scholarly journals Systems medicine dissection of chromosome 1q amplification reveals oncogenic regulatory circuits and informs targeted therapy in cancer

2021 ◽  
Author(s):  
Nikolaos Trasanidis ◽  
Alexia Katsarou ◽  
Kanagaraju Ponnusamy ◽  
Yao-An Shen ◽  
Ioannis V Kostopoulos ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Gene Signature ◽  
Clinical Impact ◽  
Systems Medicine ◽  
Chromosome 1Q ◽  
Regulatory Circuits ◽  
Oncogenic Pathways ◽  
Cancer Multiple ◽  
Therapy Strategies ◽  
Genetic Amplification

Understanding the biological and clinical impact of copy number aberrations (CNA) in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring adverse prognosis in several cancers, including the blood cancer, multiple myeloma (MM). Although several chr1q genes portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here we integrate patient multi-omics datasets with genetic variables to identify 103 adverse prognosis genes in chr1q-amp MM. Amongst these, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed super-enhancers, PBX1 directly regulates critical oncogenic pathways, whilst in co-operation with FOXM1, activates a proliferative gene signature which predicts adverse prognosis across multiple cancers. Notably, pharmacological disruption of the PBX1-FOXM1 axis, including with a novel PBX1 inhibitor is selectively toxic against chr1q-amp cancer cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes and proposes novel CNA-targeted therapy strategies in cancer.

scholarly journals Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma

Blood ◽  
2022 ◽  
Author(s):  
Nikolaos Trasanidis ◽  
Alexia Katsarou ◽  
Kanagaraju Ponnusamy ◽  
Yao-An Shen ◽  
Ioannis V Kostopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Targeted Therapy ◽  
Gene Signature ◽  
Systems Medicine ◽  
Chromosome 1Q ◽  
Oncogenic Pathways ◽  
Molecule Inhibitor ◽  
Cancer Multiple ◽  
Therapy Strategies ◽  
Genetic Amplification

Understanding the biological and clinical impact of copy number aberrations (CNA) for the development of precision therapies in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring adverse prognosis in several types of cancer, including in the blood cancer multiple myeloma (MM). Although several genes across chr1q portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here, with reference to the 3D chromatin structure, we integrate MM patient multi-omics datasets with genetic variables to obtain an associated clinical risk map across chr1q and to identify 103 adverse prognosis genes in chr1q-amp MM. Prominent amongst these genes, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed super-enhancers, PBX1 directly regulates critical oncogenic pathways and a FOXM1-dependent transcriptional programme. Together, PBX1 and FOXM1 activate a proliferative gene signature which predicts adverse prognosis across multiple types of cancer. Notably, pharmacological disruption of the PBX1-FOXM1 axis with existing agents (thiostrepton) and a novel PBX1 small-molecule inhibitor (T417) is selectively toxic against chr1q-amplified myeloma and solid tumour cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes and proposes novel CNA-targeted therapy strategies in multiple myeloma and other types of cancer.

DEVELOPMENT OF COMPOSITION AND PRODUCTION TECHNOLOGIES PAZOPANIB TABLET 400 MG

2021 ◽  
pp. 83-87
Author(s):  
А.Е. ЖУМАКАНОВА ◽  
А.Р. ИБРАГИМОВА ◽  
Г.О. УСТЕНОВА
Keyword(s):  
Targeted Therapy ◽  
Cancer Cells ◽  
Soft Tissue Sarcomas ◽  
Targeted Drugs ◽  
Cancer Treatments ◽  
Production Technologies ◽  
Cancer Multiple ◽  
Or Genes ◽  
Cancer Targeted Therapy ◽  
Better Than

Таргетные методы лечения рака - это лекарства, нацеленные на определенные части раковых клеток, такие как белки или гены, которые способствуют росту и распространению раковых клеток. Трагетная терапия при определенных типах раках является эффективной. При некоторых типах рака таргетная терапия может работать лучше, чем другие методы лечения. От английского target - цель, мишень. Природа таргетных лекарств очень специфична и при разработке они направляются под конкретный мутировавший ген раковой клетки определенного вида опухолевого новообразования. В настоящий момент разными странами разработаны эффективные таргетные препараты для лечения различных генетических форм рака молочной железы, множественной миеломы, лимфомы, рака предстательной железы, меланомы, сарком мягких тканей [1]. Targeted cancer treatments are medicaments that target specific parts of cancer cells, such as proteins or genes that growing power and spread of cancer cells. Targeted therapy for certain types of cancers is effective. For some types of cancer, targeted therapy may work better than other treatments. The nature of targeted drugs is very specific and when developed, they are directed to a specific mutated gene of a cancer cell of a certain type of tumor. Currently, different countries have developed effective targeted drugs for the treatment of various genetic forms of breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma, soft tissue sarcomas.

Targeting aggressive B-cell lymphomas with cell-penetrating peptides

2007 ◽  
Vol 35 (4) ◽  
pp. 802-806 ◽  
Author(s):  
A. Melnick
Keyword(s):  
Targeted Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
Functional Characterization ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Cell Penetrating Peptides ◽  
Current Therapy ◽  
Molecular Heterogeneity ◽  
Oncogenic Pathways

DLBCL (diffuse large B-cell lymphoma) is the most common subtype of non-Hodgkin's lymphoma. Current therapy for patients includes chemotherapy and monoclonal antibodies. Although oncogene-targeted therapy is dramatically successful for patients with certain kinds of leukaemias, there are no such agents yet for DLBCL. One reason for this is that several key oncogenes involved in DLBCL pathogenesis are transcription factors, which are difficult to therapeutically target with small molecules. Recent advances in the structural and functional characterization of DLBCL oncogenes have facilitated design of CPPs (cellpenetrating peptides) with potent inhibitory effects on DLBCL and other aggressive lymphomas. CPPs targeting the Bcl (B-cell lymphoma)-6, Bcl-2, Myc and NF-κB (nuclear factor κB) oncogenic pathways, among others, could improve efficacy and reduce toxicity of anti-lymphoma therapy. Another barrier towards effective therapy in DLBCL is its profound molecular heterogeneity. Combinatorial administration of oncogene-targeted CPPs based on the molecular profiles of individual patient tumours could allow individualized targeted therapy regimens to be developed.

scholarly journals Multiple Chemotherapy-Based Combination Therapy Strategies for Advanced Lung Cancer Patients: A Systematic Review and Network Meta-Analysis

2020 ◽  
Author(s):  
Lecai Xiong ◽  
Yuquan Bai ◽  
Xuefeng Zhou ◽  
Ming Xu ◽  
Gaofeng Pan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Combination Therapy ◽  
Meta Analysis ◽  
Objective Response ◽  
Advanced Lung Cancer ◽  
Combination Therapies ◽  
Outcome Indicators ◽  
Therapeutic Benefits ◽  
Therapy Strategies

Background: At present, the treatments for patients with advanced lung cancer focus on chemotherapy, targeted therapy, immunotherapy, or a combination of multiple treatments. Purpose: The main purpose of this study is to compare the various chemotherapy-based combination therapies and find the best one for patients with advanced lung cancer. Methods: Based on database (PubMed, EMBASE and Medline) for randomized controlled trials of advanced lung cancer with combination therapy from 2008 to 2020, we searched literatures with overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse as outcome indicators and established a Bayesian mesh meta-analysis for multiple treatment strategies. Then, we combined the results of four outcome indicators to find out the best chemotherapy-based combination therapy strategy for patients with advanced lung cancer, further, we tried to screen out the best drugs of which were commonly used now. Results: It contained a total of 51 studies, including five combination therapies: Chemotherapy/Chemotherapy plus placebo (CT), chemotherapy plus one targeted therapy drug (CT+T), chemotherapy plus two targeted therapy drugs (CT+T+T), chemotherapy combined with immunotherapy (CT+I) or chemotherapy combined with biotherapy (CT+B). In terms of four outcome indicators, CT+I showed the best therapeutic benefits. In the comparison of immunotherapy drugs, pembrolizumab showed the best effect. Conclusion: Our results showed that, among the multiple chemotherapy-based combination therapy strategies, chemotherapy combined with immunotherapy is the best choice for patients with advanced lung cancer, and pembrolizumab combined with chemotherapy has the best effect.

scholarly journals Deep learning in systems medicine

2020 ◽  
Author(s):  
Haiying Wang ◽  
Estelle Pujos-Guillot ◽  
Blandine Comte ◽  
Joao Luis de Miranda ◽  
Vojtech Spiwok ◽  
...  
Keyword(s):  
Deep Learning ◽  
Precision Medicine ◽  
Human Body ◽  
Review Paper ◽  
Heterogeneous Data ◽  
Clinical Impact ◽  
High Dimensional ◽  
Great Promise ◽  
Systems Medicine ◽  
Prevention And Treatment

Abstract Systems medicine (SM) has emerged as a powerful tool for studying the human body at the systems level with the aim of improving our understanding, prevention and treatment of complex diseases. Being able to automatically extract relevant features needed for a given task from high-dimensional, heterogeneous data, deep learning (DL) holds great promise in this endeavour. This review paper addresses the main developments of DL algorithms and a set of general topics where DL is decisive, namely, within the SM landscape. It discusses how DL can be applied to SM with an emphasis on the applications to predictive, preventive and precision medicine. Several key challenges have been highlighted including delivering clinical impact and improving interpretability. We used some prototypical examples to highlight the relevance and significance of the adoption of DL in SM, one of them is involving the creation of a model for personalized Parkinson’s disease. The review offers valuable insights and informs the research in DL and SM.

scholarly journals Mucosal Melanoma: Pathological Evolution, Pathway Dependency and Targeted Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanni Ma ◽  
Ronghui Xia ◽  
Xuhui Ma ◽  
Robert L. Judson-Torres ◽  
Hanlin Zeng
Keyword(s):  
Targeted Therapy ◽  
Mapk Pathway ◽  
Treatment Options ◽  
Mucosal Melanoma ◽  
Telomere Maintenance ◽  
Evolutionary Trajectories ◽  
Detection And Diagnosis ◽  
New Biomarkers ◽  
Rna Maturation ◽  
Therapy Strategies

Mucosal melanoma (MM) is a rare melanoma subtype that originates from melanocytes within sun-protected mucous membranes. Compared with cutaneous melanoma (CM), MM has worse prognosis and lacks effective treatment options. Moreover, the endogenous or exogenous risk factors that influence mucosal melanocyte transformation, as well as the identity of MM precursor lesions, are ambiguous. Consequently, there remains a lack of molecular markers that can be used for early diagnosis, and therefore better management, of MM. In this review, we first summarize the main functions of mucosal melanocytes. Then, using oral mucosal melanoma (OMM) as a model, we discuss the distinct pathologic stages from benign mucosal melanocytes to metastatic MM, mapping the possible evolutionary trajectories that correspond to MM initiation and progression. We highlight key areas of ambiguity during the genetic evolution of MM from its benign lesions, and the resolution of which could aid in the discovery of new biomarkers for MM detection and diagnosis. We outline the key pathways that are altered in MM, including the MAPK pathway, the PI3K/AKT pathway, cell cycle regulation, telomere maintenance, and the RNA maturation process, and discuss targeted therapy strategies for MM currently in use or under investigation.

Inflammatory breast cancer remains the most aggressive form of breast cancer. A multimodality therapeutic plan has shown improved survival results

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Locally Advanced ◽  
Tumor Formation ◽  
Novel Therapy ◽  
Acquired Drug Resistance ◽  
Future Studies ◽  
Aggressive Form ◽  
Oncogenic Pathways ◽  
Therapy Strategies

Even though inflammatory breast cancer remains the most aggressive form of breast cancer, with the highest rates of morbidity and mortality, other types of breast cancer do exist. In addition to Nneoadjuvant chemotherapy, surgery, and radiation, a multimodality therapeutic plan including these procedures has shown improved survival results for locally advanced disease. Most current research focuses on finding new and novel therapy strategies that can allow people with inflammatory breast cancer to have a longer lifespan. The availability of genomic testing enables early detection of primary and acquired drug resistance as well as the assessment of treatment choices. In addition, an in-depth understanding of inflammatory breast cancer molecular biology will assist in the discovery of critical genomic alterations and oncogenic pathways that contribute to tumor formation and spreading. Future studies will give more valuable information that may be used in clinics to better treatment outcomes.

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