Novel Technique For Preclinical Assessment Of Targeted Therapies To Inhibit Both Primary And Metastatic Non-Small Cell Lung Cancer

By Gunisha Arora, Medical and Scientific Writer, Scientific Development

Lung cancer is the leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) accounting for 80% of cases. Brain metastases occur in 20–40% of NSCLC patients and are associated with poor prognosis, high recurrence, and survival of only 1–2 months if untreated. Current treatments — including surgery, radiation, chemotherapy, and immunotherapy — fail to fully address the biology of metastatic progression, highlighting the need for targeted therapies.

EGFR mutations are a major risk factor for brain metastasis in advanced NSCLC. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is now the preferred first-line therapy and has shown improved outcomes when combined with chemotherapy in NSCLC patients with brain metastases.

To enable comprehensive evaluation of therapies targeting both primary and metastatic tumors, Labcorp Discovery Oncology has developed dual-disease xenograft models using bioluminescence imaging (BLI). These models, based on NCI-H1975-Luc and PC-9-Luc-mCh-Puro human NSCLC cell lines with distinct EGFR mutational profiles, allow simultaneous assessment of treatment response in subcutaneous (SC) primary tumors and intracranial (IC) metastases.

In proof-of-concept studies, dual-implanted mice were treated orally with Osimertinib (25 mg/kg QD, 14 days). Tumor growth was monitored by calipers (SC) and BLI (IC), and harvested tumors were analyzed for EGFR and ERK pathway signaling via AlphaLISA™ SureFire Ultra Detection. These results demonstrate the utility of dual-disease models to evaluate targeted therapies for NSCLC with brain metastases.