0000000000423998
AUTHOR
Marina Sekacheva
Molecular pathway activation – New type of biomarkers for tumor morphology and personalized selection of target drugs
Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in cancer development and progression, being deeply implicated in intracellular signaling pathways. To date, hundreds of different ATDs were approved for clinical use in the different countries. Compared to previous chemotherapy treatments, ATDs often demonstrate reduced side effects and increased efficiency, but also have higher costs. However, the efficiency of ATDs for the advanced stage tumors is still insufficient. Different ATDs have different mechanisms of action and are effective in different cohorts of patients. Personalized approaches are therefore needed to select the best ATD…
Oncobox, gene expression-based second opinion system for predicting response to treatment in advanced solid tumors.
e13143 Background: Anticancer Targeted Drugs (ATDs) specifically target one or a few types of tumor-related molecules in a cell. More than two hundred of ATDs were approved worldwide. They have different mechanisms of action and are effective for different cohorts of patients. However, many individual cases remain poorly responsive and it is of great importance to identify predictive markers of ATD efficacy. Our aim was to develop a platform enabling smart selection of the most efficient ATD therapies. Methods: We generated a second-opinion platform for clinical oncologists termed Oncobox. It is based on the analysis of gene expression profile of a cancer sample in comparison with the corr…
Disparity between Inter-Patient Molecular Heterogeneity and Repertoires of Target Drugs Used for Different Types of Cancer in Clinical Oncology
Inter-patient molecular heterogeneity is the major declared driver of an expanding variety of anticancer drugs and personalizing their prescriptions. Here, we compared interpatient molecular heterogeneities of tumors and repertoires of drugs or their molecular targets currently in use in clinical oncology. We estimated molecular heterogeneity using genomic (whole exome sequencing) and transcriptomic (RNA sequencing) data for 4890 tumors taken from The Cancer Genome Atlas database. For thirteen major cancer types, we compared heterogeneities at the levels of mutations and gene expression with the repertoires of targeted therapeutics and their molecular targets accepted by the current guideli…
Clinical use of RNA sequencing and oncobox analytics to predict personalized targeted therapeutic efficacy.
e13676 Background: Analysis of mutation profiles in cancer patients does not provide clinical benefits in 80-90% of cases in the US (Marquart et al., 2018). Gene expression analysis potentially complements standard detection of clinically relevant mutations. Methods: 239 adult late-stage cancer patients. RNA gene expression sequencing completed on solid tumor samples using FFPE blocks. Patient mRNA profiles were analyzed using Oncobox bioinformatics, prioritizing target drugs according to their personalized predicted efficacy. Summary reports were provided to oncologists and resulting treatment selection and outcomes were assessed. Results: As of February 2020, feedback was received from p…
RNA sequencing for research and diagnostics in clinical oncology.
Molecular diagnostics is becoming one of the major drivers of personalized oncology. With hundreds of different approved anticancer drugs and regimens of their administration, selecting the proper treatment for a patient is at least nontrivial task. This is especially sound for the cases of recurrent and metastatic cancers where the standard lines of therapy failed. Recent trials demonstrated that mutation assays have a strong limitation in personalized selection of therapeutics, consequently, most of the drugs cannot be ranked and only a small percentage of patients can benefit from the screening. Other approaches are, therefore, needed to address a problem of finding proper targeted thera…