Evaluation of blood MSI burden dynamics to trace immune checkpoint inhibitor therapy efficacy through the course of treatment.

Analysis of serial liquid biopsy (LB) samples has been found to be a promising approach for the monitoring of tumor dynamics in the course of therapy for patients with colorectal cancer (CRC). Currently, somatic mutations are used for tracing the dynamics of the tumor via LB. However, the analysis of the dynamic changes in the molecular signatures such as microsatellite instability (MSI) is not currently used.

Multi-Institutional Evaluation of Interrater Agreement of Biomarker-Drug Pair Rankings Based on the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) and Sources of Discordance.

Background: The widespread use of next-generation sequencing in clinical practice has contributed to the accumulation of a large number of genomic findings associated with targeted therapy; therefore, the problem of ranking the detected findings has become acute. The European Society for Medical Oncology Scale of Clinical Actionability of molecular Targets (ESCAT) system was designed by the European Society for Medical Oncology to rank biomarkers into levels of evidence that reflect their potency and clinical significance based on published clinical data. However, the ESCAT system remains imperfect, as it is based on a subjective assessment of the levels of evidence.

Untapped Potential of Poly(ADP-Ribose) Polymerase Inhibitors: Lessons Learned From the Real-World Clinical Homologous Recombination Repair Mutation Testing.

Background: Testing for homologous recombination deficiency (HRD) mutations is pivotal to assess individual risk, to proact preventive measures in healthy carriers and to tailor treatments for cancer patients. Increasing prominence of poly(ADP-ribose) polymerase (PARP) inhibitors with remarkable impact on molecular-selected patient survival across diverse nosologies, ingrains testing for BRCA genes and beyond in clinical practice. Nevertheless, testing strategies remain a question of debate.

Evidence blocks for effective presentation of genomic findings at molecular tumor boards: Single institution experience.

Genomic profiling, or molecular profiling of the tumor, is becoming a key component of therapeutic decision making in clinical oncology, and is typically carried out via next generation sequencing. However, the interpretation of the results and evaluation of rationale for targeting the uncovered alterations is challenging and requires a deep understanding of cancer biology, genetics, genomics and oncology. Multidisciplinary molecular tumor boards represent a promising strategy in the facilitation of molecularly-informed therapeutic decisions, and usually consist of specialists with various fields of expertise.

Microsatellite Instability: A Review of Molecular Epidemiology and Implications for Immune Checkpoint Inhibitor Therapy.

Microsatellite instability (MSI) is one of the most important molecular characteristics of a tumor, which occurs among various tumor types. In this review article, we examine the molecular characteristics of MSI tumors, both sporadic and Lynch-associated. We also overview the risks of developing hereditary forms of cancer and potential mechanisms of tumor development in patients with Lynch syndrome.

Utility of public knowledge bases for the interpretation of comprehensive tumor molecular profiling results.

With the growing use of comprehensive tumor molecular profiling (CTMP), the therapeutic landscape of cancer is rapidly evolving. NGS produces large amounts of genomic data requiring complex analysis and subsequent interpretation. We sought to determine the utility of publicly available knowledge bases (KB) for the interpretation of the cancer mutational profile in clinical practice.

Transcriptomic Signatures in Colorectal Cancer Progression.

Aims: Due to a large number of identified hub-genes encoding key molecular regulators, which are involved in signal transduction and metabolic pathways in cancers, it is relevant to systemize and update these findings.

Background: Colorectal cancer (CRC) is the third leading cause of cancer death in the world, with high metastatic potential. Elucidating the pathogenic mechanisms and selection of novel biomarkers in CRC is of great clinical significance.