Recent molecular analysis has revealed that L-myc has several domains of extremely conserved anino acid sequence homology with c-myc and N-myc, suggesting similarity of function. We tested the biologic activity of L-myc by using an expression vector containing a cDNA clone coding for the major open reading frame in the 3.9-kilobase mRNA of L-myc under the control of a strong promoter (Moloney long terminal repeat) and found that L-myc complemented an activated ras gene in transforming primary rat embryo fibroblasts. However, the efficiency of transformation was 1 to 10% of that seen with the c-myc and simian virus 40 (SV40) controls. The L-myc/ras transformants initially grew more slowly than c-myc or SV40 transformants, but once established as continuous cell lines, they were indistinguishable from cell lines derived from c-myc/ras or SV40/ras transfectants as determined by morphology, soft-agar cloning, and tumorigenicity in nude mice.

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Under the auspices of the Belgian Society of Medical Oncology (BSMO).Background: New drugs are generally tested in patients with metastatic disease where bulky tumor mass is present. However, antiangiogenic compounds are probably more beneficial in the prevention of regrowth from tumors with small tumor load than in bulky tumors. This study wants to test the hypothesis that antiangiogenic compounds such as sunitinib are able to delay tumor progression after tumor mass reduction by taxanes, i.e. an objective response (PR or CR).Materials and methods: This is a dual-arm open-label randomized multicenter phase II clinical trial with 2:1 randomization evaluating the efficacy of sunitinib (study arm) versus no therapy (control arm, only for descriptive purposes) in patients with metastatic breast cancer after objective response to taxane chemotherapy. Eligible patients had metastatic HER2 negative breast cancer, had received 10 to 20 weeks of first- or second line taxane containing chemotherapy resulting in an objective response (RECIST). Patients received sunitinib (arm A) 50 mg/d po 4w/6 (amended to 37.5 mg continuously in 1-2008) or no therapy (arm B). Patients were stratified for disease free interval and dominant site of disease. Patients randomized to arm B were offered the opportunity to receive open-label sunitinib treatment upon development of disease progression. Treatment was pursued until disease progression or major intolerance or patients refusal. All patients who received at least day 1 of study treatment were evaluated for efficacy, toxicity and safety. The duration of response after taxane treatment in previous studies with metastatic breast cancer is around 7 months. Based on this, the median time interval between the end of chemotherapy and tumor progression was expected to be about 5 months in our study population. The primary endpoint was to determine the proportion of patients alive and without disease progression (PFS) at 5 months after study entry in arm A. If ≤ 18/36 patients are progression-free and alive at 5 months, sunitinib will be declared insufficiently active (beta 0.05); if ≥ 22 patients are progression-free and alive at 5 months, sunitinib will be declared active (alpha 0.05) and it will be recommended to continue the trial as a phase III design.Results: 10/36 patients (28%) reached 5 months PFS in arm A and 4/19 in arm B (21%). Median PFS was 3.4 months in Arm A and 3.1 months in Arm B. Toxicity and overall survival data will be reported at the meeting.Discussion: This study does not confirm the hypothesis that sunitinib can lead to a significant proportion of patients with PFS of ≥ 5 months after objective response to taxanes. This proof-of-principle study suggests that also the role of consolidation therapy with other (already approved) antiangiogenic treatments should be evaluated carefully in prospective clinical trials (high economic cost). Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 203.

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Recent molecular analysis has revealed that L-myc has several domains of extremely conserved amino acid sequence homology with c-myc and N-myc, suggesting similarity of function. We tested the biologic activity of L-myc by using an expression vector containing a cDNA clone coding for the major open reading frame in the 3.9-kilobase mRNA of L-myc under the control of a strong promoter (Moloney long terminal repeat) and found that L-myc complemented an activated ras gene in transforming primary rat embryo fibroblasts. However, the efficiency of transformation was 1 to 10% of that seen with the c-myc and simian virus 40 (SV40) controls. The L-myc/ras transformants initially grew more slowly than c-myc or SV40 transformants, but once established as continuous cell lines, they were indistinguishable from cell lines derived from c-myc/ras or SV40/ras transfectants as determined by morphology, soft-agar cloning, and tumorigenicity in nude mice.