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.
Name: Vinorelbine TartrateDescription: Intravenous administration of vinorelbine on day 1 and day 8 in a dose of 30 mg/m2. One treatment cycle is 21 days.Type: Drug
Cohort A; KRASmt, BRAFwt, BRAF-like CC Cohort B; KRASwt, BRAFmt, BRAF-like CC
Description: This means that by vinorelbine treatment the rate of progression drops to 25%.Measure: Doubling of progression free survival Time: 15 months
Description: The molecular status will be measured by NGS and IHC in tumor tissue.Measure: Baseline molecular status (mutation/ expression) in tumor tissue of potential predictive markers of tumor response Time: 15 months
Description: The molecular status will be measured by NGS and IHC in tumor tissue.Measure: Gene alterations/expression profiles (i.e. baseline, relapse) in tumor tissue upon progression Time: 15 months
There is one SNP
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. --- V600E ---