Vecchione et al showed that suppression of RANBP2 results in mitotic defects only in BRAF-like colon cancer (CC) cells, which leads to cell death. Mechanistically, RANBP2 silencing reduces microtubule outgrowth from the kinetochores, thereby inducing spindle perturbations, providing an explanation for the observed mitotic defects. Vinorelbine mimics RANPB2 silencing in BRAF-like and BRAFV600E CC cell lines.
These preclinical data represent a strong rationale to also explore the anti-tumor activity of vinorelbine in patients with advanced BRAF-like (both BRAFm and BRAF wild type) CC. Tumors having this gene signature are referred to as "BRAF-like" and have a similar poor prognosis irrespective of the presence of BRAF(V600E) mutation. Since vinorelbine is standard of care in advanced breast and NSCLC, there is ample experience with the dose and schedule as well as with the safety profile and supportive measures required to prevent side-effects.
Phase:
PHASE2
Details
Lead Sponsor:
The Netherlands Cancer Institute
Collaborators:
Agendia Azienda Ospedaliera Niguarda C Granda Catalan Institute of Health Eli Lilly and Company European Organisation for Research and Treatment of Cancer - EORTC Fundacin para la Investigacin del Hospital Clnico de Valencia Universitaire Ziekenhuizen KU Leuven University of Campania Luigi Vanvitelli University of Turin, Italy Vall d'Hebron Institute of Oncology