Low Dose Adjuvant Epigenetic Modifiers Inhibit Cancer Lung Metastases through Disruption of the Myeloid Environment in Pre-metastatic Niches

Unmet Need
Cancer recurrence, even following complete surgical resection, remains a large unmet clinical problem. In non-small cell lung cancer (NSCLC) patients, recurrence following surgery remains 30-70%, and the five-year survival rate remains 23% with over 140,000 deaths occurring each year. Recurrence post-surgery can be driven by a number of factors, including pre-metastatic microenvironment alterations caused by bone marrow-derived myeloid cells. These myeloid cells, myeloid derived suppressor cells (MDSCs), negatively modulate immune responses and can promote tumor progression and metastases. Therefore, MDSCs have emerged as an attractive target for a novel adjuvant therapy for NSCLC. The majority of early stage NSCLC tumors are resected without a neoadjuvant intervention. There is a need to identify adjuvant therapies that can be given following resection in order to decrease metastases and increase disease-free survival.
 
Technology Overview
Johns Hopkins researchers have developed a low-dose adjuvant epigenetic therapy regimen to be used in combination with surgical resection of a primary tumor in NSCLC that reduces pulmonary metastases post-resection by inhibiting trafficking and promoting differentiation of MDSCs. In murine models, the treatment regimen prolongs the disease-free and overall survival time compared to resection alone or resection with adjuvant chemotherapy.
 
Stage of Development
The inventors have completed preclinical testing of the combined therapy regimen in multiple xenograft and allograft mouse models of Lewis Lung Carcinoma (LLC).
 
Publications
None at this time.

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