A Next-Generation BRAF Inhibitor Overcomes Resistance to BRAF Inhibition in Patients with BRAF-Mutant Cancers Using Pharmacokinetics-Informed Dose Escalation

新一代 BRAF 抑制剂利用药代动力学知情剂量递增克服了 BRAF 突变型癌症患者对 BRAF 抑制的耐药性

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作者：Rona Yaeger, Meredith A McKean, Rizwan Haq, J Thaddeus Beck, Matthew H Taylor, Jonathan E Cohen, Daniel W Bowles, Shirish M Gadgeel, Catalin Mihalcioiu, Kyriakos P Papadopoulos, Eli L Diamond, Keren B Sturtz, Gang Feng, Stefanie K Drescher, Micaela B Reddy, Bhaswati Sengupta, Arnab K Maity, Suzy A B

期刊：

Cancer Discovery

影响因子：

29.700

时间：

2024

起止号：

2024 Sep 4;14(9):1599-1611.

doi：

10.1158/2159-8290.CD-24-0024

研究方向：

肿瘤

Significance

PF-07799933 treatment was associated with antitumor activity against BRAFV600- and non-V600-mutant cancers preclinically and in treatment-refractory patients, and PF-07799933 could be safely combined with a MEK inhibitor. The novel, rapid pharmacokinetics (PK)-informed dose escalation design provides a new paradigm for accelerating the testing of next-generation targeted therapies early in clinical development.

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