RET Inhibitors in Non-Small-Cell Lung Cancer.
RET Inhibitors in Non-Small-Cell Lung Cancer.
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DOI：
10.3390/cancers13174415
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发表时间：
2021-09-01
期刊：
影响因子：
5.2
通讯作者：
Morabito A
中科院分区：
文献类型：
--
作者：
Cascetta P;Sforza V;Manzo A;Carillio G;Palumbo G;Esposito G;Montanino A;Costanzo R;Sandomenico C;De Cecio R;Piccirillo MC;La Manna C;Totaro G;Muto P;Picone C;Bianco R;Normanno N;Morabito A
非小细胞肺癌（NSCLC）仍然是世界范围内的一个重要死亡原因，尽管迄今为止取得了重大进展。在非小细胞肺癌中已经发现了多种分子改变，这导致了基于靶标的药物的发展，这些药物已经显示出显著的临床益处。在转染期间重排（RET）融合最近成为一个新的潜在靶点，许多非选择性和选择性RET抑制剂已经在RET阳性的NSCLC中进行了测试。在本文中，我们分析和总结了RET功能的特点及其在非小细胞肺癌中的改变。然后，我们介绍了RET抑制剂治疗非小细胞肺癌的最新进展，讨论了RET阳性（RET+）非小细胞肺癌患者正在进行的试验和未来的前景。在1-2%的非小细胞肺癌（NSCLC）患者中观察到RET重排，并导致下游通路的组成性激活，通常意味着细胞增殖、生长、分化和存活。在非小细胞肺癌患者中，RET重排与不吸烟史、初始诊断时较高的脑转移率和低免疫浸润有关。传统上，RET融合被认为与其他致癌驱动因素相互排斥，尽管已经观察到与EGFR突变和MET扩增共同发生。Cabozantinib， vandetanib和lenvatinib是首批在ret重排NSCLC患者中测试的多激酶抑制剂，结果对比明显。最近，两种选择性RET抑制剂selpercatinib和pralsetinib显示出更高的有效率和良好的耐受性，并且基于II期研究结果，它们被批准用于治疗转移性RET融合阳性NSCLC患者。两项正在进行的III期临床试验目前正在比较selpercatinib或pralsetinib与标准一线治疗，并将明确确定其对ret阳性NSCLC患者的疗效。
Non-small cell lung cancer (NSCLC) remains a significant cause of death worldwide, despite the significant progresses to date. Multiple molecular alterations have been identified in NSCLC, leading to the development of target-based agents that have shown significant clinical benefits. Rearranged during Transfection (RET) fusions have recently emerged as a new potential target and a number of non-selective and selective RET inhibitors have been tested in RET positive NSCLC. In this review we analyse and summarise the characteristics of RET functions and its alterations in NSCLC. We then present the state of the art RET inhibitors in the treatment of NSCLC, discussing the ongoing trials and the future perspectives for RET positive (RET+) NSCLC patients. RET rearrangements are observed in 1–2% of non-small-cell lung cancer (NSCLC) patients and result in the constitutive activation of downstream pathways normally implied in cell proliferation, growth, differentiation and survival. In NSCLC patients, RET rearrangements have been associated with a history of non-smoking, a higher rate of brain metastasis at initial diagnosis and a low immune infiltrate. Traditionally, RET fusions are considered mutually exclusive with other oncogenic drivers, even though a co-occurrence with EGFR mutations and MET amplifications has been observed. Cabozantinib, vandetanib and lenvatinib are the first multi-kinase inhibitors tested in RET-rearranged NSCLC patients with contrasting results. More recently, two selective RET inhibitors, selpercatinib and pralsetinib, demonstrated higher efficacy rates and good tolerability and they were approved for the treatment of patients with metastatic RET fusion-positive NSCLC on the bases of the results of phase II studies. Two ongoing phase III clinical trials are currently comparing selpercatinib or pralsetinib to standard first line treatments and will definitively establish their efficacy in RET-positive NSCLC patients.
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DOI：
10.1056/nejmoa2005653
发表时间：
2020-08-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Drilon A;Oxnard GR;Tan DSW;Loong HHF;Johnson M;Gainor J;McCoach CE;Gautschi O;Besse B;Cho BC;Peled N;Weiss J;Kim YJ;Ohe Y;Nishio M;Park K;Patel J;Seto T;Sakamoto T;Rosen E;Shah MH;Barlesi F;Cassier PA;Bazhenova L;De Braud F;Garralda E;Velcheti V;Satouchi M;Ohashi K;Pennell NA;Reckamp KL;Dy GK;Wolf J;Solomon B;Falchook G;Ebata K;Nguyen M;Nair B;Zhu EY;Yang L;Huang X;Olek E;Rothenberg SM;Goto K;Subbiah V
通讯作者：
Subbiah V
DOI：
10.1016/s1470-2045(10)70132-7
发表时间：
2010-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Herbst RS;Sun Y;Eberhardt WE;Germonpré P;Saijo N;Zhou C;Wang J;Li L;Kabbinavar F;Ichinose Y;Qin S;Zhang L;Biesma B;Heymach JV;Langmuir P;Kennedy SJ;Tada H;Johnson BE
通讯作者：
Johnson BE
影响因子：
51.1
作者：
Drilon, Alexander;Rekhtman, Natasha;Arcila, Maria;Wang, Lu;Ni, Andy;Albano, Melanie;Van Voorthuysen, Martine;Somwar, Romel;Smith, Roger S.;Montecalvo, Joseph;Plodkowski, Andrew;Ginsberg, Michelle S.;Riely, Gregory J.;Rudin, Charles M.;Ladanyi, Marc;Kris, Mark G.
通讯作者：
Kris, Mark G.
影响因子：
28.2
作者：
Drilon A;Wang L;Hasanovic A;Suehara Y;Lipson D;Stephens P;Ross J;Miller V;Ginsberg M;Zakowski MF;Kris MG;Ladanyi M;Rizvi N
通讯作者：
Rizvi N
影响因子：
11.5
作者：
Kato, Shumei;Subbiah, Vivek;Kurzrock, Razelle
通讯作者：
Kurzrock, Razelle