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Biosensors & Bioelectronics Nov 2023Colorectal carcinoma (CRC) is the third most common cancer in terms of diagnosis and the second in terms of mortality. Recent studies have shown that various proteins,... (Review)
Review
Colorectal carcinoma (CRC) is the third most common cancer in terms of diagnosis and the second in terms of mortality. Recent studies have shown that various proteins, extracellular vesicles (i.e., exosomes), specific genetic variants, gene transcripts, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and altered epigenetic patterns, can be used to detect, and assess the prognosis of CRC. Over the last decade, a plethora of conventional methodologies (e.g., polymerase chain reaction [PCR], direct sequencing, enzyme-linked immunosorbent assay [ELISA], microarray, in situ hybridization) as well as advanced analytical methodologies (e.g., microfluidics, electrochemical biosensors, surface-enhanced Raman spectroscopy [SERS]) have been developed for analyzing genetic and epigenetic biomarkers using both optical and non-optical tools. Despite these methodologies, no gold standard detection method has yet been implemented that can analyze CRC with high specificity and sensitivity in an inexpensive, simple, and time-efficient manner. Moreover, until now, no study has critically reviewed the advantages and limitations of these methodologies. Here, an overview of the most used genetic and epigenetic biomarkers for CRC and their detection methods are discussed. Furthermore, a summary of the major biological, technical, and clinical challenges and advantages/limitations of existing techniques is also presented.
Topics: Humans; Biosensing Techniques; Biomarkers; Cell-Free Nucleic Acids; Colorectal Neoplasms; Epigenesis, Genetic
PubMed: 37619478
DOI: 10.1016/j.bios.2023.115611 -
The Oncologist Aug 2023Most gastrointestinal stromal tumors (GIST) are driven by activating mutations in Proto-oncogene c-KIT (KIT) or PDGFRA receptor tyrosine kinases (RTK). The emergence of... (Review)
Review
Most gastrointestinal stromal tumors (GIST) are driven by activating mutations in Proto-oncogene c-KIT (KIT) or PDGFRA receptor tyrosine kinases (RTK). The emergence of effective therapies targeting these mutations has revolutionized the management of advanced GIST. However, following initiation of first-line imatinib, a tyrosine kinase inhibitor (TKI), nearly all patients will develop resistance within 2 years through the emergence of secondary resistance mutations in KIT, typically in the Adenosine Triphosphate (ATP)-binding site or activation loop of the kinase domain. Moreover, some patients have de novo resistance to imatinib, such as those with mutations in PDGFRA exon 18 or those without KIT or PDGFRA mutation. To target resistance, research efforts are primarily focused on developing next-generation inhibitors of KIT and/or PDGFRA, which can inhibit alternate receptor conformations or unique mutations, and compounds that impact complimentary pathogenic processes or epigenetic events. Here, we review the literature on the medical management of high-risk localized and advanced GIST and provide an update on clinical trial approaches to this disease.
Topics: Humans; Imatinib Mesylate; Gastrointestinal Stromal Tumors; Antineoplastic Agents; Piperazines; Pyrimidines; Benzamides; Drug Resistance, Neoplasm; Receptor, Platelet-Derived Growth Factor alpha; Proto-Oncogene Proteins c-kit; Mutation
PubMed: 37315115
DOI: 10.1093/oncolo/oyad167 -
The Journal of Molecular Diagnostics :... Dec 2023As molecularly informed oncology care has increasingly become standard practice for patients with cancer, society must prioritize equitable access to genetic testing...
As molecularly informed oncology care has increasingly become standard practice for patients with cancer, society must prioritize equitable access to genetic testing that guides subsequent care. Despite the availability of genomic testing laboratories, published guidelines, US Food and Drug Administration-approved targeted therapies, financial assistance programs, and clinical decision tools, precision medicine remains out of reach for many patients. While there has been modest improvement in testing rates in recent years, molecular testing and targeted therapy for cancer patients continue to vary by practice setting and patient insurance status, and racial and socioeconomic disparities persist. National standards and centralized solutions are needed to promote the equitable distribution of patient benefit from precision medicine technology. Although various online resources are currently available, no single all-encompassing precision oncology tool currently exists. A one-stop shop to address all aspects of precision oncology-tissue selection and test ordering, interpretation of results, prescribing targeted therapies, and enrolling patients in clinical trials-would disrupt cancer care. Recent advances in artificial intelligence, digital pathology, and data science provide an opportunity for stakeholders to partner together to leverage these technologies to develop this unified, freely accessible, national solution. Whether locoregionally, nationally, or internationally, only collaborative efforts can fully realize the potential of technological advancements in molecular pathology and oncology therapeutics for all cancer patients.
Topics: Humans; Neoplasms; Precision Medicine; Artificial Intelligence; Medical Oncology; Genetic Testing
PubMed: 37748706
DOI: 10.1016/j.jmoldx.2023.09.001 -
Cell Reports Oct 2023The majority of activated ovarian follicles undergo atresia during reproductive life in mammals, and only a small number of follicles are ovulated. Though hormone...
The majority of activated ovarian follicles undergo atresia during reproductive life in mammals, and only a small number of follicles are ovulated. Though hormone treatment has been widely used to promote folliculogenesis, the molecular mechanism behind follicle selection and atresia remains under debate due to inconsistency among investigation models. Using a high-throughput molecular pathology strategy, we depicted a transcriptional atlas of mouse follicular granulosa cells (GCs) under physiological condition and obtained molecular signatures in healthy and atresia GCs during development. Functional results revealed hypoxia-inducible factor 1 (HIF1) as a major effector downstream of follicle-stimulating hormone (FSH), and HIF1 activation is essential for follicle growth. Energy shortage leads to prevalent AMP-activated protein kinase (AMPK) activation and drives follicular atresia. FSHR-mTOR-HIF1 signaling helps follicles escape from the atresia fate, while energy stress persists. Our work provides a comprehensive understanding of the molecular network behind follicle selection and atresia under physiological condition.
Topics: Animals; Female; Mice; AMP-Activated Protein Kinases; Follicular Atresia; Granulosa Cells; Hypoxia-Inducible Factor 1; Mammals; TOR Serine-Threonine Kinases
PubMed: 37733588
DOI: 10.1016/j.celrep.2023.113158 -
Virchows Archiv : An International... Feb 2024The continuing evolution of treatment options in thoracic oncology requires the pathologist to regularly update diagnostic algorithms for management of tumor samples. It... (Review)
Review
The continuing evolution of treatment options in thoracic oncology requires the pathologist to regularly update diagnostic algorithms for management of tumor samples. It is essential to decide on the best way to use tissue biopsies, cytological samples, as well as liquid biopsies to identify the different mandatory predictive biomarkers of lung cancers in a short turnaround time. However, biological resources and laboratory member workforce are limited and may be not sufficient for the increased complexity of molecular pathological analyses and for complementary translational research development. In this context, the surgical pathologist is the only one who makes the decisions whether or not to send specimens to immunohistochemical and molecular pathology platforms. Moreover, the pathologist can rapidly contact the oncologist to obtain a new tissue biopsy and/or a liquid biopsy if he/she considers that the biological material is not sufficient in quantity or quality for assessment of predictive biomarkers. Inadequate control of algorithms and sampling workflow may lead to false negative, inconclusive, and incomplete findings, resulting in inappropriate choice of therapeutic strategy and potentially poor outcome for patients. International guidelines for lung cancer treatment are based on the results of the expression of different proteins and on genomic alterations. These guidelines have been established taking into consideration the best practices to be set up in clinical and molecular pathology laboratories. This review addresses the current predictive biomarkers and algorithms for use in thoracic oncology molecular pathology as well as the central role of the pathologist, notably in the molecular tumor board and her/his participation in the treatment decision-making. The perspectives in this setting will be discussed.
Topics: Female; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pathology, Molecular; Biomarkers, Tumor; Biopsy
PubMed: 37801103
DOI: 10.1007/s00428-023-03651-1 -
Cells Aug 2023Glioblastoma is the most aggressive intracranial tumor [...].
Glioblastoma is the most aggressive intracranial tumor [...].
Topics: Glioblastoma; Humans; Brain Neoplasms; Drug Resistance, Neoplasm
PubMed: 37626873
DOI: 10.3390/cells12162063 -
Pathologie (Heidelberg, Germany) Dec 2023The situation regarding digital pathology in Austria is manageable compared to other countries. Active Austrian examples are the consortium EMPAIA, the private-public... (Review)
Review
The situation regarding digital pathology in Austria is manageable compared to other countries. Active Austrian examples are the consortium EMPAIA, the private-public partnership Bigpicture, the Austrian Society for Clinical Pathology and Molecular Pathology (OEGPath), the company TissueGnostics, and the Austrian Platform for Personalized Medicine (OEPPM).
Topics: Austria; Telepathology; Pathology, Clinical; Pathology, Molecular; Precision Medicine
PubMed: 37987811
DOI: 10.1007/s00292-023-01278-2 -
Cancer Metastasis Reviews Dec 2023Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic cancers in which the site of origin is not identifiable. These carcinomas have a poor outcome... (Review)
Review
Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic cancers in which the site of origin is not identifiable. These carcinomas have a poor outcome due to their late presentation with metastatic disease, difficulty in identifying the origin and delay in treatment. The aim of the pathologist is to broadly classify and subtype the cancer and, where possible, to confirm the likely primary site as this information best predicts patient outcome and guides treatment. In this review, we provide histopathologists with diagnostic practice points which contribute to identifying the primary origin in such cases. We present the current clinical evaluation and management from the point of view of the oncologist. We discuss the role of the pathologist in the diagnostic pathway including the control of pre-analytical conditions, assessment of sample adequacy, diagnosis of cancer including diagnostic pitfalls, and evaluation of prognostic and predictive markers. An integrated diagnostic report is ideal in cases of CUP, with results discussed at a forum such as a molecular tumour board and matched with targeted treatment. This highly specialized evolving area ultimately leads to personalized oncology and potentially improved outcomes for patients.
Topics: Humans; Neoplasms, Unknown Primary; Pathologists; Carcinoma; Prognosis
PubMed: 37394540
DOI: 10.1007/s10555-023-10101-6 -
Diagnostics (Basel, Switzerland) Aug 2023Despite advances in diagnostic imaging, surgical techniques, and systemic therapy, gastric cancer (GC) is the third leading cause of cancer-related death worldwide.... (Review)
Review
Despite advances in diagnostic imaging, surgical techniques, and systemic therapy, gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Unfortunately, molecular heterogeneity and, consequently, acquired resistance in GC are the major causes of failure in the development of biomarker-guided targeted therapies. However, by showing promising survival benefits in some studies, the recent emergence of immunotherapy in GC has had a significant impact on treatment-selectable procedures. Immune checkpoint inhibitors (ICIs), widely indicated in the treatment of several malignancies, target inhibitory receptors on T lymphocytes, including the programmed cell death protein (PD-1)/programmed death-ligand 1 (PD-L1) axis and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and release effector T-cells from negative feedback signals. In this article, we review currently available predictive biomarkers (including PD-L1, microsatellite instability, Epstein-Barr virus, and tumor mutational burden) that affect the ICI treatment response, focusing on PD-L1 expression. We further briefly describe other potential biomarkers or mechanisms for predicting the response to ICIs in GC. This review may facilitate the expansion of the understanding of biomarkers for predicting the response to ICIs and help select the appropriate therapeutic approaches for patients with GC.
PubMed: 37685320
DOI: 10.3390/diagnostics13172782 -
Journal of the American Society of... 2023The International Academy of Cytology has joined with the International Agency for Research on Cancer to bring together a group of experts in lung cytopathology to... (Review)
Review
The International Academy of Cytology has joined with the International Agency for Research on Cancer to bring together a group of experts in lung cytopathology to develop a WHO Reporting System for Lung Cytopathology (WHO System). This System aims to improve and standardize the reporting of cytopathology, facilitate communication between cytopathologists and clinicians, and improve patient care. The WHO System describes 5 categories for reporting lung cytopathology: 'Insufficient/Inadequate/Nondiagnostic', 'Benign', 'Atypical', 'Suspicious for malignancy', and 'Malignant', each one with a clear descriptive term, a definition, a risk of malignancy, and a suggested management algorithm. The key diagnostic cytopathologic features of each of the lesions within each category have been established by consensus through an Expert Editorial Board, who are also the authors of this review and selected for each reporting system and chosen based on their expertise in the field and/or diversity of geographical representation. Many other co-authors from around the world also contributed. The assignment of writing and editing responsibilities used the same model as that used for the WHO Classification of Tumours (https://whobluebooks.iarc.fr/about/faq/). The WHO System provides the best practice application of ancillary testing, including immunocytochemistry and molecular pathology, and guides in sampling and processing techniques to optimize the handling and preparation of specimens. The WHO System was created by the authors to be applicable globally and is based on cytomorphology with possibilities for additional diagnostic management of the patient. The authors are aware that local medical and pathology resources would differ, especially in low- and middle-income countries. The WHO Tumour Classification for Thoracic Tumors, Fifth Edition, is directly accessible through the online WHO System.
Topics: Humans; Biopsy, Fine-Needle; Cytodiagnosis; Patient Care; Lung; World Health Organization
PubMed: 37156705
DOI: 10.1016/j.jasc.2023.04.002