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  • Open Access

    REVIEW

    Development of PROTACS degrading KRAS and SOS1

    GERHARD HAMILTON*, MARIE-THERESE EGGERSTORFER, SANDRA STICKLER

    Oncology Research, Vol.32, No.8, pp. 1257-1264, 2024, DOI:10.32604/or.2024.051653 - 17 July 2024

    Abstract The Kirsten rat sarcoma virus—son of sevenless 1 (KRAS-SOS1) axis drives tumor growth preferentially in pancreatic, colon, and lung cancer. Now, KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of KRAS. However, the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%, lasting for a mean period of 8 months. One approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras (PROTACs), which… More > Graphic Abstract

    Development of PROTACS degrading KRAS and SOS1

  • Open Access

    REVIEW

    Targeting KRAS in pancreatic cancer

    SANDRA STICKLER, BARBARA RATH, GERHARD HAMILTON*

    Oncology Research, Vol.32, No.5, pp. 799-805, 2024, DOI:10.32604/or.2024.045356 - 23 April 2024

    Abstract Pancreatic cancer has a dismal prognosis due to late detection and lack of efficient therapies. The Kirsten rat sarcoma virus (KRAS) oncogene is mutated in up to 90% of all pancreatic ductal adenocarcinomas (PDACs) and constitutes an attractive target for therapy. However, the most common KRAS mutations in PDAC are G12D (44%), G12V (34%) and G12R (20%) that are not amenable to treatment by KRAS G12C-directed cysteine-reactive KRAS inhibitors such as Sotorasib and Adagrasib that exhibit clinical efficacy in lung cancer. KRAS G12C mutant pancreatic cancer has been treated with Sotorasib but this mutation is More >

  • Open Access

    ARTICLE

    Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

    XINFENG ZHANG1,2,#, SHUANG LI2,#, MEIRU SONG1,2, YUE CHEN3, LIANGZHENG CHANG3, ZHERUI LIU4, HONGYUAN DAI3, YUTAO WANG4, GANGQI YANG3, YUN JIANG5,6,*, YINYING LU1,2,*

    Oncology Research, Vol.32, No.4, pp. 679-690, 2024, DOI:10.32604/or.2024.046231 - 20 March 2024

    Abstract Liver cancer is a prevalent malignant cancer, ranking third in terms of mortality rate. Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer. Hepatocellular carcinoma (HCC) has low expression of focal adhesion kinase (FAK), which increases the risk of metastasis and recurrence. Nevertheless, the efficacy of FAK phosphorylation inhibitors is currently limited. Thus, investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis. This study examined the correlation between FAK expression and the prognosis of HCC. Additionally,… More >

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