The advent of next-generation RAS inhibitors brings renewed optimism to the care of patients with pancreatic cancer after decades of failure for novel therapeutics. A recent study highlights the potent antitumour activity of the multi-selective RAS(ON) inhibitor RMC-7977 across a spectrum of preclinical pancreatic cancer models..

新一代RAS抑制剂的出现为胰腺癌患者的护理带来了新的乐观情绪，因为几十年来新疗法的失败。最近的一项研究强调了多选择性RAS（ON）抑制剂RMC-7977在一系列临床前胰腺癌模型中的有效抗肿瘤活性。。

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Fig. 1: Mutant KRAS drives oncogenesis in PDAC via cell-intrinsic and cell-extrinsic mechanisms.

图1：突变KRAS通过细胞内在和细胞外在机制驱动PDAC中的肿瘤发生。

ReferencesBuscail, L., Bournet, B. & Cordelier, P. Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer. Nat. Rev. Gastroenterol. Hepatol. 17, 153–168 (2020).Article

参考文献Buscail，L.，Bournet，B。＆Cordelier，P。致癌KRAS在胰腺癌的诊断，预后和治疗中的作用。胃肠病学国家修订版。肝病。17153-168（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kemp, S. B. et al. Efficacy of a small-molecule inhibitor of KrasG12D in immunocompetent models of pancreatic cancer. Cancer Discov. 13, 298–311 (2023).Article

Kemp，S.B.等人。KrasG12D小分子抑制剂在胰腺癌免疫活性模型中的功效。癌症发现。13298-311（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kim, D. et al. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature 619, 160–166 (2023).Article

Kim，D。等人。泛KRAS抑制剂禁用致癌信号传导和肿瘤生长。自然619160-166（2023）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jiang, J. et al. Translational and therapeutic evaluation of RAS-GTP inhibition by RMC-6236 in RAS-driven cancers. Cancer Discov. 14, 994–1017 (2024).Article

Jiang，J。等人。RMC-6236在RAS驱动的癌症中对RAS-GTP抑制的翻译和治疗评估。癌症发现。14994-1017（2024）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Arbour, K. C. et al. 652O preliminary clinical activity of RMC-6236, a first-in-class, RAS-selective, tri-complex RAS-MULTI(ON) inhibitor in patients with KRAS mutant pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) [abstract]. Ann. Oncol. 34, S458 (2023).Article .

Arbour，K.C.等[652O]。RMC-6236是一种一流的RAS选择性三复合RAS多（ON）抑制剂，在KRAS突变型胰腺导管腺癌（PDAC）和非小细胞肺癌（NSCLC）患者中的初步临床活性[摘要]。安科。34，S458（2023）。文章。

Google Scholar

谷歌学者

Wasko, U. N. et al. Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer. Nature 629, 927–936 (2024).Article

Wasko，U.N.等人。胰腺癌中RAS-GTP抑制的肿瘤选择性活性。自然629927-936（2024）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Holderfield, M. et al. Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. Nature 629, 919–926 (2024).Article

Holderfield，M.等人。同时抑制致癌和野生型RAS-GTP用于癌症治疗。自然629919-926（2024）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Mahadevan, K. K. et al. KRASG12D inhibition reprograms the microenvironment of early and advanced pancreatic cancer to promote FAS-mediated killing by CD8 + T cells. Cancer Cell 41, 1606–1620.e8 (2023).Article

Mahadevan，K.K。等人，KRASG12D抑制重编程早期和晚期胰腺癌的微环境，以促进CD8+T细胞介导的FAS介导的杀伤。癌细胞411606-1620.e8（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Pant, S. et al. Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. Nat. Med. 30, 531–542 (2024).Article

Pant，S.等人。胰腺癌和结直肠癌中淋巴结靶向的mKRAS特异性两亲性疫苗：1期AMPLIFY-201试验。《自然医学》30531-542（2024）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Haldar, S. D. et al. Abstract CT036: safety and immunogenicity of a first-in-human mutant KRAS long peptide vaccine combined with ipilimumab/nivolumab in resected pancreatic cancer: preliminary analysis from a phase I study. Cancer Res. 83 (Suppl. 8), CT036–CT036 (2023).Article

Haldar，S.D.等人摘要CT036：首次人类突变KRAS长肽疫苗联合ipilimumab/nivolumab在切除的胰腺癌中的安全性和免疫原性：I期研究的初步分析。癌症研究83（补充8），CT036–CT036（2023）。文章

Google Scholar

谷歌学者

Download referencesAuthor informationAuthors and AffiliationsDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USASaurav D. Haldar & Nilofer S. AzadAuthorsSaurav D. HaldarView author publicationsYou can also search for this author in

下载参考文献作者信息作者和附属机构约翰·霍普金斯大学医学院肿瘤学系，马里兰州巴尔的摩，USASaurav D.Haldar＆Nilofer S.AzadAuthorsSaurav D.HaldarView作者出版物您也可以在

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N.S.A. reports clinical research funding and consultant/advisory fees from Revolution Medicines, Mirati Therapeutics and Bristol Myers Squibb. S.D.H. declares no competing interests.

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Supplementary informationSupplementary informationRights and permissionsReprints and permissionsAbout this articleCite this articleHaldar, S.D., Azad, N.S. Unlocking the promise of RAS inhibition in pancreatic cancer.

补充信息补充信息权利和许可打印和许可本文引用本文Haldar，S.D.，Azad，N.S。解锁胰腺癌中RAS抑制的承诺。

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