This early phase I trial studies the side effects of implanting and removing a microdevice in patients with sarcomas that have spread to other places in the body (metastatic) or have come back (recurrent). Microdevices are rice-sized devices that are implanted into tumor tissue and are loaded with 10 different drugs that are delivered at very small doses, or "microdoses," which may only affect a very small, local area inside the tumor. The purpose of this study is to determine which drugs delivered in the microdevice affect tumor tissue in patients with sarcomas.

开始日期2025-01-31

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT06658093 / Not yet recruiting早期临床1期IIT

RESTOR [Rapamycin and Everolimus Study Towards Older Rejuvenation]: An Exploratory PK/PD Study of mTOR Inhibition in Older Human Subjects

As people get older, there are changes in their cells and tissues that may affect their ability to function. This can lead to increased death and age-associated disorders, like heart disease, cancer, and Alzheimer's disease. Studies in animal models have been able to identify drugs that slow the aging process, leading to a longer, healthier life. This study is focused on one such family of drugs, called mTOR inhibitors, and the investigators' goal is to test two of these drugs, Rapamycin (Sirolimus) and Everolimus (Afinitor), in healthy older adults to find a dose and dose timing that can be used to safely inhibit mTOR to the levels seen in young healthy persons. The investigators expect that the dose that works well in women may differ from the one that is best in men, so it is important to include both sexes in this research.

开始日期2025-01-01

申办/合作机构

University of Texas Health Science Center At San Antonio

[+1]

100 项与 mTORC2 相关的临床结果

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100 项与 mTORC2 相关的转化医学

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0 项与 mTORC2 相关的专利（医药）

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47,782

项与 mTORC2 相关的文献（医药）

2025-12-01·Journal of Clinical Immunology

Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS)

Article

作者: Yu, Meiping ; Wu, Bingbing ; Zhu, Li ; Chen, Yao ; Wang, Chenghao ; Li, Qifan ; Qian, Feng ; Zhou, Weitao ; Liu, Luyao ; Wu, Qi ; Hui, Xiaoying ; Hou, Jia ; Zhou, Qinhua ; Sun, Bijun ; Wang, Xiaochuan ; Wang, Ying ; Sun, Jinqiao ; Ying, Wenjing ; Wang, Wenjie

OBJECTIVEFAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism.METHODSWhole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis.RESULTSThe patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA⁺HLA-DR⁺, with high expression of CD85j, PD-1, and CD57. The percentage of Th1, Tfh, and autoreactive B cells were significantly increased in the patient. The abnormal immunophenotyping was partially attenuated by sirolimus treatment.CONCLUSIONSWe identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus.

2025-04-01·Neural Regeneration Research

Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

Article

作者: Li, Yingjia ; Ji, Yunxiang ; Xu, Chuanhui ; Wang, Yezhong ; Ye, Yongyi ; Luo, Wanxian ; Li, Linxi

JOURNAL/nrgr/04.03/01300535-202504000-00032/figure1/v/2024-07-06T104127Z/r/image-tiff Microglia, the primary immune cells within the brain, have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system, including Parkinson’s disease. Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity, but also exhibit remarkable anti-inflammatory properties. However, the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood. In this study, we developed perfluoropentane-based oxygen-loaded nanodroplets (PFP-OLNDs) and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo, and suppressed microglial activation in a mouse model of Parkinson’s disease. Microglial suppression led to a reduction in the inflammatory response, oxidative stress, and cell migration capacity in vitro. Consequently, the neurotoxic effects were mitigated, which alleviated neuronal degeneration. Additionally, ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming. We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α pathway. Collectively, our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

2025-03-01·Biomaterials

Maintaining myoprotein and redox homeostasis via an orally recharged nanoparticulate supplement potentiates sarcopenia treatment

Article

作者: Song, Xiaoyu ; Xu, Yingxi ; Xie, Xiaochun ; Wang, Xiaoxun ; Sun, Huayi ; Yu, Yang ; Huang, Runnian ; Cao, Liu ; Ma, Chunhua ; Wang, Difei ; Sun, Chen ; Chen, Fangman ; Yuan, Xiaoyue ; Xun, Zhe ; Jiang, Xuehan ; Yu, Tianhao ; Shao, Dan ; Shi, Xuetao ; Li, Yibai ; Liu, Xu ; Liu, Xiyan

Sarcopenia is a progressive skeletal muscle disorder characterized by the accelerated loss of muscle mass and function, with no promising pharmacotherapies. Understanding the imbalance of myoprotein homeostasis within myotubes, which causes sarcopenia, may facilitate the development of novel treatments for clinical use. In this study, we found a strong correlation between low serum selenium levels and muscle function in elderly patients with sarcopenia. We hypothesized that supplementation with selenium might be beneficial for the management of sarcopenia. To verify this hypothesis, we developed diselenide-bridged mesoporous silica nanoparticles (Se-Se-MSNs) with ROS-responsive degradation and release to supplement selenium. Se-Se-MSNs outperformed free selenocysteine in alleviating sarcopenia in both dexamethasone (Dex)- and denervation-induced mouse models. Subsequently, Se-Se-MSNs were loaded with leucine (Leu@Se-Se-MSNs), another nutritional supplement used in sarcopenia management. Oral administration of Leu@Se-Se-MSNs restored myoprotein homeostasis by enhancing mTOR/S6K signaling and inactivating Akt/FoxO3a/MuRF1 signaling, thus exerting optimal therapeutic effects against sarcopenia and exhibiting a more favorable in vivo safety profile. This study provides a proof of concept for treating sarcopenia by maintaining myoprotein and redox homeostasis simultaneously and offers valuable insights into the development of multifunctional nanoparticle-based supplements for sarcopenia management.

705

项与 mTORC2 相关的新闻（医药）

2024-10-31

·生物探索

Immunity | 抑制性共受体Lag3通过限制Myc依赖的代谢程序调节Treg细胞功能

引言调节性T（Treg）细胞是免疫系统中的一种特殊T细胞亚群，负责维持免疫耐受性和防止自身免疫性疾病的发生。它们通过抑制过度的免疫反应，避免对自身组织发起攻击。Treg细胞特异性表达Foxp3转录因子，并通过分泌抑制性细胞因子（如IL-10和TGF-β）或直接与其他免疫细胞接触来抑制其活性【1】。Treg细胞在控制慢性炎症、预防自身免疫性疾病以及调节肿瘤微环境中都发挥着重要作用【2】。Treg细胞表达一系列表面受体，其中Lag3是一种类似于CD4的共受体，主要在活化的T细胞和Treg细胞中表达【3】。Lag3被认为是一种抑制性共受体，能够限制常规T细胞的增殖和IL-2的产生。有研究报道，Lag3缺陷的Treg细胞不能缓解自身免疫性脑脊髓炎，但是Lag3可能会限制自身免疫性糖尿病中Treg细胞的增殖和功能【4,5】。虽然Lag3对Treg细胞功能的调节已经被证实，但是Lag3调节Treg细胞的确切机制仍不清楚。近日，来自美国西北大学范伯格医学院的Booki Min课题组在Immunity上发表了研究论文Inhibitory co-receptor Lag3 supports Foxp3+ regulatory T cell function by restraining Myc-dependent metabolic programming。在本研究中，作者特异性突变Treg细胞的Lag3受体，揭示了Lag3通过PI3K-Akt通路抑制Myc的表达，从而支持Treg细胞免疫抑制功能的分子机制。为了探究Lag3在Treg细胞功能调节中具体作用，研究人员在Lag3基因位点引入了loxP位点，将Lag3基因的1-3号外显子进行flox处理，然后与Foxp3CreYFP小鼠进行交配，构建了在Treg细胞中特异性缺陷Lag3的突变（Treg△Lag3E1-3）小鼠。通过诱导实验性自身免疫性脑脊髓炎（EAE），研究发现相较于野生型小鼠，Treg△Lag3E1-3小鼠的疾病进展更快且症状更严重，表现为中枢神经系统（CNS）中Treg细胞和CD4 T细胞浸润增加，促炎细胞因子也显著增加。这些结果表明，Lag3缺失的Treg细胞功能异常，未能有效控制EAE的发展。同时，研究人员还进一步的验证了Lag3在免疫抑制和肿瘤生长调控中的作用。总的来说，Lag3在维持Treg细胞的抑制功能和调节免疫反应方面发挥重要作用，其缺失可能导致更严重的炎症反应和免疫失调。接下来，为了揭示Lag3调节Treg细胞功能的具体机制，研究人员先对CNS中分离的Treg细胞进行了RNA-seq分析。研究发现，代谢过程是Lag3缺失的Treg细胞中主要富集的途径。GSEA分析进一步确认，Lag3缺失的Treg细胞中上调的基因高度富集在细胞代谢途径中，包括Myc靶基因、氧化磷酸化、糖酵解和脂肪酸代谢途径。Myc是多种细胞代谢过程的关键调节因子，它直接激活几乎所有编码糖酵解酶的基因。在Lag3缺失的Treg细胞中，Myc表达高于对照组且与糖酵解相关的基因表达显著增加，与此相对应的是糖酵解活性增加。此外，在Lag3缺失的Treg细胞中敲低Myc的表达，糖酵解活性受到明显抑制，Treg细胞的免疫抑制功能得到恢复。研究人员还探究了Lag3抑制Myc表达的分子机制。他们发现Lag3胞质结构域缺失导致Myc及其代谢靶基因的过度表达，进而引发Treg细胞的代谢失调。这些结果表明，Lag3通过控制Myc的表达来调节Treg细胞的代谢和功能，Myc相关的代谢变化直接影响Treg细胞在体内的抑制功能。研究人员还探究了Lag3抑制Myc表达的分子机制。他们发现Lag3胞质结构域缺失导致Myc及其代谢靶基因的过度表达，进而引发Treg细胞的代谢失调。之前的研究表明，PI3K-Akt信号通路在调控Myc表达中起重要作用，并且Lag3缺失在其他T细胞中能增强Akt磷酸化。因此作者推测Lag3可能通过PI3K-Akt信号通路抑制了Treg细胞中Myc的表达。为了证实这个推测，研究人员分析了Lag3缺失的Treg细胞中PI3K信号的激活情况以及使用PI3K-Akt通路的相关抑制剂处理细胞。结果表明，Lag3突变导致的PTEN下调、Rictor上调和Akt的异常磷酸化共同作用，引发Treg细胞的代谢失调和抑制功能减弱。当抑制PI3K和Rictor可以有效降低Myc的表达，恢复Lag3缺失的Treg细胞正常代谢活动，并改善其免疫抑制功能。文章的最后，研究人员详细的分析了Lag3对Myc的调控是如何影响Treg细胞的代谢活动。前面介绍到Lag3的缺失会导致Treg细胞的糖酵解活性增强，一个显著特征是细胞外酸化率增加，而乳酸脱氢酶A（Ldha）是介导这种状况发生的关键基因，并且Ldha也是Myc的靶基因之一。因此，研究人员对Ldha的功能进行了分析。结果表明，Lag3缺失会导致Ldha的表达增加，这与Myc的表达升高相一致，乳酸分泌也随之增加。抑制Ldha的活性能够恢复Lag3缺失导致的Treg细胞功能障碍以及代谢异常，从而揭示了Myc-Ldha轴在Treg细胞功能中的关键作用。模式图（Credit: Immunity）总的来说，这篇文章揭示了Lag3共受体调节Treg细胞免疫抑制功能的具体机制，Lag3通过PI3K-Akt信号通路抑制Myc的表达，当Lag3缺失后Myc表达升高并激活下游代谢基因的表达，改写了Treg细胞的代谢进而影响了Treg细胞的抑制性功能。参考文献 1. Sakaguchi, S., Yamaguchi, T., Nomura, T., and Ono, M. (2008). Regulatory T cells and immune tolerance. Cell 133, 775–787. 2. Vignali, D.A.A., Collison, L.W., and Workman, C.J. (2008). How regulatory T cells work. Nat. Rev. Immunol. 8, 523–532. 3. Andrews, L.P., Marciscano, A.E., Drake, C.G., and Vignali, D.A.A. (2017). LAG3 (CD223) as a cancer immunotherapy target. Immunol. Rev. 276, 80–96. 4. Kim, D., Le, H.T., Nguyen, Q.T., Kim, S., Lee, J., and Min, B. (2019). Cutting Edge: IL-27 Attenuates Autoimmune Neuroinflammation via Regulatory T Cell/Lag3-Dependent but IL-10-Independent Mechanisms In Vivo. J. Immunol. 202, 1680–1685. 5. Zhang, Q., Chikina, M., Szymczak-Workman, A.L., Horne, W., Kolls, J.K., Vignali, K.M., Normolle, D., Bettini, M., Workman, C.J., and Vignali, D.A.A. (2017). LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes. Sci. Immunol. 2, eaah4569. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.immuni.2024.08.008 责编|探索君排版|探索君来源|BioArt End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

AACR会议临床结果临床1期免疫疗法临床终止

2024-10-26

·生物探索

Cell Metab | 李珂团队合作揭示脂肪细胞谷胱甘肽在肥胖乳腺癌进展中的关键作用

引言肥胖是多种癌症类型的一个主要的诱因【1】。在与肥胖相关的女性癌症中，乳腺癌是导致死亡的主要原因【2-4】。既往研究表明，肥胖能够诱导乳腺肿瘤微环境（TME）的代谢改变和以脂肪为主的局部修饰从而促进癌症进展【5】。然而肥胖诱导的肿瘤微环境代谢物对乳腺癌生长和转移的影响尚不清楚，因此探究肥胖与乳腺癌之间的串扰因素及机制对改善肥胖乳腺癌患者的治疗效果至关重要。 2024年10月22日，中国医学科学院&北京协和医学院医药生物技术研究所李珂团队及李卓荣团队在Cell Metabolism杂志上发表题为Adipocyte-Derived Glutathione Promotes Obesity-Related Breast Cancer by Regulating the SCARB2-ARF1-mTORC1 Complex的研究论文【6】。李珂团队长期致力于乳腺癌发生发展的分子机制探究。先前研究成果表明，FGD5通过维持肿瘤起始细胞样性状促进基底样乳腺癌发生和发展【7】。本研究发现高脂饮食（HFD）诱导脂肪细胞谷胱甘肽（GSH）分泌增多，GSH通过经典摄入转运体进入肿瘤细胞，通过溶酶体膜表面的溶酶体膜蛋白2（SCARB2）活化mTORC1信号通路，促进肥胖相关乳腺癌的进展。作者首先建立了饮食诱导肥胖（DIO）的小鼠模型研究肥胖对乳腺癌进展的影响。相较于正常膳食组（NCD），HFD组小鼠表现出更快的肿瘤生长速度，且瘤体积更大，肺部转移更为严重。于是，作者检测了NCD和HFD组小鼠的肿瘤微环境（TME）代谢产物，从中筛选出了十个差异最为显著的代谢物，并通过体外和体内实验确定了代谢物中GSH的促肿瘤作用。有趣的是，作者发现，抑制肿瘤细胞内部的GSH生成对于肥胖相关乳腺癌的进展没有显著影响，这提示肿瘤微环境中的GSH可能是肥胖促乳腺癌进展的主要因素。为了阐明GSH的来源，作者对小鼠肿瘤组织进行了多重免疫荧光染色，发现GSH在HFD小鼠肿瘤组织的脂肪细胞（脂联素阳性）中有较强的聚集。此外，作者观察到肥胖乳腺癌患者的脂肪细胞而不是肿瘤细胞表现出比非肥胖患者更高水平的谷氨酸半胱氨酸连接酶（GCLC），表明肥胖患者脂肪细胞中GSH合成的能力增强。此外，与非肥胖患者相比，肥胖乳腺癌患者的脂肪细胞和肿瘤细胞显示出更高水平的GSH。随后作者利用sgRNA敲低前脂肪细胞（3T3-L1）中GCLC的内源性表达，用以上脂肪细胞的培养上清培养乳腺癌细胞，发现脂肪细胞分泌物能够促进乳腺癌细胞的增殖和侵袭，而GCLC缺失组促乳腺癌增殖和侵袭的能力减弱。最终，作者建立了脂肪细胞特异性缺失GCLC的转基因小鼠模型，发现脂肪细胞GSH合成能力受损阻碍HFD的促乳腺癌进展作用。据此作者推测脂肪细胞在肿瘤微环境中分泌的GSH是肥胖促进相关乳腺癌进展的关键因素。随后，作者关注GSH促进乳腺癌进展的机制，发现GSH能够进入肿瘤细胞，并定位于溶酶体表面。基于质谱法（MS）的蛋白质组学分析、RNA-seq分析和生化分析，作者发现GSH与溶酶体膜表面蛋白SCARB2结合进而激活mTORC1信号通路。并探索了GSH诱导mTOR的激活机制，发现GSH干扰SCARB2蛋白的N末端与C末端相互作用，促使SCARB2的N端暴露从而与GTP酶ARF1结合，促进了ARF1和mLST8的相互作用以募集mTORC1溶酶体定位，从而活化mTORC1信号通路。模式图（Credit: Cell Metabolism）综上所述，HFD导致脂肪细胞GSH分泌增多，外源性GSH进入肿瘤细胞后，与溶酶体膜表面SCARB2结合，并通过SCARB2-ARF1复合物激活mTORC1信号通路，从而促进肥胖相关乳腺癌的进展。该研究揭示了脂肪细胞来源的GSH在肥胖加速乳腺癌进展中的作用；阐明了GSH介导mTORC1活化的全新形式；并首次提出SCARB2作为GSH的新型传感器在调节mTORC1信号通路的作用。这些发现强调了靶向GSH/SCARB2/ARF1/mTOR轴能够为肥胖乳腺癌患者的有效治疗提供潜在策略。参考文献 1. Lauby-Secretan, B., C. Scoccianti, D. Loomis, Y. Grosse, F. Bianchini, K. Straif, and G. International Agency for Research on Cancer Handbook Working. (2016). Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 375, 794-8. https://doi-org.libproxy1.nus.edu.sg/10.1056/NEJMsr1606602 2. Reaves, D.K., E. Ginsburg, J.J. Bang, and J.M. Fleming. (2015). Persistent organic pollutants and obesity: are they potential mechanisms for breast cancer promotion? Endocr Relat Cancer. 22, R69-86. https://doi-org.libproxy1.nus.edu.sg/10.1530/ERC-14-0411 3. Bray, F., J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, and A. Jemal. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68, 394-424. https://doi-org.libproxy1.nus.edu.sg/10.3322/caac.21492 4. White, A.J., H.B. Nichols, P.T. Bradshaw, and D.P. Sandler. (2015). Overall and central adiposity and breast cancer risk in the Sister Study. Cancer. 121, 3700-8. https://doi-org.libproxy1.nus.edu.sg/10.1002/cncr.29552 5. Sanchez-Jimenez, F., A. Perez-Perez, L. de la Cruz-Merino, and V. Sanchez-Margalet. (2019). Obesity and Breast Cancer: Role of Leptin. Front Oncol. 9, 596. https://doi-org.libproxy1.nus.edu.sg/10.3389/fonc.2019.00596 6. Chenxi Zhao, T.Z., Si-tu Xue, Peitao Zhang, Feng Wang, Yunxuan Li, Ying Liu, Luyao Zhao, Jie Wu, Yechao Yan, Xiaoyun Mao, Yuping Chen, Jian Yuan, Zhuorong Li, and Ke Li. (2024). Adipocyte-derived glutathione promotes obesity-related breast cancer by regulating the SCARB2-ARF1- mTORC1 complex. Cell Metabolism. https://doi-org.libproxy1.nus.edu.sg/https://doi.org/10.1016/j.cmet.2024.09.013 7. Li, K., T.T. Zhang, C.X. Zhao, F. Wang, B. Cui, Z.N. Yang, X.X. Lv, Z. Yeerjiang, Y.F. Yuan, J.M. Yu, Z.H. Wang, X.W. Zhang, J.J. Yu, S.S. Liu, S. Shang, B. Huang, F. Hua, and Z.W. Hu. (2021). Faciogenital Dysplasia 5 supports cancer stem cell traits in basal-like breast cancer by enhancing EGFR stability. Sci Transl Med. 13. https://doi-org.libproxy1.nus.edu.sg/10.1126/scitranslmed.abb2914 https://www-cell-com.libproxy1.nus.edu.sg/cell-metabolism/abstract/S1550-4131(24)00395-4 责编|探索君排版|探索君来源|BioArt End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

临床研究

2024-10-26

·GlobeNewswire-Health Care

Kura Oncology to Present New Data Supporting Combination of KO-2806 with KRAS G12C and Pan-RAS Inhibitors

– New preclinical data to be presented at EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics – Oct. 23, 2024 -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced the upcoming presentation of new preclinical data supporting the combination of its next-generation farnesyl transferase inhibitor (FTI) KO-2806 with targeted therapies, including KRASG12C inhibitors and pan-RAS inhibitors, at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. “We look forward to presenting an update to our growing body of preclinical and clinical data that demonstrate the potential of KO-2806 as a companion therapeutic to augment the antitumor activities of KRASG12C and pan-RAS inhibitors,” said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. “These findings support the promising therapeutic strategy of blunting the effects of innate and adaptive resistance to targeted agents to treat cancers driven by KRAS mutations, including KRASG12C non-small cell lung cancer (NSCLC) and KRAS-mutant colorectal cancers. If successful, we believe KO-2806 could drive enhanced antitumor activity and become a combination partner to multiple targeted therapies in large solid tumor indications.” Details for the session titles and information for the two abstracts are listed below. Copies of the presentations will be available in the Posters and Presentations section on Kura’s website following presentation at the conference. KO-2806, a next-generation farnesyl transferase inhibitor, re-sensitizes KRAS G12C NSCLC tumors to KRAS G12C mutant-specific inhibitors through mTOR signaling inhibition Session Date and Time: Friday, October 25, 2024; 9:00 AM - 3:00 PM ET Session and Location: Drug Resistance and Modifiers, Exhibition Hall Poster Number: PB376 The next-generation farnesyl transferase inhibitor KO-2806 sensitizes colorectal cancers to pan-RAS inhibition Session Date and Time: Friday, October 25, 2024; 9:00 AM - 3:00 PM ET Session and Location: Drug Resistance and Modifiers, Exhibition Hall Poster Number: PB378 KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon the potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. At the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Kura presented preclinical data supporting the rationale for combining KO-2806 with distinct classes of targeted therapies, including tyrosine kinase inhibitors, KRASG12C inhibitors and KRASG12D inhibitors. Kura is evaluating KO-2806 in a Phase 1 dose-escalation trial (FIT-001) as a monotherapy, in combination with cabozantinib in clear cell renal cell carcinoma and in combination with adagrasib in KRASG12C NSCLC. Additional information about clinical trials for KO-2806 can be found at https://kuraoncology.com/clinical-trials/#farnesyl-transferase-inhibitor. Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib, a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction, has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory (R/R) NPM1-mutant AML. Kura has completed enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-mutant AML (KOMET-001). The Company is also conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML. Kura is evaluating KO-2806, a next-generation FTI, in a Phase 1 dose-escalation trial as a monotherapy and in combination with targeted therapies (FIT-001). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma (KURRENT-HN). For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on Twitter and LinkedIn. The content above comes from the network. if any infringement, please contact us to modify.