Gene Expression Profiling of Tumors From Heavily Pretreated Patients With Metastatic Cancer for the Selection of Therapy: A Pilot Study

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Abstract

Background:

Recently, it has been shown that it is possible to identify tumor profiles of sensitivity for potentially useful drugs, both conventional and experimental, based on whole oligonucleotide microarray gene expression studies in heavily pretreated patients with metastatic solid tumors.

Methods:

Fresh-frozen tumor biopsies for molecular profiling (MP) were obtained from patients with advanced and refractory cancer. Total tumor and control tissue RNA was hybridized to a whole human genome oligonucleotide microarray. Differentially expressed genes interacting with potential therapeutic targets were identified. Results were complemented with DNA sequencing of selected driver genes and with immunohistochemistry and fluorescent “in situ” hybridization. The results were used to guide experimental treatment.

Results:

MP assays led to a potentially active available drug in 91.2% of the patients. The median number of available active drugs per tumor was 5 (range, 1 to 9). Nine treated patients were not evaluable for response. Partial response was observed in 18 patients (33%), stable disease in 22 patients (40%) (clinical benefit rate of 73%), and progression in 15 (27%). Overall median progression-free survival and overall survival were 8 and 13 months, respectively.

Conclusion:

MP-guided therapy is feasible and seems to improve the clinical outcome of extensively pretreated patients but prospective and confirmatory trials are needed.

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