Mutational profiling using liquid biopsy to guide targeted therapy in patients with metastatic cancer

Liquid biopsy gained significant interest in the area of cancer management. This study aims to evaluate the effectiveness of molecular testing using ctDNA (circulating tumor DNA) to; detect genetic alterations, screen for abnormalities, identify mutations associated with treatment sensitivity or resistance and guide therapy decision for several types of cancer in patients with metastasis. A total of 85 samples were collected from 74 patients recruited at our center, as part of their routine clinical follow-up. 17 different cancer types were analyzed. Genetic testing was conducted in patients with metastasis after failure of standard treatments. Sequencing was conducted in plasma-ctDNA samples; and when it was possible on the tumor tissue as well. Our analysis revealed that 88% (65 patients) of patients were eligible for treatment guidance using liquid biopsy. Among them, 64% (47 patients) received an FDA-approved drug, and treatment decisions were based on molecular testing using ctDNA. Somatic gene mutations were detected in 89% (66 patients) of the patients tested; 81% (60 patients) of patients had at least two mutations, 8% (6 patients) had only one mutation and 11% (8 patients) had no detected mutations. Interestingly, among the genes tested, BRCA2, EGFR, MSH6, and NF1 were the most frequently mutated in our patients. Our study highlights the potential benefits of personalized medicine through a non-invasive genetic testing across patients with metastasis regardless of the cancer types. Moreover, our study identified the frequent occurrence of specific gene mutations across various types of cancer, which paves the way for considering targeted therapies that could be applicable to multiple cancer types, rather than being restricted to just a few.