scholarly journals How to use new biology to guide therapy in multiple myeloma

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 342-349 ◽  
Author(s):  
Gareth J. Morgan ◽  
Martin F. Kaiser
Keyword(s):  
Multiple Myeloma ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Survival Rates ◽  
Current Treatment ◽  
Next Generation ◽  
Molecular Subgroups ◽  
Treatment Protocols ◽  
Sequencing Technologies ◽  
A Genome

Abstract Recent advances in multiple myeloma (MM) therapy have led to significantly longer median survival rates and some patients being cured. At the same time, our understanding of MM biology and the molecular mechanisms driving the disease is constantly improving. Next-generation sequencing technologies now allow insights into the genetic aberrations in MM at a genome-wide scale and across different developmental stages in the course of an individual tumor. This improved knowledge about MM biology needs to be rapidly translated and transformed into diagnostic and therapeutic applications to finally achieve cure in a larger proportion of patients. As a part of these translational efforts, novel drugs that inhibit oncogenic proteins overexpressed in defined molecular subgroups of the disease, such as FGFR3 and MMSET in t(4;14) MM, are currently being developed. The potential of targeted next-generation diagnostic tests to rapidly identify clinically relevant molecular subgroups is being evaluated. The technical tools to detect and define tumor subclones may potentially become clinically relevant because intraclonal tumor heterogeneity has become apparent in many cancers. The emergence of different MM subclones under the selective pressure of treatment is important in MM, especially in the context of maintenance therapy and treatment for asymptomatic stages of the disease. Finally, novel diagnostic and therapeutic achievements have to be implemented into innovative clinical trial strategies with smaller trials for molecularly defined high-risk patients and large trials with a long follow-up for the patients most profiting from the current treatment protocols. These combined approaches will hopefully transform the current one-for-all care into a more tailored, individual therapeutic strategy for MM patients.

scholarly journals Genomics of medulloblastoma: from Giemsa-banding to next-generation sequencing in 20 years

2010 ◽  
Vol 28 (1) ◽  
pp. E6 ◽  
Author(s):  
Paul A. Northcott ◽  
James T. Rutka ◽  
Michael D. Taylor
Keyword(s):  
Next Generation Sequencing ◽  
Molecular Mechanisms ◽  
Genomic Medicine ◽  
Prognostic Significance ◽  
Next Generation ◽  
Sequencing Technologies ◽  
Disease Stratification ◽  
Insight Into ◽  
Generation Sequencing

Advances in the field of genomics have recently enabled the unprecedented characterization of the cancer genome, providing novel insight into the molecular mechanisms underlying malignancies in humans. The application of high-resolution microarray platforms to the study of medulloblastoma has revealed new oncogenes and tumor suppressors and has implicated changes in DNA copy number, gene expression, and methylation state in its etiology. Additionally, the integration of medulloblastoma genomics with patient clinical data has confirmed molecular markers of prognostic significance and highlighted the potential utility of molecular disease stratification. The advent of next-generation sequencing technologies promises to greatly transform our understanding of medulloblastoma pathogenesis in the next few years, permitting comprehensive analyses of all aspects of the genome and increasing the likelihood that genomic medicine will become part of the routine diagnosis and treatment of medulloblastoma.

scholarly journals Targeting NF-κB Signaling for Multiple Myeloma

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2203 ◽  
Author(s):  
Ada Hang-Heng Wong ◽  
Eun Myoung Shin ◽  
Vinay Tergaonkar ◽  
Wee-Joo Chng
Keyword(s):  
Multiple Myeloma ◽  
Molecular Mechanisms ◽  
Nuclear Factor Kappa B ◽  
Hematologic Malignancy ◽  
Survival Rates ◽  
Nuclear Factor ◽  
The Past ◽  
The World ◽  
Future Drug ◽  
Research Findings

Multiple myeloma (MM) is the second most common hematologic malignancy in the world. Even though survival rates have significantly risen over the past years, MM remains incurable, and is also far from reaching the point of being managed as a chronic disease. This paper reviews the evolution of MM therapies, focusing on anti-MM drugs that target the molecular mechanisms of nuclear factor kappa B (NF-κB) signaling. We also provide our perspectives on contemporary research findings and insights for future drug development.

scholarly journals Micropapillary Carcinoma of the Bladder: Recent Advances

2019 ◽  
pp. 1-10
Author(s):  
Jim Hsu ◽  
Jae Y. Ro
Keyword(s):  
Urothelial Carcinoma ◽  
Molecular Mechanisms ◽  
Current Treatment ◽  
Invasive Micropapillary Carcinoma ◽  
Micropapillary Carcinoma ◽  
Treatment Protocols ◽  
Immunohistochemical Markers ◽  
Recent Advances ◽  
Carcinoma Of The Bladder

The 2016 WHO classification of tumors of the urothelial tract recently revised the classification of invasive urothelial carcinoma to include nested, microcystic, micropapillary, plasmacytoid, sarcomatoid, giant cell, and poorly differentiated variants, among others. In particular, invasive micropapillary carcinoma (IMPC) is now recognized as a distinct entity with aggressive features, including higher-stage disease, invasive features, and poorer response to intravesical chemotherapy. In this review, we highlight recent studies that further characterize the histopathology, immunohistochemistry, molecular mechanisms, and clinical implications of a diagnosis of IMPC. Because the correct morphologic diagnosis of IMPC is critical in terms of clinical management, we explore the diagnostic criteria of IMPC and differential diagnosis of urothelial IMPC from non-urothelial sites, highlighting studies that examine both traditional urothelial immunohistochemical markers as well as novel markers. We highlight recent advances in the molecular sub-categorization of IMPC, and review the differences compared to other forms of urothelial carcinoma. Optimal management of patients with IMPC is still unclear, although early cystectomy, regardless of pathologic stages, is recommended. We also highlight several studies that address the clinical challenges as well as current treatment protocols for IMPC.

A comparison between next-generation sequencing and ASO-qPCR for minimal residual disease detection in multiple myeloma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8601-8601
Author(s):  
Hiroyuki Takamatsu ◽  
Ryoichi Murata ◽  
Jianbiao Zheng ◽  
Martin Moorhead ◽  
Yasushi Terasaki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Next Generation Sequencing ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Survival Rates ◽  
Japanese Patients ◽  
Next Generation ◽  
Universal Primer ◽  
Generation Sequencing ◽  
Minimal Residual

8601 Background: Although molecular CR in multiple myeloma (MM) can be assessed by allele-specific oligonucleotide (ASO)-PCR, this technique requires preparation of clonotype-specific primers for each individual which is laborious and time-consuming. The usage of the LymphoSIGHT method, a next-generation sequencing (NGS)-based platform, may overcome these challenges and increase sensitivity and specificity. We compared the LymphoSIGHT approach with ASO-qPCR for minimal residual disease (MRD) detection in autografts in the autologous peripheral blood stem cell transplantation (ASCT) setting. Methods: Seventeen Japanese patients with newly diagnosed MM who received various induction regimens prior to ASCT were retrospectively analyzed. All patients had achieved a PR or CR after ASCT. Bone marrow (BM) slides from 13 MM patients and fresh BM cells from 4 MM patients at diagnosis as well as autografts were obtained for DNA extraction. Using universal primer sets, we amplified IGH variable (V), diversity (D), and joining (J) gene segments, IGH-DJ, and IGK from genomic DNA. Amplified products were subjected to deep sequencing using NGS. Reads were analyzed using standardized algorithms for clonotype determination. Myeloma-specific clonotypes were identified for each patient based on their high frequency in BM samples. The presence of the myeloma clonotype was then assessed in follow-up samples. Results: MRD in autografts was detected in 6 of 17 (35%) by ASO-qPCR and 13 of 17 (76%) by NGS. When MRD was assessed by NGS, 6 MRD (+) cases received post-ASCT therapy while 4 MRD (-) cases and 7 MRD (+) cases were followed without post-ASCT therapy. The MRD (-) cases tended to show a better PFS than the MRD (+) cases with post-ASCT therapy (P = 0.26) and those without post-ASCT therapy (P = 0.09) although overall survival rates were comparable among the three groups. There was no difference in PFS between MRD (-) and MRD (+) cases when MRD was assessed by ASO-qPCR (P = 0.6). These studies will be extended in 30 additional MM patients, and results will be presented. Conclusions: MRD-negativity in autografts revealed by NGS may be more closely associated with durable remission of MM than that revealed by ASO-qPCR.

scholarly journals Molecular Profiling and Minimal Residual Disease Monitoring in Multiple Myeloma Patients: A Literature Review

2021 ◽  
Vol 14 (4) ◽  
pp. 436-443
Author(s):  
Aleksandra Vladimirovna Semyanikhina ◽  
E.E. Tolstykh
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Molecular Genetic ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Malignant Neoplasm ◽  
Current Treatment ◽  
Genetic Profile ◽  
Minimal Residual

A personalized approach is a promising tool for malignant neoplasm (MN) treatment. Gaining success and benefit assessment of this approach were considerably facilitated by the implementation of omix techniques which allow to obtain comprehensive information on the tumor genome and transcriptome state with identifying potential biomarkers and targets for directed drug action. Despite the exponential growth in the number of sequenced tumor genomes, some of them are not subject of active clinical studies, although obviously and increasingly require optimization of current treatment regimens. One of these pathologies is multiple myeloma (MM). Considerable advances in its diagnosis and treatment have substantially increased survival rates. However, MM cannot be removed from the list of fatal diseases, yet. It is a neoplasm which needs to be further studied and explored for implementation of new treatment strategies, most of which would be based on pheno- and genotypic characteristics of tumor cells. The present review deals with the state of the art in the study of the MM molecular genetic profile, minimal residual disease (MRD) monitoring as well as potentials of the new generation sequencing for MRD diagnosis, prognosis, estimation, and search for predictors aimed at chemotherapy optimization.

scholarly journals Dissection of gene regulatory networks in embryonic stem cells by means of high-throughput sequencing

2009 ◽  
Vol 390 (11) ◽  
Author(s):  
Christian Beisel ◽  
Renato Paro
Keyword(s):  
Gene Expression ◽  
Next Generation Sequencing ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem ◽  
Next Generation ◽  
Cell Fate Decisions ◽  
A Genome ◽  
Generation Sequencing

Abstract Transcription factor regulation of gene expression and chromatin-controlled epigenetic memory systems are closely cooperating in establishing the pluripotent state of embryonic stem (ES) cells and maintaining cell fate decisions throughout development of an organism. A thorough understanding of the regulatory transcriptional circuitry that rules the underlying plastic yet heritable gene expression programs in ES cells is of great importance. With the advent of next-generation sequencing technologies facilitating the quantitative assessment of functional genomics assays it is now feasible to interrogate transcription networks at a genome-wide scale. Here, we discuss the application of next-generation sequencing in elucidating the molecular mechanisms underlying ES cell function.

Impact of Natural Dietary Agents on Multiple Myeloma Prevention and Treatment: Molecular Insights and Potential for Clinical Translation

2020 ◽  
Vol 27 (2) ◽  
pp. 187-215 ◽  
Author(s):  
Lavinia Raimondi ◽  
Angela De Luca ◽  
Gianluca Giavaresi ◽  
Agnese Barone ◽  
Pierosandro Tagliaferri ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Multiple Myeloma ◽  
Natural Products ◽  
Bone Disease ◽  
Molecular Mechanisms ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
Signal Transduction Pathways ◽  
Pharmacologically Active ◽  
Dietary Agents

: Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed to shed light on the effects of natural products on tumor growth and survival, disclosing the most relevant signal transduction pathways targeted by such compounds. Overall, anti-inflammatory, anti-oxidant and cytotoxic effects of dietary agents on tumor cells are supported either by results from epidemiological or animal studies and even by clinical trials. : Multiple myeloma is a hematologic malignancy characterized by abnormal proliferation of bone marrow plasma cells and subsequent hypercalcemia, renal dysfunction, anemia, or bone disease, which remains incurable despite novel emerging therapeutic strategies. Notably, increasing evidence supports the capability of dietary natural compounds to antagonize multiple myeloma growth in preclinical models of the disease, underscoring their potential as candidate anti-cancer agents. : In this review, we aim at summarizing findings on the anti-tumor activity of dietary natural products, focusing on their molecular mechanisms, which include inhibition of oncogenic signal transduction pathways and/or epigenetic modulating effects, along with their potential clinical applications against multiple myeloma and its related bone disease.

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature

2019 ◽  
Vol 20 (10) ◽  
pp. 1008-1017 ◽  
Author(s):  
Vandita Kakkar ◽  
Manoj Kumar Verma ◽  
Komal Saini ◽  
Indu Pal Kaur
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Treatment Options ◽  
Oral Submucous Fibrosis ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Developed Countries ◽  
Current Treatment ◽  
Poor Overall Survival ◽  
Hereditary Disorders

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

Cancer Proteomics: New Horizons and Insights into Therapeutic Applications

2020 ◽  
Vol 17 ◽  
Author(s):  
Perumal Subramaniana ◽  
Jaime Jacqueline Jayapalan ◽  
Puteri Shafinaz Abdul-Rahmanb
Keyword(s):  
Molecular Mechanisms ◽  
Rapid Development ◽  
New Horizons ◽  
Cancer Management ◽  
Proteomic Approach ◽  
Cancer Proteomics ◽  
Therapeutic Outcomes ◽  
A Genome ◽  
Highly Sensitive ◽  
Dimensional Electrophoresis

A proteome is an efficient rendition of a genome, unswervingly controlling various cancer processes. Molecular mechanisms of several cancer processes have been unraveled by proteomic approach. Thus far, numerous tumors of diverse status have been investigated by two-dimensional electrophoresis. Numerous biomarkers have been recognized and precise categorization of apparent lesions has led to the timely detection of various cancers in persons at peril. Currently used pioneering approaches and technologies in proteomics have led to highly sensitive assays of cancer biomarkers and improved the early diagnosis of various cancers. The discovery of novel and definite biomarker signatures further widened our perceptive of the disease and novel potent drugs for efficient and aimed therapeutic outcomes in persistent cancers have emerged. However, a major limitation, even today, of proteomics is resolving and quantifying the proteins of low abundance. Despite the rapid development of proteomic technologies and their applications in cancer management, annulling the shortcomings of present proteomic technologies and development of better methods are still desirable. The main objectives of this review are to discuss the developing aspects, merits and demerits of pharmacoproteomics, redox proteomics, novel approaches and therapies being used for various types of cancer based on proteome studies.

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