The Addario Lung Cancer Medical Institute (ALCMI), Champions Oncology and EGFR Resisters have announced the launch of a new study to create a novel bank of patient derived xenograft (PDX) models to help researchers better understand why patients living with Epidermal Growth Factor Receptor (EGFR) positive lung cancer develop resistance to treatment over time, or do not respond at all.
The brain-child of two patient-driven organizations, the Addario Lung Cancer Foundation (one of the largest international philanthropies devoted exclusively to eradicating lung cancer through research, early detection, education and treatment), and the EGFR Resisters (a grassroots, patient-driven community dedicated exclusively to changing EGFR-positive lung cancer into a manageable chronic disease), this study is a collaboration with leading lung cancer researcher and pioneer in EGFR mutant lung cancer, Pasi A. Jänne, MD, PhD of Dana-Farber Cancer Institute and Champions Oncology and is powered by Addario Lung Cancer Medical Institute.
Epidermal growth factor receptor (EGFR) is a trans-membrane glycoprotein with an extracellular epidermal growth factor binding domain and an intracellular tyrosine kinase domain that regulates signaling pathways to control cellular proliferation. EGFR mutations, initially reported in 2004, are currently defined as the most prevalent actionable genomically classified subgroup of NSCLC, which account for 40% of Asian patients and 10-15% of White or African American patients.
Non-small cell lung cancer in turn, makes up 10 to 15% of patients in the United States and about 50% of young adults with lung cancer.
Variations of EGFR gene mutations
There are many variations of EGFR gene mutations.
Some EGFR patients with specific genetic markers (L858R, T790M, exon 19 deletion) respond well to targeted therapies initially, but later develop resistance to treatment. To date, there are no known effective therapies for patients with one rare EGFR mutation (exon 20 insertion).
The purpose of this study is to develop a resource of EGFR mutant cancer models to help drive research in this difficult disease.
Central nervous system metastases
Central nervous system (CNS) metastases including brain metastasis are associated with poor prognosis in non-small cell lung cancer. The median overall survival (OS) for patients with brain metastasis is around 16 months. In these cases whole brain radiotherapy, stereotactic radiosurgery, or surgery is widely used to treat brain metastasis.
Overall, the treatment of CNS metastases requires a multidisciplinary approach. Unfortunately, many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood-brain barrier (BBB), creating a major unmet need for the development of agents with good BBB-penetrating biopharmaceutical properties. With this new study, researchers hope to change that.
“I’m pleased to be part of a collaborative effort that will help researchers move faster toward finding effective lung cancer treatments,” said Teri Kennedy, an EGFR-positive lung cancer patient and one of the founders of EGFR Resisters.
“As a lung cancer patient and a friend of many other lung cancer patients and their families, I know firsthand how heartbreaking it is to develop resistance to treatment. This grassroots, patient-driven community hopes to empower patients to participate to find cures and work with researchers to advance research.”
The ALCMI-012 study is a prospective biospecimen collection study from patients with EGFR mutant tumors. As part of the study, researchers will collect a small amount of tumor or pleural fluid from patients who require biopsies or surgery for medical reasons and agree to donate a portion of their tumor.
Champions will develop these EGFR PDX models by injecting a piece of the donated tumor or pleural fluid (from around a patient’s lungs) into a special type of mouse that has a limited immune system. Research has shown that tumors grown in these ‘host’ mice retain features similar to the patient’s original tumor. Most importantly, these models will be available to researchers worldwide through ALCMI.
“This study provides an opportunity to change EGFR positive lung cancer into a manageable, chronic disease,” said Pasi Jänne, M.D., Ph.D. the study’s lead investigator.
“It’s my hope that every patient diagnosed with a resistant EGFR mutation will take part and help speed the progress toward lasting treatments,” Jänne added.
The study, currently open to patients in the U.S. and Canada, is powered by Addario Lung Cancer Medical Institute’s remote study capabilities. There is no need to travel to another institution to participate in this study.
“We are pleased to offer patients living anywhere in the US and Canada an opportunity to positively impact research in their disease by participating in this study. Our team is available to the patient and physician community to answer questions and to support your participation” said Tony Addario, chair and CEO of the Addario Lung Cancer Medical Institute (ALCMI).
“Champions Oncology is pleased to collaborate in this patient-driven initiative that will advance research for patients with EGFR gene mutations. The team’s shared scientific goals, expertise and commitment ensures that we will engage the patient community to understand the genomics of EGFR and can work with researchers to develop better treatments,” said Jennifer Jaskowiak, director, strategic alliances and partnerships at Champions Oncology.
 Fan Y, Xu X, Xie C. EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data. Onco Targets Ther 2014; 7: 2075-84.
[2 ]Ahluwalia MS, Becker K, Levy BP.Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Central Nervous System Metastases from Non-Small Cell Lung Cancer. Oncologist. 2018 Oct;23(10):1199-1209. doi: 10.1634/theoncologist.2017-0572. Epub 2018 Apr 12.
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