• Title/Summary/Keyword: Molecular Targeted Therapy

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Pre- and Post-Treatment Imaging of Primary Central Nervous System Tumors in the Molecular and Genetic Era

  • Sung Soo Ahn;Soonmee Cha
    • Korean Journal of Radiology
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    • v.22 no.11
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    • pp.1858-1874
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    • 2021
  • Recent advances in the molecular and genetic characterization of central nervous system (CNS) tumors have ushered in a new era of tumor classification, diagnosis, and prognostic assessment. In this emerging and rapidly evolving molecular genetic era, imaging plays a critical role in the preoperative diagnosis and surgical planning, molecular marker prediction, targeted treatment planning, and post-therapy assessment of CNS tumors. This review provides an overview of the current imaging methods relevant to the molecular genetic classification of CNS tumors. Specifically, we focused on 1) the correlates between imaging features and specific molecular genetic markers and 2) the post-therapy imaging used for therapeutic assessment.

Targeted Immunotherapy for Autoimmune Disease

  • Seung Min Jung;Wan-Uk Kim
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.9.1-9.23
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    • 2022
  • In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.

Ribozyme-Mediated Replacement of p53 RNA by Targeted Trans-Splicing

  • Shin, Kyung-Sook;Bae, Soo-Jin;Hwang, Eun-Seong;Jeong, Sun-Joo;Lee, Seong-Wook
    • Journal of Microbiology and Biotechnology
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    • v.12 no.5
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    • pp.844-848
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    • 2002
  • In more than half of human tumors, the p53 tumor suppressor gene is mutated. Thus, restoration of wild-type p53 activity by repair of mutant RNA could be a potentially promissing approach to cancer treatment. To explore the potential use of RNA repair for cancer therapy, trans-splicing group I ribozymes were developed that could replace mutant p53 RNA with RNA sequence attached to the 3'end of ribozymes. By employing a mapping library of ribozymes, we first determined which regions of the p53 RNA are accessible to ribozymes, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. Next, trans-splicing ribozymes were generated that specifically recognized the sequences around these accessible regions. Subsequently, the ribozymes reacted with and altered the p53 transcripts by transferring a 3'exon tag sequence onto the targeted p53 RNA with high fidelity. Thus, these ribozymes could be utilized to repair mutant p53 in tumors, which would revert the neoplastic phenotype.

Synthesis of a PEGylated tracer for radioiodination and evaluation of potential in tumor targeting

  • Abhinav Bhise;Sushil K Dwivedi;Kiwoong Lee;Jeong Eun Lim;Subramani Rajkumar;Woonghee Lee;Seong Hwan Cho;Jeongsoo Yoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.7 no.2
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    • pp.79-84
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    • 2021
  • Radiopharmaceuticals are important for tumor diagnosis and therapy. To deliver a radiotracer at the desired target excluding non-targeted tissues is difficult The development of a targeted tracer that has a good clearance profile while maintaining high biostability and biocompatibility is key to optimizing its biodistribution and transport across biological barriers. Improving the hydrophilicity of radiotracers by PEGylation can reduce serum binding, allowing the tracer to circulate without retention and reducing its affinity for non-targeted tissues. In this study, we synthesized a new benzamido tracer (SnBz-PEG36) with the introduction of a low molecular weight polyethylene glycol unit (PEG36, ~2,100 Da). The tumor targeting efficiency and biodistribution of [131I]-Bz-PEG36 or radiotracer-loaded liposomes were evaluated after their administration to normal mice or mouse tumor models including CT26 (xenograft) and 4T1 (xenograft and orthotopic). Most of the radiotracer was cleared out rapidly (1-24 h post-administration) through the kidney and there was little tumor uptake.

Molecular Therapy as a Future Strategy in Endometrial Cancer

  • Thanapprapasr, Duangmani;Thanapprapasr, Kamolrat
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3419-3423
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    • 2013
  • Of all gynecologic cancers, endometrial cancer is the most common cancer in the US and Europe. In addition, it is presently the second most common gynecologic cancer in the world. As a result of increasing menopausal, obese and tamoxifen use women, the incidence of the cancer seems to be on the increase. Surgery is the major treatment, whereas postoperative radiation therapy in high-intermediate risk patients many prevent locoregional recurrence. Adjuvant chemotherapy can improve progression free survival in advanced or recurrent cancers. Molecular targeted therapies are now a focus of attention including anti-vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) inhibitor and tyrosine kinase inhibitor (TKI). They may provide useful future strategies for control of endometrial malignancies in developing countries and across the world.

Radioiodination strategies for carborane compounds

  • Rajkumar Subramani;Abhinav Bhise;Jeongsoo Yoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.8 no.1
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    • pp.39-44
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    • 2022
  • The development of methods for the inert and stable radiohalogenation of targeted radiopharmaceuticals is a prerequisite for real-time diagnosis and therapy using radiohalogenated radiopharmaceuticals. Radiohalogenated carboranes demonstrate superior stability in vivo and versatile applications compared with directly labeled tyrosine analogues or synthetically modified organic compounds. Herein, we focus on the most common approaches for the radioiodination (123l, 124l, 125l, and 131l) of carborane derivatives.

Molecular Classification of Hepatocellular Carcinoma and Its Impact on Prognostic Prediction and Personized Therapy

  • Dhruba Kadel;Lun-Xiu Qin
    • Journal of Digestive Cancer Research
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    • v.5 no.1
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    • pp.5-15
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    • 2017
  • Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related death in the world. The aggressive but not always predictable pattern of HCC causes the limited treatment option and poorer outcome. Many researches had already proven the heterogeneity of HCC is one of the major challenges for treatment option and prognosis prediction. Molecular subtyping of HCC and selection of patient based on molecular profile can provide the optimization in the treatment and prognosis prediction. In this review, we have tried to summarize the molecular classification of HCC proposed by different valuable researches presented in the logistic way.

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MicroRNAs in Colorectal Cancer: from Diagnosis to Targeted Therapy

  • Orang, Ayla Valinezhad;Barzegari, Abolfazl
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.6989-6999
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    • 2014
  • Colorectal cancer (CRC) is one of the major healthcare problems worldwide and its processes of genesis include a sequence of molecular pathways from adenoma to carcinoma. The discovery of microRNAs, a subset of regulatory non-coding RNAs, has added new insights into CRC diagnosis and management. Together with several causes of colorectal neoplasia, aberrant expression of oncomiRs (oncogenic and tumor suppressor miRNAs) in cancer cells was found to be indirectly result in up- or down-regulation of targeted mRNAs specific to tumor promoter or inhibitor genes. The study of miRNAs as CRC biomarkers utilizes expression profiling methods from traditional tissue samples along with newly introduced non-invasive samples of faeces and body fluids. In addition, miRNAs could be employed to predict chemo- and radio-therapy responses and be manipulated in order to alleviate CRC characteristics. The scope of this article is to provide a comprehensive review of scientific literature describing aberrantly expressed miRNAs, and consequently dysregulation of targeted mRNAs along with the potential role of miRNAs in CRC diagnosis and prognosis, as well as to summarize the recent findings on miRNA-based manipulation methods with the aim of advancing in anti-CRC therapies.

Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

  • In-Ho Kim
    • Journal of Gastric Cancer
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    • v.24 no.1
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    • pp.29-56
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    • 2024
  • In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

Assessment of Appropriateness of Criteria for Insurance Coverage on Systemic Therapy used in Renal Cell Carcinoma (신세포암에 사용되는 전신 항암요법의 요양급여기준에 관한 고찰)

  • Kim, Jeong-Yeon;Park, Eun-Ji;Bae, Min-Kyung;Yoon, Jeong-Hyun
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.4
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    • pp.319-331
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    • 2011
  • Purpose: The purpose of this study is to evaluate current criteria for insurance coverage by Health Insurance Review & Assessment Service (HIRA) on the systemic therapy used in the treatment of advanced or metastatic renal cell carcinoma (RCC), by reviewing all available clinical evidences including a variety of clinical practice guidelines. Methods: We searched clinical databases and collected data from published phase 1 through 3 randomized clinical trials on all systemic therapies used in RCC, including novel targeted therapies. Additionally, current clinical practice guidelines on the management of kidney cancer or RCC were reviewed. Based on the collected data we evaluated the appropriateness of the HIRA criteria for insurance coverage on the systemic therapy of RCC whether they are evidence-based and up to date. Results: On the basis of the collected data we concluded that there was a need for a revision in HIRA criteria for systemic therapy of RCC. Despite recent emerging therapeutic advances and changes in therapeutic strategies of management of RCC, some of anticancer regimens were inappropriately listed even though they were not proven to provide efficacy or safety superior to those of other therapies. We thus proposed an updated recommendation based on current clinical evidences. Conclusion: Systemic therapy of RCC is being rapidly changed with the advancement of understanding of the molecular biology of cancer. Consequently newly developed targeted therapies are becoming the standard therapy in the management of medically or surgically unresectable advanced or metastatic RCC. To provide effective and safe therapy to patients with RCC, the criteria for insurance coverage should be made carefully taking into consideration of most up-to-date and high-quality clinical evidences, and should be continuously reviewed so as to reflect evidence-based clinical practice.