Open AccessSYST-02. DUAL INHIBITION OF BCL-2 AND EGFR IN A PRECLINICAL MODEL OF LUNG CANCER BRAIN METASTASIS
Author(s) -
Kathryn E. Blethen,
Samuel A. Sprowls,
Tasneem Arsiwala,
Ross Fladeland,
Dhruvi Panchal,
Neal Shah,
Brooke Kielkowski,
Weimin Gao,
Paul R. Lockman
Publication year - 2021
Publication title -
neuro-oncology advances
Language(s) - English
Resource type - Journals
ISSN - 2632-2498
DOI - 10.1093/noajnl/vdab112.030
Subject(s) - lung cancer , gefitinib , brain metastasis , epidermal growth factor receptor , medicine , erlotinib , egfr inhibitors , cancer research , cancer , malignancy , metastasis , oncology , tyrosine kinase inhibitor , lung
Lung cancer is the most prevalent malignancy to affect both men and women. Around 80% of all lung cancers are classified as non-small cell lung cancer (NSCLC). This subtype of lung cancer is also the most likely to metastasize to the brain. Clinically, the common treatment for NSCLC is epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), due to the high occurrence of EGFR mutations. However, the cancer cells quickly develop resistance to the EGFR TKIs. This resistance and the added difficulty of delivering drugs across the blood-tumor barrier in efficacious concentrations to treat brain lesions are important to consider when developing treatment strategies for lung cancer brain metastases. Our study utilizes a NSCLC cell line, PC-9-Br6, which was developed in our laboratory to preferentially metastasize to the brain. This cell line was demonstrated by our collaborator to express higher levels of Bcl-2 in comparison to the parental PC-9-P cell line. We hypothesized combining novel Bcl-2 inhibitors (ABT-199/ABT-263) with an EGFR inhibitor (gefitinib) would increase survival and decrease tumor burden in our clinically relevant mouse model of lung cancer brain metastases.