CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?
KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?
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KRAS突变是癌症中最常见的突变之一。在数十年来被认为不可成药之后，KRAS G12C特异性抑制剂表明，可以针对这一臭名昭著的靶点开发小分子抑制剂。与此同时，仍然没有能够靶向KRAS G12D的药物，而KRAS G12D是最常见的KRAS突变，存在于大多数KRAS突变的胰腺肿瘤中。尽管如此，随着几种能够结合并抑制KRAS G12D的化合物的开发，G12D领域目前正在取得重大进展，其中最引人注目的是MRTX1133。该领域令人振奋的进展还包括一种免疫治疗方法，即利用过继性T细胞转移来特异性靶向胰腺癌中的G12D。在这篇小型综述中，我们讨论了KRAS G12D靶向治疗的最新进展以及各种方法进一步临床开发的潜力。
KRAS mutations are among the most commonly occurring mutations in cancer. After being deemed undruggable for decades, KRAS G12C specific inhibitors showed that small molecule inhibitors can be developed against this notorious target. At the same time, there is still no agent that could target KRAS G12D which is the most common KRAS mutation and is found in the majority of KRAS-mutated pancreatic tumors.
Nevertheless, significant progress is now being made in the G12D space with the development of several compounds that can bind to and inhibit KRAS G12D, most notably MRTX1133. Exciting advances in this field also include an immunotherapeutic approach that uses adoptive T-cell transfer to specifically target G12D in pancreatic cancer. In this mini-review, we discuss recent advances in KRAS G12D targeting and the potential for further clinical development of the various approaches.
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