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| 1 | From basic researches to new achievements in therapeutic strategies of KRAS-driven cancers显示文摘Among the numerous oncogenes involved in human cancers, KRAS represents the most studied and best characterized cancerrelated genes.Several therapeutic strategies targeting oncogenic KRAS(KRASonc) signaling pathways have been suggested,including the inhibition of synthetic lethal interactions, direct inhibition of KRASonc itself, blockade of downstream KRASonc effectors, prevention of post-translational KRASonc modifications, inhibition of the induced stem cell-like program, targeting of metabolic peculiarities, stimulation of the immune system, inhibition of inflammation, blockade of upstream signaling pathways,targeted RNA replacement, and oncogene-induced senescence.Despite intensive and continuous efforts, KRASonc remains an elusive target for cancer therapy.To highlight the progress to date, this review covers a collection of studies on therapeutic strategies for KRAS published from 1995 to date.An overview of the path of progress from earlier to more recent insights highlight novel opportunities for clinical development towards KRASonc-signaling targeted therapeutics. | Mahsa Saliani Razieh Jalal Mohammad Reza Ahmadian | 2019 | Cancer Biology & Medicine2019，16，3： | 2 |
| 2 | Development of a miniaturized 3D organoid culture platform for ultra-high-throughput screening显示文摘The recent advent of robust methods to grow human tissues as 3D organoids allows us to recapitulate the 3D architecture of tumors in an in vitro setting and offers a new orthogonal approach for drug discovery.However,organoid culturing with extracellular matrix to support 3D architecture has been challenging for high-throughput screening(HTS)-based drug discovery due to technical difficulties.Using genetically engineered human colon organoids as a model system,here we report our effort to miniaturize such 3D organoid culture with extracellular matrix support in high-density plates to enable HTS.We first established organoid culturing in a 384-well plate format and validated its application in a cell viability HTS assay by screening a 2036-compound library.We further miniaturized the 3D organoid culturing in a 1536-well ultra-HTS format and demonstrated its robust performance for large-scale primary compound screening.Our miniaturized organoid culturing method may be adapted to other types of organoids.By leveraging the power of 3D organoid culture in a high-density plate format,we provide a physiologically relevant screening platform to model tumors to accelerate organoid-based research and drug discovery. | Yuhong Du Xingnan Li Qiankun Niu Xiulei Mo Min Qui Tingxuan Ma Calvin J.Kuo Haian Fu | 2020 | Journal of Molecular Cell Biology2020，12，8： | 1 |
| 3 | 协同致死筛选技术及其在肿瘤相关领域研究中的应用和进展显示文摘最近10年协同致死筛选技术被成功应用到肿瘤相关领域的研究,成为揭示肿瘤相关基因与其他基因相互作用的有力手段。本文介绍了协同致死筛选的技术以及其在肿瘤相关领域研究中的应用和研究进展。研究发现了大量与常见癌基因如RAS、多聚ADP核糖聚合基因、MYC或抑癌基因P53、张力蛋白同源基因存在协同致死关系的基因,筛选还发现了化疗药物如紫杉醇、长春新碱和拓扑替康等的增敏基因。这些研究为揭示肿瘤耐药、复发机制提供了线索,为靶向抗肿瘤药物的联合应用提供了依据。本文综述了目前相对成熟的协同致死筛选的几种不同的技术方法,以及该技术用于抗肿瘤药物研发的研究进展。 | 王莉莉 李菲菲 赵长琦 | 2013 | 中国药理学与毒理学杂志2013，27，6： | 0 |
| 4 | Development of synthetic lethality in cancer:molecular and cellular classification显示文摘Recently,genetically targeted cancer therapies have been a topic of great interest.Synthetic lethality provides a new approach for the treatment of mutated genes that were previously considered unable to be targeted in traditional genotype-targeted treatments.The increasing researches and applications in the clinical setting made synthetic lethality a promising anticancer treatment option.However,the current understandings on different conditions of synthetic lethality have not been systematically assessed and the application of synthetic lethality in clinical practice still faces many challenges.Here,we propose a novel and systematic classification of synthetic lethality divided into gene level,pathway level,organelle level,and conditional synthetic lethality,according to the degree of specificity into its biological mechanism.Multiple preclinical findings of synthetic lethality in recent years will be reviewed and classified under these different categories.Moreover,synthetic lethality targeted drugs in clinical practice will be briefly discussed.Finally,we will explore the essential implications of this classification as well as its prospects in eliminating existing challenges and the future directions of synthetic lethality. | Shijie Li Win Topatana Sarun Juengpanich Jiasheng Cao Jiahao Hu Bin Zhang Diana Ma Xiujun Cai Mingyu Chen | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 5 | Synthetic Lethal Interactions Prediction Based on Multiple Similarity Measures Fusion显示文摘The synthetic lethality(SL)relationship arises when a combination of deficiencies in two genes leads to cell death,whereas a deficiency in either one of the two genes does not.The survival of the mutant tumor cells depends on the SL partners of the mutant gene,thereby the cancer cells could be selectively killed by inhibiting the SL partners of the oncogenic genes but normal cells could not.Therefore,there is an urgent need to develop more efficient computational methods of SL pairs identification for cancer targeted therapy.In this paper,we propose a new approach based on similarity fusion to predict SL pairs.Multiple types of gene similarity measures are integrated and/c-nearest neighbors algorithm(k-NN)is applied to achieve the similarity-based classification task between gene pairs.As a similarity-based method,our method demonstrated excellent performance in multiple experiments.Besides the effectiveness of our method,the ease of use and expansibility can also make our method more widely used in practice. | Lian-Lian Wu Yu-Qi Wen Xiao-Xi Yang Bo-Wei Yan Song He Xiao-Chen Bo | 2021 | Journal of Computer Science & Technology2021，36，2： | 0 |
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