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Stimulating the Resolution of Tumor Debris to Control Medulloblastoma
Author(s) -
Barksdale Chantal,
Sulciner Megan,
Ramon Sesquile,
Colas Romain,
Bandopadhayay Pratiti,
Huang Sui,
Kieran Mark,
Serhan Charles,
Panigrahy Dipak
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.147.8
Subject(s) - medulloblastoma , cancer research , medicine , chemotherapy , inflammation , oncology , immunology
Background Tumor recurrence occurs in one‐third of patients with medulloblastoma. Current clinical approaches to reduce medulloblastoma tumor burden, including chemotherapy, may contribute to relapse by creating tumor cell debris. The debris of dead cancer cells can act as a source of tumor stimulation via inflammation. A new direction has emerged in inflammation research with the discovery of endogenous specialized pro‐resolving lipid mediators. We hypothesize that resolvins and protectins represent a novel modality in medulloblastoma treatment by pharmacologically promoting the clearance of tumor debris. Results Flow cytometry confirmed that the chemotherapy cisplatin and the targeted therapy JQ‐1 generated medulloblastoma tumor cell debris. Chemotherapy‐ and targeted therapy‐induced tumor debris stimulated primary tumor growth. Protectins enhanced macrophage phagocytosis of medulloblastoma tumor debris and counter‐regulated secretion of pro‐inflammatory cytokines. Medulloblastoma tumor progression resulted in loss of resolvin levels. Resolvins inhibited medulloblastoma growth at nanogram levels without toxicity. Conclusions Our results demonstrate that enhancing endogenous clearance of tumor debris by resolvins and protectins represents a new biological target for medulloblastoma treatment. Research Support: RO1 01CA170549