Begell House Inc.
Critical Reviews™ in Oncogenesis
CRO
0893-9675
22
5-6
2017
Preface: Genomic Pathology and Cancer Biomarkers: Toward Precision Medicine
v-vi
10.1615/CritRevOncog.2017021230
Liang
Cheng
Departments of Pathology, Indiana University School of Medicine, Indianapolis, USA;
Department of Urology, Indiana University School of Medicine, Indianapolis, USA; Molecular PathologyDepartment of Pathology and Laboratory MedicineWarren Alpert
Medical School of Brown University | LifespanAcademic Medical CenterAssociate
Director for Shared ResourcesLegorreta CancerCenter at Brown University
Qiu
Rao
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Xiao-Tong
Wang
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Bo
Zhang
Department of Pathology
Health Science Center of Peking University
Beijing, China
Rodolfo
Montironi
Institute of Pathological Anatomy and
Histopathology Polytechnic University of the Marche Region (Ancona) and United Hospitals
Ancona, Italy
None
Prostate Cancer Biomarkers: Current Status
253-269
10.1615/CritRevOncog.2017020500
Kurt B.
Hodges
Department of Pathology & Laboratory Medicine, University of Kentucky, Lexington, Kentucky
Emily
Bachert
Department of Pathology & Laboratory Medicine, University of Kentucky, Lexington, Kentucky
Liang
Cheng
Departments of Pathology, Indiana University School of Medicine, Indianapolis, USA;
Department of Urology, Indiana University School of Medicine, Indianapolis, USA; Molecular PathologyDepartment of Pathology and Laboratory MedicineWarren Alpert
Medical School of Brown University | LifespanAcademic Medical CenterAssociate
Director for Shared ResourcesLegorreta CancerCenter at Brown University
prostate cancer
gene panel
RNA
DNA
proteomics
metabolomics
epigenetic signature
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men worldwide. Given the biological heterogeneity in localized PCa and its variable clinical course, a personalized approach to patient risk stratification and management is needed. A variety of high-throughput technologies, such as next-generation
sequencing, transcriptomic, epigenetic, and metabolomic modalities have led to an improved understanding of the
genomic basis of PCa and the identification of PCa biomarkers. Novel genomic approaches offer additional information to improve clinical decision making. The goal of this report is to review the use of currently available molecular biomarkers in the diagnosis and prognostication of PCa outcome.
Emerging Concepts and Methodologies in Cancer Biomarker Discovery
371-388
10.1615/CritRevOncog.2017020626
Meixia
Lu
Department of Epidemiology and Biostatistics, and The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Jinxiang
Zhang
Department of Surgery, Wuhan Union Hospital, and Tongji Medical College, Huazhong University of
Science and Technology, Wuhan, Hubei, China
Lanjing
Zhang
Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ, USA; Department of Biological Sciences, Faculty of Arts and Sciences, Rutgers University, Newark,
NJ, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA; Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA
cancer biomarker
open access data
TCGA
GEO and rare diseases
Cancer biomarker discovery is a critical part of cancer prevention and treatment. Despite the decades of effort, only a small number of cancer biomarkers have been identified for and validated in clinical settings. Conceptual and methodological breakthroughs may help accelerate the discovery of additional cancer biomarkers, particularly their use for diagnostics. In this review, we have attempted to review the emerging concepts in cancer biomarker discovery, including real-world evidence, open access data, and data paucity in rare or uncommon cancers. We have also summarized the recent methodological progress in cancer biomarker discovery, such as high-throughput sequencing, liquid biopsy, big data, artificial intelligence (AI), and deep learning and neural networks. Much attention has been given to the methodological details and comparison of the methodologies. Notably, these concepts and methodologies interact with each other and will likely lead to synergistic effects when carefully combined. Newer, more innovative concepts and methodologies are emerging as the current emerging ones became mainstream and widely applied to the field. Some future challenges are also discussed. This review contributes to the development of future theoretical frameworks and technologies in cancer biomarker discovery and will contribute to the discovery of more useful cancer biomarkers.
Liquid Biopsies in the Management of Bladder Cancer: Next-Generation Biomarkers for Diagnosis, Surveillance, and Treatment-Response Prediction
389-401
10.1615/CritRevOncog.2017020803
Yu
Yang
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA
Catherine R.
Miller
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA
Antonio
Lopez-Beltran
Department of Pathology and Surgery, Faculty of Medicine, Cordoba, Spain and Champalimaud Clinical Center, Lisbon, Portugal
Rodolfo
Montironi
Institute of Pathological Anatomy and
Histopathology Polytechnic University of the Marche Region (Ancona) and United Hospitals
Ancona, Italy
Monica
Cheng
Departments of Pathology, Indiana University School of Medicine, Indianapolis, USA
Shaobo
Zhang
Departments of Pathology, Indiana University School of Medicine, Indianapolis, USA
Michael O.
Koch
Department of Urology, Indiana University School of Medicine, Indianapolis, USA
Hristos Z.
Kaimakliotis
Department of Urology, Indiana University School of Medicine, Indianapolis, USA
Liang
Cheng
Departments of Pathology, Indiana University School of Medicine, Indianapolis, USA;
Department of Urology, Indiana University School of Medicine, Indianapolis, USA; Molecular PathologyDepartment of Pathology and Laboratory MedicineWarren Alpert
Medical School of Brown University | LifespanAcademic Medical CenterAssociate
Director for Shared ResourcesLegorreta CancerCenter at Brown University
liquid biopsy; bladder; biomarker; circulating tumor cells; cell-free tumor DNA
In this review, we discuss the types of liquid biopsies currently available, and their recent and potential clinical applications, especially as they relate to the detection of molecular biomarkers of bladder cancer. The advances in research using high-throughput next-generation genomic techniques have identified a number of promising molecular biomarkers of bladder urothelial carcinoma. Liquid biopsy has recently received enormous attention as a potential tool for real-time monitoring of disease status in cancer patients, and genomic profiles are reported to closely match those of corresponding tumors. It is noninvasive and easily repeated, and allows monitoring during treatment and detection of different genomic alterations that are potentially accessible to targeted therapy or are associated with treatment resistance in bladder cancer patients. Moreover, liquid biopsy is a tool that allows rapid access to biomarker assessment in patients for whom solid biopsies are not available. Liquid biopsy will be widely applied to daily clinical practice and serve as an important tool for the screening, surveillance, prediction of outcomes, and selection of effective targeted therapies in bladder carcinoma.
Gene Fusions in Human Cancers: A Review Focused on Diagnostic Biomarkers, Method Selections, and Treatments
403-410
10.1615/CritRevOncog.2017020550
Hao
Ni
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Xiao-Tong
Wang
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Ru
Fang
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China
Xiao-Jun
Zhou
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Qiu
Rao
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
gene fusion
immunohistochemistry
FISH
RT-PCR
Recurrent gene fusions in cancers have been successfully applied in clinical diagnoses and treatments. Specific gene rearrangements or other specific cytogenetic translocations may be helpful in separating cancers from benign lesions. Also, the detection of gene fusions has brought great benefits to distinguish molecular subclassifications
of cancers. Numerous approaches have been used to identify cancer-specific abnormalities, including FISH,
RT-PCR, next-generation sequencing, etc. In addition to diagnostic and genetic values, molecular testing has been
becoming a valuable tool in the therapeutic research. Recent clinical trials involving gene fusions in cancers have
also been developing under a rapid speed. Generally, we review gene fusions in cancers, emphasizing on relevant
diagnostic biomarkers, method selections, and treatments.
Genomic Pathology and Biomarkers in Breast Cancer
411-426
10.1615/CritRevOncog.v22.i5-6.60
Zhang
Zhang
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China, 610041
Ping
Tang
Department of Pathology, Loyola University Medical Center, 2160 South First Ave, Maywood, IL 60153, USA
breast cancer
carcinogenesis
biomarker
molecular classification
next generation sequencing
Breast cancer is a highly heterogeneous disease. There are significant differences in morphology, immunophenotype,
clinical behavior, and treatment response in breast cancer, which pose the greatest challenge for managing breast cancer patients. Great advances in breast cancer have been made at the molecular and genomic levels, which not only help us greatly in better understanding the heterogeneity and the carcinogenesis for breast cancer, but also help us in identifying new prognostic markers and therapeutic targets. In this review, we discuss these new findings in detail: (1) the two main pathways of the pathogenesis for breast cancer; (2) the traditional biomarkers including ER, PR, HER2, and some controversial biomarkers - Ki67, p53, AR, FRA for breast cancer; (3) the molecular classification of breast cancer, its IHC surrogates and its application in clinical management; (4) the multigene tests and their applications for breast cancer management; (5) next-generation sequencing and its clinical application for breast cancer; and (6) TIL and PD1/PD-L1 and their application in breast cancer.
Biomarkers of DNA Repair and Related Pathways: Significance of Treatment in Triple-Negative Breast Cancer
427-437
10.1615/CritRevOncog.2017020575
Wenwen
Guo
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Rd, Nanjing
210011, China
Li
Lin
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Rd, Nanjing 010011, China; Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA
Xue
He
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Rd, Nanjing
210011, China
Fengxia
He
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Rd, Nanjing
210011, China
Congyang
Wang
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Rd, Nanjing
210011, China
Nannan
Chen
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Rd, Nanjing
210011, China
Yan
Wang
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Rd, Nanjing
210011, China
triple-negative breast cancer
basal-like breast cancer
homologous recombination repair deficiency
platinum
PARP inhibitor
Triple-negative breast cancer (TNBC) is a complex heterogeneous disease that lacks the expressions of
hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2). Although TNBC make up less than
20% of breast cancer, it accounts for a large number of metastatic cases and deaths. Currently, extensive efforts have been made to look for potentially biomolecular targets for TNBC treatment. Based on the differences of molecular
events identified by gene profiling analysis, the TNBC may be divided into some broad categories: basal-like (BL),
mesenchymal-like (ML), immune-associated, HER2-enriched and luminal/apocrine breast cancers. Most of these are in the BL-TNBC category. BL-TNBC carries a representative molecular event of DNA-repair deficiency that increases the effectiveness of DNA destabilizers (represented by platinum agents) and DNA-damage response inhibitors (represented by PARP inhibitors). However, the results from clinical and preclinical studies have been inconsistent. Herein, we simply outline the progress of breast cancer classification and the significance of DNA repair deficiency in the clinic treatment for TNBCs. Previous studies have shown that the neoadjuvant therapies with platinum agents are effective for early-stage and metastatic TNBC patients with DNA repair defects. The results indicate that proper biomarkers (such as homologous recombination repair defects, HRD) are necessary for predicting the response to chemotherapy and often sufficient to select patients in early-phase treatment. Furthermore, the combination of chemotherapy
drugs and inhibitors of DNA damage response represents a potential therapeutic strategy for TNBCs.
Epigenetic Modifications and Modulators in Prostate Cancer
439-450
10.1615/CritRevOncog.2017020964
Alessia
Cimadamore
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals,
Ancona, Italy
Silvia
Gasparrini
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals,
Ancona, Italy
Marina
Scarpelli
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals,
Ancona, Italy
Andrea
Doria
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals,
Ancona, Italy
Roberta
Mazzucchelli
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals,
Ancona, Italy
Francesco
Massari
Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
Liang
Cheng
Departments of Pathology, Indiana University School of Medicine, Indianapolis, USA;
Department of Urology, Indiana University School of Medicine, Indianapolis, USA; Molecular PathologyDepartment of Pathology and Laboratory MedicineWarren Alpert
Medical School of Brown University | LifespanAcademic Medical CenterAssociate
Director for Shared ResourcesLegorreta CancerCenter at Brown University
Antonio
Lopez-Beltran
Department of Pathology and Surgery, Faculty of Medicine, Cordoba, Spain and Champalimaud Clinical Center, Lisbon, Portugal
Rodolfo
Montironi
Institute of Pathological Anatomy and
Histopathology Polytechnic University of the Marche Region (Ancona) and United Hospitals
Ancona, Italy
DNA methylation
epigenetic modifications
histone methylation
microRNA
target therapy
prostate cancer
Prostate cancer (PCa) is one of the most common malignancies in men. Its clinical behavior ranges from indolent to aggressive. The clinical and morphological methods and features currently adopted show a low predictive value concerning the definition of its level of aggressiveness. Investigations have been led to understand its complex genomic landscape to improve diagnosis and prognosis as well as to define the potential role of new therapeutic targets. Epigenetic changes, including modifications in DNA methylation and histone acetylation, can contribute to the clinical behavior of PCa. MicroRNAs (miRNAs) can be used as potential biomarkers in the definition of PCa. The reversibility of epigenetic modifications opens the door to a potential perspective in the development of epigenetics modulators. The scope of this contribution is to review the main epigenetic modifications identified in PCa, including research on epigenetic modifiers and modulators.
Precision in Diagnostic Molecular Pathology based on Immunohistochemistry
451-469
10.1615/CritRevOncog.2017020548
Ru
Fang
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China
Xiao-Tong
Wang
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Qiu-Yuan
Xia
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China
Xiao-Jun
Zhou
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Qiu
Rao
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
immunohistochemistry
tumor
chromosome translocation
gene amplification
gene mutation
Immunohistochemistry (IHC) is an indispensable tool for molecular pathological diagnosis. It has been applied in the differential diagnosis of benign and malignant tumors, the determination of tumor origin, cell differentiation, and the detection of microorganisms. By enabling the detection of proteins, IHC offers a platform for the assessment of genetic information from tumor genes and molecular pathological changes. Compared with other molecular pathology detection tools, IHC is cheaper, less time-consuming, and less labor-intensive and can be applied
in routine pathological diagnosis efficiently. This review summarizes the IHC biomarkers that can be used to reflect
molecular pathology or even to replace molecular pathology, and it highlights the shortcomings and precautions to be
observed during their applications.
The Roles of Chromatin Remodeling Genes in Pancreatic-Biliary Malignancies
471-479
10.1615/CritRevOncog.2017020587
Claudio
Luchini
Department of Diagnostics and Public Health, University and Hospital Trust of Verona, 37142 Verona, Italy; ARC-Net Research Center, University and Hospital Trust of Verona, 37142 Verona, Italy
Alessia
Nottegar
Department of Surgery, San Bortolo
Hospital, 36100 Vicenza, Italy
ARID1A
BAP1
PBRM1
SWI/SNF
chromatin
pancreas
cholangiocarcinoma
oncogenesis
Recent studies have definitively established that chromatin remodeling is a crucial epigenetic mechanism
not only in physiological conditions but also in influencing cancer biology. It is a dynamic process in which the
chromatin, the functional entity of DNA, can undergo specific modifications by obtaining transcriptional activation or transcriptional silencing. One of the most important recent discoveries in cancer genetics and genomics is that the genes involved in the establishment of chromatin structure, the so called chromatin remodelers, are frequently mutated in different types of human cancer. This review aims to summarize the main novelties related to this topic, describing also the contribution of such genes during oncogenesis. Particularly, we focus on the switch/sucrose non-fermentable complexes and on three of the most important chromatin remodeling genes in biliary and pancreatic
cancer: ARID1A, PBRM1, and BAP1.
Xp11 Translocation Renal Cell Carcinoma and the Mesenchymal Counterparts: An Evolving Concept with Novel Insights on Clinicopathologic Features, Prognosis, Treatment, and Classification
481-497
10.1615/CritRevOncog.2017020558
Xiao-Tong
Wang
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Qiu-Yuan
Xia
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China
Xiao-Jun
Zhou
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
Qiu
Rao
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
renal cell carcinoma
TFE3
alveolar soft-part sarcoma
Xp11 neoplasm with melanocytic
differentiation
perivascular epithelioid cell tumor
The TFE3 gene is one of four members of the micropathalima-associated transcription factor family, along with TFEB, TFEC, and MiTF, located on chromosome Xp11.2. The site is notable for its involvement in translocation in Xp11 translocation renal cell carcinoma (RCC) and the mesenchymal counterparts, including Xp11 neoplasm with melanocytic differentiation/TFE3 rearrangement-associated perivascular epithelioid cell tumor (PEComa)/ melanotic Xp11 translocation renal cancer/melanotic Xp11 neoplasm, and alveolar soft-part sarcoma. By morphologic, immunohistochemical, genetic, and prognostic similarities, alveolar soft-part sarcoma with the ASPSCR1-TFE3 gene fusion has a closer relationship with Xp11 neoplasm with melanocytic differentiation/TFE3 rearrangement-associated PEComa/melanotic Xp11 translocation renal cancer/melanotic Xp11 neoplasm. These Xp11 translocation mesenchymal neoplasms may represent a distinct entity, which overlaps with Xp11 translocation RCC and broadens the
spectrum of Xp11 translocation-associated neoplasms. The impact of individual fusion variants on specific clinicopathologic features of Xp11 translocation RCC has only recently been described. This review provides insight into the clinicopathologic features, prognosis, treatment, and classification of Xp11 translocation RCC and its mesenchymal counterparts, emphasizing the impact of individual fusion variants on specific clinicopathologic features of Xp11 translocation RCC and the relationships among these Xp11 translocation-associated neoplasms.
Eph Receptors: Actors in Tumor Microenvironment
499-505
10.1615/CritRevOncog.2017020557
Xiaodie
Zhou
Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China
Pin
Tu
Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China
Xiao
Chen
Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China
Shuwei
Guo
Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China
Jiandong
Wang
Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China
Eph
receptor tyrosine kinase
tumor microenvironment
Eph/ephrin signaling plays important roles both in embryonic development and human disease. The Eph receptors are involved in tumor development, progression, metastasis, and prognosis. The tumor microenvironment plays a critical role in tumor initiation, progression, metastasis, and resistance to therapy. Increasing data show that Ephs and ephrins mediate cell-cell interactions both in tumor cells and in tumor microenvironment. This review focuses on recent advances in dissecting the role of Eph and ephrin in tumor cells, tumor angiogenesis, epithelial-mesenchymal
transition, hypoxia, and inflammation.
Precise Diagnosis and Treatment of Thymic Epithelial Tumors Based on Molecular Biomarkers
507-514
10.1615/CritRevOncog.2017020577
Jun
Du
Department of Pathology, Jinling Hospital, 305 ZhongShan East Road, 210002 Nanjing Jiangsu, China; Department of Pathology, South District of Anhui Provicinal Hospital, Hefei, 230036, China
Xiao-Jun
Zhou
Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China; Department of Pathology, Jinling Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China
TETs
molecular biomarkers
ERBB
C-KIT
IGF1R
chemotherapy
Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare malignant tumors. The mainstay of treatment patients with TET is surgical resection, and chemotherapy is necessary for patients with tumor invasion or metastasis who are unable to undergo complete radical excision. However, for those patients who are resistant to chemotherapy, targeted therapy has become the most popular tumor treatment program, as well as for thymic tumors. Many genes implicated in tumorigenesis and metastasis have also been reported to be therapeutic targets in thymic malignancies. A significant advance in TET treatment may derive from the identification of novel molecular biomarkers that can improve the diagnosis, prognosis, and treatment of tumors. We review a number of case reports and small clinical trials reporting that a few inhibitors, such as sorafenib and sunitinib, are effective in the treatment of thymoma. In this review, we describe the current potential drug targets and their roles in the development of thymic malignancy.
Genomic Pathology and Cancer Biomarkers: Prostate Cancer
515-525
10.1615/CritRevOncog.2017020539
Kenneth A.
Iczkowski
Department of Pathology, Medical College of Wisconsin, 9200 W. Wisconsin Ave., Milwaukee, WI 53226
prostate cancer
biomarkers
genomics
PTEN
CDKN1B
p27
ERG
Our understanding of genomic pathology and biomarkers for prostate cancer is continually growing. Some promising and useful tissue markers are GSTP1, HOXD3, cell cycle proteins, chromatin remodeling proteins, androgen receptor, Stat5a/b, ERG, and PTEN. Serum and urine markers are mostly either prostate-specific antigen or newer tests using one or more other kallikreins or sarcosine. The data and evidence for all of these markers and the commercial tests using them are reviewed here.
Oncogenic Signaling Pathways and Pathway-Based Therapeutic Biomarkers in Lymphoid Malignancies
527-557
10.1615/CritRevOncog.2017020816
Ruifang
Sun
Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi, China; Tumor Biobank, Shanxi Cancer Hospital, Taiyuan, Shanxi, China
Jinfen
Wang
Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi, China
Ken H.
Young
Division of Hematopathology
Department of Pathology
Duke University School of Medicine
biomarker
lymphoma
oncogenesis
signaling pathway
therapeutic target
Lymphoma is characterized by heterogeneous biology, pathologic features, and clinical outcome. This has been proven by accumulating pathologic and molecular evidence attributed to underlying aberrant alterations at genetic, epigenetic, transcriptional, protein, microenvironmental levels, and dysregulated oncogenic signaling pathways. In the era of precision medicine, targeting oncogenic pathways to design drugs and to optimize treatment regimens for the lymphoma patients is feasible and clinically significant. As such, further understanding of the biology and the mechanisms behind lymphoma development and identification of oncogenic pathway activation and pathway-based biomarkers to better design precise therapies are challenging but hopeful. Furthermore, pathway-based targeted therapies in combination with traditional chemotherapy, single specific targeted antibody therapy, and immunotherapy might raise the hope for the patients with lymphoma, especially for relapsed and refractory lymphoma patients.
Next-Generation Sequencing for Minimal Residual Disease Surveillance in Acute Lymphoblastic Leukemia: An Update
559-567
10.1615/CritRevOncog.2017020588
Cynthia
Reyes-Barron
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
W. Richard
Burack
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
Paul G.
Rothberg
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
Yi
Ding
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642
minimal residual disease
next generation sequencing
acute lymphoblastic leukemia
Monitoring minimal residual disease (MRD) is an important predictor of outcome in acute lymphoblastic leukemia (ALL) and is used in risk stratification, prognosis determination, and therapy guidance. Several laboratory techniques have proven utility for characterizing leukemic cells and following MRD through diagnosis, remission and possible recurrence. Methods for determining MRD are based on the detection of leukemia-specific aberrant immunophenotypes by mulitparameter flow cytometry or the evaluation of leukemia-specific rearranged immunoglobulin or T-cell receptor sequences by quantitative real-time PCR. Next-generation sequencing (NGS) is emerging as a new flexible and sensitive tool to detect MRD, which allows identification of clonal composition and scalable sensitivity depending on sequence coverage. As NGS becomes more accessible and affordable, guidelines should be established for its application to MRD surveillance.
Index, Volume 22, 2017
569-574
10.1615/CritRevOncog.v22.i5-6.170