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Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future

靶向 KRAS 突变型非小细胞肺癌: 过去、现在和未来

  • 影响因子:4.32
  • DOI:10.3390/ijms21124325
  • 作者列表:"Iris Z. Uras","Herwig P. Moll","Emilio Casanova
  • 发表时间:2020-06-18
Abstract

Lung cancer is the most frequent cancer with an aggressive clinical course and high mortality rates. Most cases are diagnosed at advanced stages when treatment options are limited and the efficacy of chemotherapy is poor. The disease has a complex and heterogeneous background with non-small-cell lung cancer (NSCLC) accounting for 85% of patients and lung adenocarcinoma being the most common histological subtype. Almost 30% of adenocarcinomas of the lung are driven by an activating <i>Kirsten rat sarcoma viral oncogene homolog</i> (<i>KRAS</i>) mutation. The ability to inhibit the oncogenic <i>KRAS</i> has been the holy grail of cancer research and the search for inhibitors is immensely ongoing as <i>KRAS</i>-mutated tumors are among the most aggressive and refractory to treatment. Therapeutic strategies tailored for <i>KRAS<sup>+</sup></i> NSCLC rely on the blockage of KRAS functional output, cellular dependencies, metabolic features, KRAS membrane associations, direct targeting of <i>KRAS</i> and immunotherapy. In this review, we provide an update on the most recent advances in anti-KRAS therapy for lung tumors with mechanistic insights into biological diversity and potential clinical implications.

摘要

肺癌是最常见的癌症,具有积极的临床过程和高死亡率。大多数病例在治疗选择有限和化疗疗效差的晚期诊断。该病具有复杂的异质性背景,其中非小细胞肺癌 (NSCLC) 占 85%,肺腺癌是最常见的组织学亚型。几乎 30% 的肺腺癌是由激活的 <i>Kirsten 大鼠肉瘤病毒癌基因同源物 </i> (<i>KRAS</i>) 突变驱动的。抑制致癌 <i>KRAS</i> 的能力一直是癌症研究的圣杯,寻找抑制剂的工作正在进行中,如 <i>KRAS</i>-突变的肿瘤是最具侵袭性和难治性的治疗之一。为 <i>KRAS<sup>+</sup></i> NSCLC 量身定制的治疗策略依赖于 KRAS 功能输出、细胞依赖性、代谢特征、 KRAS 膜关联的阻断,直接靶向 <i>KRAS</i> 和免疫治疗。在这篇综述中,我们提供了抗 KRAS 治疗肺部肿瘤的最新进展,对生物多样性和潜在临床意义的机制见解。

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作者列表:["Esme H","Can A","Şehitogullari A"]

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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.

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影响因子:8.44
发表时间:2020-02-01
DOI:10.1016/j.annonc.2019.10.022
作者列表:["Mazieres J","Cropet C","Montané L","Barlesi F","Souquet PJ","Quantin X","Dubos-Arvis C","Otto J","Favier L","Avrillon V","Cadranel J","Moro-Sibilot D","Monnet I","Westeel V","Le Treut J","Brain E","Trédaniel J","Jaffro M","Collot S","Ferretti GR","Tiffon C","Mahier-Ait Oukhatar C","Blay JY"]

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