Expert review of molecular diagnostics
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Expert Rev. Mol. Diagn. · Oct 2017
ReviewAn update on biomarkers for kinase inhibitor response in non-small-cell lung cancer.
The discovery of activating genetic and their use as predictive biomarkers for targeted therapy, such as tyrosine kinase inhibitors (TKIs), has changed the treatment paradigm of non-small cell lung cancer (NSCLC). As a result, epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) TKIs have become the standard first-line treatment. Since then, other kinds of targetable oncogenic alterations have been identified in NSCLC. ⋯ Expert commentary: Although targeted therapies dramatically improve the outcome of patients with NSCLC harboring specific oncogenic alterations, molecular and clinical resistance almost invariably develops. New TKIs specifically active in molecular subgroups of NSCLC or the resistance setting have now been developed. The development of additional TKIs and rational combinations may further improve outcomes of NSCLC.
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Expert Rev. Mol. Diagn. · Jun 2017
ReviewOverview of procalcitonin assays and procalcitonin-guided protocols for the management of patients with infections and sepsis.
Procalcitonin is a surrogate infection blood marker whose levels help estimate the likelihood of bacterial infections and correlate with their resolution. Recent trials have revealed the benefits of inclusion of procalcitonin in antibiotic stewardship protocols for initiation and discontinuation of antimicrobial therapy. Areas covered: Procalcitonin-guided antibiotic stewardship protocols have shown appreciable reductions in antibiotic use and duration of therapy in respiratory infections, sepsis, and other infections, with positive effects on clinical outcomes. ⋯ The authors provide an overview of the strengths and limitations of currently available procalcitonin assays and antibiotic therapy algorithms incorporating procalcitonin currently used in different clinical settings and in patients with different underlying infections. Expert commentary: Use of sensitive procalcitonin measurements in clinical algorithms can reduce antimicrobial overuse, decreasing the risk of side effects and controlling emerging bacterial multi-resistance. Before use in clinical practice, it is important to carefully assess the quality of novel PCT assays and rigorously evaluate them in target patient populations across clinically relevant cut-off ranges.
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Next-generation sequencing and advances in 'omics technology have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers. Areas covered: Once characterized only by histologic appearance and clinical behavior, we now understand many of the molecular phenotypes that underlie the different ovarian cancer subtypes. While the current approach to treatment involves standard cytotoxic therapies after cytoreductive surgery for all ovarian cancers regardless of histologic or molecular characteristics, focus has shifted beyond a 'one size fits all' approach to ovarian cancer. Expert commentary: Genomic profiling offers potentially 'actionable' opportunities for development of targeted therapies and a more individualized approach to treatment with concomitant improved outcomes and decreased toxicity.
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Expert Rev. Mol. Diagn. · Sep 2016
ReviewManagement of high-risk HPV-positive women for detection of cervical (pre)cancer.
Primary HPV-testing has been shown to provide a superior detection of women at risk of cervical (pre)cancer compared to cytology-based screening. However, as most high-risk HPV infections are harmless, additional triage testing of HPV-positive women is necessary to identify those with cervical (pre)cancer. In this paper, we compare the performance, advantages and limitations of clinically relevant available triage strategies for HPV-positive women. ⋯ Many different colposcopy triage strategies, comprising both microscopy-based and molecular (virus/host-related) markers, have been suggested: Pap cytology, p16/Ki-67 dual-stained cytology, HPV16/18 genotyping, viral DNA methylation and host cell DNA methylation. Literature search was limited to triage strategies that have achieved at least phase 2 of the five-phase framework for biomarker development and studies including large cohorts (≥100 hrHPV-positive women). Triage markers were stratified by sample type (cervical scrape, self-collected sample) and by study population (screening, non-attendee, referral). Expert commentary: At present, repeat Pap cytology and Pap cytology combined with HPV16/18 genotyping are the only triage strategies that have been robustly shown to be ready for implementation. Other strategies such as p16/Ki-67 dual-stained cytology and host cell DNA methylation analysis, with or without additional HPV16/18 genotyping, are attractive options for the near future.
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Expert Rev. Mol. Diagn. · Jan 2016
ReviewLung cancer screening: utility of molecular applications in conjunction with low-dose computed tomography guidelines.
Finding early-stage lung cancer where there is a higher chance for patient survival remains a major healthcare challenge. Low-dose spiral computed tomography for high-risk patients can increase the detection of cancers with certain tradeoffs, such as increased radiation exposure and surgical risks for false-positive cases. New molecular markers and assays show considerable promise to further reduce healthcare costs and improve lung cancer survival rates but require further validation. This review summarizes and discusses the current state of research in lung cancer screening and highlights developments in biomarker research for lung cancer diagnostics.