• Title/Summary/Keyword: Targeted therapy

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Medulloblastoma in the Molecular Era

  • Kuzan-Fischer, Claudia Miranda;Juraschka, Kyle;Taylor, Michael D.
    • Journal of Korean Neurosurgical Society
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    • v.61 no.3
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    • pp.292-301
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    • 2018
  • Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.

TRAIL Based Therapy: Overview of Mesenchymal Stem Cell Based Delivery and miRNA Controlled Expression of TRAIL

  • Attar, Rukset;Sajjad, Farhana;Qureshi, Muhammad Zahid;Tahir, Fizza;Hussain, Ejaz;Fayyaz, Sundas;Farooqi, Ammad Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6495-6497
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    • 2014
  • Rapidly increasing number of outstanding developments in the field of TRAIL mediated signaling have revolutionized our current information about inducing and maximizing TRAIL mediated apoptosis in resistant cancer cells. Data obtained with high-throughput technologies have provided finer resolution of tumor biology and now it is known that a complex structure containing malignant cells strictly coupled with a large variety of surrounding cells constitutes the tumor stroma. Utility of mesenchymal stem cells (MSCs) as cellular vehicles has added new layers of information. There is sufficient experimental evidence substantiating efficient gene deliveries into MSCs by retroviral, lentiviral and adenoviral vectors. Moreover, there is a paradigm shift in molecular oncology and recent high impact research has shown controlled expression of TRAIL in cancer cells on insertion of complementary sequences for frequently downregulated miRNAs. In this review we have attempted to provide an overview of utility of TRAIL engineered MSCs for effective killing of tumor and potential of using miRNA response elements as rheostat like switch to control expression of TRAIL in cancer cells.

Novel Approaches for Efficient Antifungal Drug Action

  • Lee, Heejeong;Lee, Dong Gun
    • Journal of Microbiology and Biotechnology
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    • v.28 no.11
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    • pp.1771-1781
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    • 2018
  • The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

Concomitant EGFR Inhibitors Combined with Radiation for Treatment of Non-small Cell Lung Carcinoma

  • Zheng, De-Jie;Yu, Guo-Hua;Gao, Jian-Feng;Gu, Jun-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4485-4494
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    • 2013
  • Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.

Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting

  • Eun, Kiyoung;Ham, Seok Won;Kim, Hyunggee
    • BMB Reports
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    • v.50 no.3
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    • pp.117-125
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    • 2017
  • Most of the cancers are still incurable human diseases. According to recent findings, especially targeting cancer stem cells (CSCs) is the most promising therapeutic strategy. CSCs take charge of a cancer hierarchy, harboring stem cell-like properties involving self-renewal and aberrant differentiation potential. Most of all, the presence of CSCs is closely associated with tumorigenesis and therapeutic resistance. Despite the numerous efforts to target CSCs, current anti-cancer therapies are still impeded by CSC-derived cancer malignancies; increased metastases, tumor recurrence, and even acquired resistance against the anti-CSC therapies developed in experimental models. One of the most forceful underlying reasons is a "cancer heterogeneity" due to "CSC plasticity". A comprehensive understanding of CSC-derived heterogeneity will provide novel insights into the establishment of efficient targeting strategies to eliminate CSCs. Here, we introduce findings on mechanisms of CSC reprogramming and CSC plasticity, which give rise to phenotypically varied CSCs. Also, we suggest concepts to improve CSC-targeted therapy in order to overcome therapeutic resistance caused by CSC plasticity and heterogeneity.

Impressive effect of cisplatin monotherapy on a patient with heavily pretreated triple-negative breast cancer with poor performance

  • Baek, Dong Won;Park, Ji-Young;Lee, Soo Jung;Chae, Yee Soo
    • Journal of Yeungnam Medical Science
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    • v.37 no.3
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    • pp.230-235
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    • 2020
  • Systemic therapy for metastatic triple-negative breast cancer (TNBC) still remains challenging because there are no targeted agents or endocrine therapies currently available. The present case report documents the successful use of cisplatin monotherapy to manage a heavily pretreated TNBC patient showing poor response to therapy. The patient was a 51-year-old woman who had already undergone several lines of systemic chemotherapy for widespread TNBC. Although the mutation analysis performed on DNA isolated from blood cells and progressed lesion samples confirmed the tumor to be germline BRCA wild-type, cisplatin monotherapy was administered based on the increasing evidence of safety and efficacy of platinum for breast cancer. After three cycles of cisplatin treatment, the patient's metastatic lesions dramatically improved without any major toxicity, and she completed 17 cycles with good response. This case study indicates that patients with heavily pretreated TNBC can potentially achieve a good response to cisplatin monotherapy.

Targeted Silencing of Inhibitors of Apoptosis Proteins with siRNAs: A Potential Anti-cancer Strategy for Hepatocellular Carcinoma

  • Li, Gang;Chang, Hong;Zhai, Yun-Peng;Xu, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.4943-4952
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    • 2013
  • Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a very poor prognosis. Despite significant improvements in diagnosis and treatment in recent years, the long-term therapeutic efficacy is poor, partially due to tumor metastasis, tecurrence, and resistance to chemo-or radio-therapy. Recently, it was found that a major feature of tumors is a combination of unrestrained cell proliferation and impaired apoptosis. There are now 8 recogized members of the IAP-family: NAIP, c-IAP1, c-IAP2, XIAP, Survivin, Bruce, Livin and ILP-2. There proteins all contribute to ingibition of apoptosis, and provide new potential avenues of cancer treatment. As a powerful tool to suppress gene expression in mammalian cells, RNAi species for inhibiting IAP genes cab be directed against cancers. This review will provide a brief introduction to recent developments of the application IAP-siRNA in tumor studies, with the aim of inspiring future treatment of HCC.

Case Analysis of the Effects of Nucleoplasty and Chemonucleolysis on the Intervertebral Disc (척추의 추간판에 대한 수핵성형술과 화학적수핵융해술의 영향 증례분석)

  • Hong, Youngki
    • Archives of Orthopedic and Sports Physical Therapy
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    • v.14 no.2
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    • pp.73-80
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    • 2018
  • Purpose: This study was evaluated the effects of nucleoplasty and chemonucleolysis, as interventional treatments for herniated intervertebral disc disease, on spinal tissues. Methods: Nucleoplasty using plasma beam and chemonucleolysis with collagenase were conducted on the spinal motion segments that were dissected from of human cadaver spine under fluoroscopic guidance. After the procedure, the intervertebral discs were transected, and the changes in gross findings were examined. Subsequently, the influence of the procedure on the nucleus pulposus, annuls fibrosus, and endplate was analyzed through a pathologic examination. Results: Nucleoplasty was confirmed to eliminate the local range of tissues in nucleus pulposus according to the procedure tract and to not affect other tissues. In chemonucleolysis, we found that collagenase diffused from the surgical site within the nucleus pulposus and was not present in the annulus fibrosus and endplate. Conclusions: The clinically-used interventional treatments that were investigated here were not found to do not cause additional damage to areas other than those targeted.

Precision Medicine in Head and Neck Cancer (두경부암에서 정밀의료)

  • Hye-sung Park;Jin-Hyoung Kang
    • Korean Journal of Head & Neck Oncology
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    • v.39 no.1
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    • pp.1-9
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    • 2023
  • Technological advancement in human genome analysis and ICT (information & communication technologies) brought 'precision medicine' into our clinical practice. Precision medicine is a novel medical approach that provides personalized treatments tailored to each individual by precisely segmenting patient populations, based on robust data including a person's genetic information, disease information, lifestyle information, etc. Precision medicine has a potential to be applied to treating a range of tumors, in addition to non-small cell lung cancer, in which precision oncology has been actively practiced. In this article, we are reviewing precision medicine in head and neck cancer (HNC) with focus on tumor agnostic biomarkers and treatments such as NTRK, MSI-H/dMMR, TMB-H and BRAF V600E, all of which were recently approved by U.S. Food and Drug Administration (FDA).

Recent Advances in Cell Therapeutics for Systemic Autoimmune Diseases

  • Youngjae Park;Seung-Ki Kwok
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.10.1-10.17
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    • 2022
  • Systemic autoimmune diseases arise from loss of self-tolerance and immune homeostasis between effector and regulator functions. There are many therapeutic modalities for autoimmune diseases ranging from conventional disease-modifying anti-rheumatic drugs and immunosuppressants exerting nonspecific immune suppression to targeted agents including biologic agents and small molecule inhibitors aiming at specific cytokines and intracellular signal pathways. However, such current therapeutic strategies can rarely induce recovery of immune tolerance in autoimmune disease patients. To overcome limitations of conventional treatment modalities, novel approaches using specific cell populations with immune-regulatory properties have been attempted to attenuate autoimmunity. Recently progressed biotechnologies enable sufficient in vitro expansion and proper manipulation of such 'tolerogenic' cell populations to be considered for clinical application. We introduce 3 representative cell types with immunosuppressive features, including mesenchymal stromal cells, Tregs, and myeloid-derived suppressor cells. Their cellular definitions, characteristics, mechanisms of immune regulation, and recent data about preclinical and clinical studies in systemic autoimmune diseases are reviewed here. Challenges and limitations of each cell therapy are also addressed.