCRF) is the leading nonprofit organization focused on funding innovative, high-reward research with the potential to extend survival and improve quality of life for people with lung cancer. LCRF’s mission is to improve lung cancer outcomes by funding research for the prevention, diagnosis, treatment, and cure of lung cancer. To date, LCRF has funded 450 research grants, totaling nearly $53 million, the highest amount provided by a nonprofit organization dedicated to funding lung cancer research. For more information about the LCRF grant program and funding opportunities, visit LCRF.org/research.
About Oncology Advocates United for Climate and Health – International (OUCH-I)
OUCH is the only non-profit, nonpartisan volunteer cancer organization focused on mitigating the effects of climate change on cancer care. Our mission is to advance awareness, actions, and policies that mitigate the effects of climate change on cancer care, and our pillars include advocacy, education and outreach research, cancer care delivery, sustainability, and resilience, and climate justice and health equity. Our members include oncology health care professionals (e.g. MDs, PhDs, RNs, pharmacists, social workers, researchers, patient advocates) who are interested in mitigating the effects of climate change on cancer. We currently have over 150 members representing 27 states and 23 different countries, including six oncology professional societies.
Contact:
LUNG CANCER RESEARCH FOUNDATION
Sheila Sullivan
Sr. Director, Marketing & Communications
ssullivan@lcrf.org
OUCH – INTERNATIONAL
Joan H. Schiller, MD
(608) 469-6992
joanhschiller@gmail.com
ouchforclimate.org
