Abstract
Innovative tumor profiling methodologies are utilized to elucidate the pharmacogenomic landscape of tumor cells in order to support the molecularly guided delivery of therapeutics. Indeed, improved clinical outcomes are achieved in oncology practice by providing the physicians with expert-guided, standardized, and easily interpretable knowledge, translated from molecular profiling analysis to support clinical decision-making. However, there is still limited utilization of the technology especially in small private oncology practices. In this work, we analyzed how molecularly guided interventions in 17 consented cancer patients led to an overall improvement of disease response rates in a private oncology center. The precision medicine strategy was based on the OncoDEEP™ profiling solutions and focused on finding clinically actionable relationships between tumor biomarkers and drug responses. The obtained data support the notion that (a) following the pharmacogenomic-derived recommendations favorably impacted cancer therapy progression, and (b) the earlier profiling followed by the delivery of molecularly targeted therapy led to more durable and improved pharmacological response rates. Moreover, we report the example of a patient with metastatic gastric adenocarcinoma who, based on the molecular profiling data, received an off-label therapy that resulted in a complete response and a current cancer-free maintenance status. Overall, our data provide a paradigm on how molecular tumor profiling can improve decision-making in the routine private oncology practice.
Highlights
Recent statistical studies concerning the incidence of malignancies propose that despite the clinical success obtained during the previous years, cancer is expected to be the leading cause barrier of increasing life expectancy in the 21st century [1, 2]
In a typical screening of such type, multiple genes and proteins implicated in tumor initiation, progression, and drug resistance are analyzed in tumor biopsies in order to identify potential alterations that may aid in therapy decision
At the protein level, p4E-BP1 and ERCC1 were found to be frequently upregulated (Supplementary Figure 2). These findings suggest that those patients may receive mammalian target of rapamycin inhibitors, but they should avoid a platinum-based chemotherapy due to ERCC1 overactivation, which would undermine the therapeutic outcome
Summary
Recent statistical studies concerning the incidence of malignancies propose that despite the clinical success obtained during the previous years, cancer is expected to be the leading cause barrier of increasing life expectancy in the 21st century [1, 2] This is, at least partially, attributed to the fact that cancer therapies are still applied on an experience-based manner and often without taking into consideration the special genomic and proteomic landscape of the tumor. The success of the technology has already been demonstrated for various combinations of altered biomarkers and therapeutic molecules, such as epidermal growth factor receptor (EGFR) expression and EGFR tyrosine kinase inhibitors/antibodies, or the expression of programmed death ligand 1 (PD-L1) with anti-PD1 and anti-PD-L1 therapies This way, clinicians obtain a personalized therapeutic overview, which assists them to decide on the potential: (a) clinical benefit, (b) inefficacy, and (c) toxicity of a treatment. They are informed on the potential utility of a drug with an off-label indication or about treatments that are under investigation in ongoing clinical trials
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