Neoplasia
C. Simon Herrington in Muir's Textbook of Pathology, 2020
Molecular pathology (or molecular diagnostics) involves testing tumour-derived nucleic acids or proteins for single or multiple genetic or molecular changes that can be used to inform management or treatment decisions. A common example is testing breast cancers for either HER2 amplification (by fluorescence in-situ hybridization on tumour tissue sections) and/or HER2 protein overexpression (by immunohistochemistry), to advise use of the monoclonal antibody therapy Trastuzumab (Herceptin), an antibody that binds and blocks HER2 protein function, and this is effective in HER2+ breast cancers. In chronic myeloid leukaemia, detection of the Philadelphia chromosome translocation, t(9;22), a reciprocal chromosome translocation that fuses together parts of the BCR gene on chromosome 9 with the ABL gene on chromosome 22, to generate a chimaeric BCR–ABL protein with a deregulated tyrosine kinase activity in leukaemic cells. If detected, this permits treatment with Imatinib (Glivec) a small molecule inhibitor of the tyrosine kinase enzymic activity of the BCR–ABL protein. Common molecular pathology tests used on tumours are listed in Table 6.16.
Pathology in the Era of Personalized Medicine
II-Jin Kim in Cancer Genetics and Genomics for Personalized Medicine, 2017
To manage cancer patients in daily practice, all that had been required of pathologists was an accurate and timely pathologic diagnosis. However, since our understanding of the genetic changes that lead to carcinogenesis, cancer progression, and metastasis has improved [1] and targeted therapies based on these genetic events have been developed for various cancers [2], the focus has shifted towards the use of molecular analyses to identify patients that are most likely to respond to these therapies. Therefore, in addition to accurate and timely diagnoses, complete reporting that can guide patient management is needed from pathologists, and as such, they will play an integral role in personalized medicine. In this chapter, the role and clinical significance of molecular pathology in personalized medicine are covered.
What Is Molecular and Cellular Imaging?
Michel M. J. Modo, Jeff W. M. Bulte in Molecular and Cellular MR Imaging, 2007
Developments in molecular and cellular imaging will allow the investigation of the elemental constituents of organs, and hence introduce a means to interrogate everything from gene expression to functional circuitries. The ability to link behavior to functional connectivity in the brain and tease out the molecular and anatomical changes underlying the changes through molecular imaging15 will truly provide a powerful integration of different organizational levels from gene expression to its effect on behavior. As disease-related symptoms are but a modification of normal behavior, it is potentially possible to move beyond symptom-based diagnosis and focus on the specific underlying molecular changes. Although many medical disciplines already base their diagnosis on molecular pathology, this is mainly the case for easily accessible organs, such as the skin, and currently cannot be used for diseases pertaining to the brain or heart. It is therefore likely that medical disciplines concerned with internal organs will have the most to gain from molecular and cellular imaging, and at the same time are likely to see more change in clinical practice than existing approaches.16 Molecular medicine will not only lead to earlier diagnosis and treatment, but also might redraw the definition of what we consider a disease. However, these predictions and promises are largely dependent on the advances and limits of technological developments in imaging.9,17–20
Benign ependymoma with extensive intracranial and spinal cerebrospinal fluid dissemination: case report and literature review
Published in British Journal of Neurosurgery, 2019
Fangmei Zhu, Jurong Ding, Yumei Li, Dewang Mao, Xianglei He, Wanyuan Chen, Lin Lou, Zhongxiang Ding
Currently, the trend in glioma classification has favored molecular diagnosis. Molecular pathology is playing an increasingly important role in daily practice to meet the needs of individualized diagnosis and treatment guidance. As a consequence of chromosomal translocation, LOH 1p/19q status implies that the pathological classification should be that of oligodendroglioma, which is characterized by a prolonged survival time and sensitivity to chemoradiotherapy.21 Mutation of the IDH1 or IDH2 gene is mostly observed in a low-grade glioma or a secondary high-grade glioma that develops from a lower-grade glioma. An IDH-mutated tumor tends to have a better prognosis than the same non-mutated subtype. Conjointly analyzing TERT and the mutation of IDH in glioma subtypes contributes to glioma classification and prognosis.22 In our case, the results of molecular pathology are negative, which suggest that this case is not a oligodendroglioma and that the patient may not have benefitted from chemotherapy with an alkylating agent such as temozolomide.
Site-agnostic biomarker-guided oncology drug development
Published in Expert Review of Molecular Diagnostics, 2020
For decades, cancers have been classified according to the organ from where the tumor arises. The thinking behind this classification was that the origin of the tumor was closely linked to the biological behavior and hence this characteristic could be used to guide the selection of an optimal therapy [1]. However, in most cases, this shown not to be the case and the past decades have taught us that cancer is a group of very heterogeneous diseases where complex molecular mechanisms play a key role. The development within molecular diagnostics has enabled us to study these mechanisms and have fostered a greater understanding of the molecular pathology and what drives the diseases. This increased molecular understanding has slowly changed the way that cancers are classified and the way that anticancer drugs are developed. Many cancer diseases can now be divided into subgroups based on molecular characteristics, and an increasing number of drugs are being developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. Not only do these biomarker assays support the development process they are also an important treatment decision tool in relation to the use of the drugs after regulatory approval. When such a predictive assay is linked to a specific drug it is called a companion diagnostic (CDx) [2].
Intellectual property considerations for molecular diagnostic development with emphasis on companion diagnostics
Published in Expert Opinion on Therapeutic Patents, 2018
Harry Glorikian, Richard Jeremy Warburg, Kelly Moore, Jennifer Malinowski
Molecular diagnostics, including companion diagnostics, are the integral component required for precision medicine, which is enabled by molecular pathology epidemiology. A multidisciplinary field, molecular pathology epidemiology encompasses public health/epidemiology, drug discovery and design, computational biology, and bioinformatics [14,15]. As scientific researchers identify biomarkers (e.g. DNA, RNA, proteins) associated with disease states and/or clinical outcomes, the role of molecular diagnostics increases. In oncology, for example, diagnostics are routinely used to classify cancer patients for prognosis and treatment regimens[16]. Many hospitals and medical centers, including the National Institutes of Health Clinical Center, are using diagnostics to proactively identify patients who are at risk for adverse drug interactions and for dosing certain medications, such as blood thinners [17]. Therefore, the role of molecular diagnostics, and specifically companion diagnostics, in the implementation of precision medicine cannot be overstated.
Related Knowledge Centers
- Biochemistry
- DNA Microarray
- In Situ Hybridization
- Molecular Biology
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- Polymerase Chain Reaction
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- Pathology
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- Real-Time Polymerase Chain Reaction