A PDX model combined with CD-DST assay to evaluate the antitumor properties of KRpep-2d and oxaliplatin in KRAS (G12D) mutant colorectal cancer

Li, Wuguo; Chen, Wei; Wang, Jialin; Zhao, Guochao; Chen, Lianzhou; Wan, Yong; Luo, Qianxin; Li, Wenwen; Huang, Haoji; Yang, Yutong; Chen, Daici; Qiao, Shan

doi:10.1016/j.heliyon.2022.e12518

Cited by 2 publications

(3 citation statements)

References 40 publications

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“…Similarly, the G12D‐targeting pathway is peptide KRpep‐2d. Similarly, peptide KRpep‐2d, a G12D‐targeting inhibitor, had no significant antitumor effect on the PDX model, while oxaliplatin showed a significant inhibitory effect 249 . The failure of KRpep‐2d is suspected to be related to bioavailability and stability 250 .…”

Section: Combination Strategies Adapted To Specific Mutations In Diff...mentioning

confidence: 99%

“…Similarly, peptide KRpep‐2d, a G12D‐targeting inhibitor, had no significant antitumor effect on the PDX model, while oxaliplatin showed a significant inhibitory effect. 249 The failure of KRpep‐2d is suspected to be related to bioavailability and stability. 250 Additionally, the combination of binimetinib, hydroxychloroquine, and bevacizumab makes a 17% reduction in lung metastasis size in FOLFOX‐resistant patients after 6 weeks treatment with this combination with FOLFOX.…”

Section: Combination Strategies Adapted To Specific Mutations In Diff...mentioning

confidence: 99%

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RAS‐targeted cancer therapy: Advances in drugging specific mutations

Liu

Yang

et al. 2023

MedComm

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Rat sarcoma (RAS), as a frequently mutated oncogene, has been studied as an attractive target for treating RAS-driven cancers for over four decades. However, it is until the recent success of kirsten-RAS (KRAS) G12C inhibitor that RAS gets rid of the title "undruggable". It is worth noting that the therapeutic effect of KRAS G12C inhibitors on different RAS allelic mutations or even different cancers with KRAS G12C varies significantly. Thus, deep understanding of the characteristics of each allelic RAS mutation will be a prerequisite for developing new RAS inhibitors. In this review, the structural and biochemical features of different RAS mutations are summarized and compared. Besides, the pathological characteristics and treatment responses of different cancers carrying RAS mutations are listed based on clinical reports. In addition, the development of RAS inhibitors, either direct or indirect, that target the downstream components in RAS pathway is summarized as well. Hopefully, this review will broaden our knowledge on RAS-targeting strategies and trigger more intensive studies on exploiting new RAS allele-specific inhibitors. K E Y W O R D Sallelic RAS mutation, cancer, personalized therapy, RAS inhibitor INTRODUCTIONRat sarcoma (RAS) proteins belong to the small-molecule G protein family. As binary molecular switch, RAS GTPases cycle between guanosine triphosphate (GTP)bound active form and guanosine diphosphate (GDP)bound inactive form, facilitating "on" or "off" state in signal transduction. There are three canonical RAS genes, kirsten-RAS (KRAS), neuroblastoma-RAS (NRAS), and harvey-RAS (HRAS), encoding four RAS proteins (KRAS4A, KRAS4B, NRAS, and HRAS). Among RAS

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Section: Combination Strategies Adapted To Specific Mutations In Diff...mentioning

confidence: 99%

Section: Combination Strategies Adapted To Specific Mutations In Diff...mentioning

confidence: 99%

RAS‐targeted cancer therapy: Advances in drugging specific mutations

Liu

Yang

et al. 2023

MedComm

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“…For this reason, compounds targeting other KRAS forms and pan-KRAS inhibitors are being developed. KRpep-2d [ 35 ] and KS-58 [ 36 , 37 ] were developed to target KRAS G12D mutation, while 12VC1 [ 38 ] is able to selectively recognize the active state of both G12V and G12C forms. VS-6766 (Avutometinib) is a dual RAF–MEK inhibitor that showed good therapeutic activity against KRAS G12V mutation and is under clinical evaluation (NCT03875820, Phase I, NCT04625270, Phase II) for different types of KRAS-mutated cancers [ 39 ].…”

Section: Actual Therapeutic Strategies Against Krasmentioning

confidence: 99%

The Nanotechnology-Based Approaches against Kirsten Rat Sarcoma-Mutated Cancers

Andrade,

German-Cortés,

Montero

et al. 2023

Pharmaceutics

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Kirsten rat sarcoma (KRAS) is a small GTPase which acts as a molecular switch to regulate several cell biological processes including cell survival, proliferation, and differentiation. Alterations in KRAS have been found in 25% of all human cancers, with pancreatic cancer (90%), colorectal cancer (45%), and lung cancer (35%) being the types of cancer with the highest mutation rates. KRAS oncogenic mutations are not only responsible for malignant cell transformation and tumor development but also related to poor prognosis, low survival rate, and resistance to chemotherapy. Although different strategies have been developed to specifically target this oncoprotein over the last few decades, almost all of them have failed, relying on the current therapeutic solutions to target proteins involved in the KRAS pathway using chemical or gene therapy. Nanomedicine can certainly bring a solution for the lack of specificity and effectiveness of anti-KRAS therapy. Therefore, nanoparticles of different natures are being developed to improve the therapeutic index of drugs, genetic material, and/or biomolecules and to allow their delivery specifically into the cells of interest. The present work aims to summarize the most recent advances related to the use of nanotechnology for the development of new therapeutic strategies against KRAS-mutated cancers.

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A PDX model combined with CD-DST assay to evaluate the antitumor properties of KRpep-2d and oxaliplatin in KRAS (G12D) mutant colorectal cancer

Cited by 2 publications

References 40 publications

RAS‐targeted cancer therapy: Advances in drugging specific mutations

RAS‐targeted cancer therapy: Advances in drugging specific mutations

The Nanotechnology-Based Approaches against Kirsten Rat Sarcoma-Mutated Cancers

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