The KRAS-G12C inhibitor: activity and resistance - Nature
2021年9月1日 · In 2021, the U.S. Food and Drug Administration (FDA) accelerated the approval of sotorasib as the first KRAS-G12C blocking drug for the treatment of adult patients with NSCLC.
KRAS G12C Inhibitors: New Drugs, A New Hope - Journal of …
The ongoing research into new KRAS G12C inhibitors and their mechanisms offers hope for overcoming these barriers and achieving more durable responses.
KRAS mutation: from undruggable to druggable in cancer
2021年11月15日 · Recently, there has been light on the horizon for one specific mutation, KRAS (G12C). With the discovery of a new allosteric site of KRAS (G12C), several irreversible covalently binding...
The path to the clinic: a comprehensive review on direct KRAS G12C ...
Analyzing amino acid-specific KRAS mutations in the three cancer types responsible for most KRAS mutations, the most common KRAS mutation in NSCLC adenocarcinoma subtype is KRAS G12C (glycine to cysteine) (33.4%), while the most common KRAS mutation in colon and rectal adenocarcinoma and pancreatic ductal adenocarcinoma is KRAS G12D (glycine to ...
Sotorasib for Lung Cancers with KRAS p.G12C Mutation
2021年6月4日 · Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of...
Targeting KRAS in cancer - Nature Medicine
2024年4月18日 · The first successes occurred with allele-specific targeting of KRAS p.Gly12Cys (G12C) in non-small cell lung cancer, resulting in regulatory approval of two agents—sotorasib and adagrasib.
Targeting KRAS(G12C): From Inhibitory Mechanism to Modulation of ...
Recent advances in medicinal chemistry have established inhibitors targeting KRAS (G12C), a mutation found in ∼13% of lung adenocarcinomas and, at a lower frequency, in other cancers.
KRAS G12C mutation: from undruggable target to potentially …
With the expansion of these inhibitors to other solid malignancies and the reported promising outcomes (20,21), KRAS G12C mutation has the potential to become the next agnostic cancer biomarker in the era of precision oncology.
KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and …
2023年10月1日 · KRAS G12C is the most common KRAS variant at ∼13% of NSCLC cases overall. Approved RAS GTPase inhibitors transform KRAS G12C into a predictive biomarker. Real-world studies show significant geographic variation in KRAS G12C prevalence.
Landscape of KRASG12C, Associated Genomic Alterations, and ...
2022年3月23日 · KRAS G12C was most prevalent in patients with non–small-cell lung cancer, appendiceal, colorectal, tumor of unknown origin, small bowel, and pancreatic cancers. KRAS G12C tumors were genomically distinct from KRAS non-G12C tumors, including variations in STK11, KEAP1, and other gene frequencies.
Prognostic Role of KRAS G12C Mutation in Non-Small Cell Lung …
KRAS G12C mutation (mKRAS G12C) is the most frequent KRAS point mutation in non-small cell lung cancer (NSCLC) and has been proven to be a predictive biomarker for direct KRAS G12C inhibitors in advanced solid cancers.
Cracking KRAS G12C across all solid tumors: the new kid on
2023年6月30日 · Landscape of KRAS G12C, associated genomic alterations, and interrelation with immuno-oncology biomarkers in KRAS-mutated cancers
KRAS inhibitors: resistance drivers and combinatorial strategies
Similarly, KRAS G12C amplifications have been identified as significant resistance drivers to KRAS G12C inhibitor therapy in both CRC and NSCLC [81,87,88]. KRAS G12C amplification leads to an increased amount of KRAS protein, which is initially GTP loaded due to the 10:1 GTP:GDP ratio within the cell .
Outcomes following KRASG12C inhibitor treatment in patients …
2024年2月1日 · This study provided a comprehensive understanding of the efficacy and safety of KRAS G12C inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRAS G12C inhibitors.
KRAS
2022年6月21日 · We find that upstream feedback activation of wild-type RAS, as opposed to a shift in KRAS G12C to its active guanosine triphosphate (GTP)-bound state, is sufficient to drive RAS-MAPK reactivation in a KRAS G12C -independent manner.
KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors
2020年9月20日 · We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. Patients received sotorasib orally once daily. The primary end point was...
Acquired Resistance to KRAS G12C Inhibition in Cancer - The New …
2021年6月23日 · Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS G12C)....
Updated Data from the Phase 1/2 Study of Olomorasib in KRAS G12C …
Updated Data from the Phase 1/2 Study of Olomorasib in KRAS G12C-Mutant ...
Discovery of novel tetracyclic quinazolines as multi-KRAS
1 天前 · Recently, a variety of KRAS inhibitors have been reported using SIIPs including the introduction of various functional groups such as aminopyridine, 27 aminobenzothiazole, 28 and aminobenzothiophene 29 into A-part or the cyclization of the core and B-part. 30 In particular, the derivation of a benzothiophene compound as a KRAS G12C inhibitor ...
Verastem Oncology Provides a Clinical Update for RAMP 203 Trial …
2024年12月18日 · The KRAS G12C inhibitor prior-treated Stage I Part B cohort is still enrolling patients and is anticipated to complete enrollment in early 2025. Patients in both cohorts continue to be followed ...
What is KRAS G12C? | LUMAKRAS® (sotorasib)
Learn why understanding the KRAS G12C mutation is an important part of your non-small cell lung cancer (NSCLC) treatment plan. See full Prescribing & Safety Info.
How to manage KRAS G12C-mutated advanced non-small-cell …
2022年7月4日 · Here, we review the current treatment landscape for patients with advanced NSCLCs harbouring a KRAS G12C mutation, including PD- (L) 1-based therapies and direct KRAS inhibitors as well as sequential treatment options.
ORR 49.1%！首个上市国产抑制剂破局 KRAS G12C 突变 NSCLC 治 …
2024年12月20日 · KRAS 作为常见的致癌驱动突变，因其独特的空间结构和生化特征，长期以来被认为是「不可成药」的靶点。但近年来，两款 KRAS G12C 抑制剂 Sotorasib 和 ...
4款已上市KRAS G12C抑制剂：索托拉西布、阿达格拉西布、氟泽 …
2024年12月19日 · kras g12c突变导致kras蛋白持续激活，刺激细胞增殖和存活，促进肿瘤发展。 这一突变在多种恶性肿瘤中普遍存在，包括胰腺癌、结直肠癌和肺癌，尤其在非小细胞肺癌中的突变比率高达21.6%。
KRAS基因G12C突变的病友看过来，抗癌新药三期临床招募进行中…
2 天之前 · 晚期肺癌的KRAS基因有多种突变形式，其中G12C突变位点最近比较受关注。针对这个基因突变位点最近出现了很多的靶向药，很多携带G12C突变的病友 ...
Sotorasib 修饰的 KRAS G12C-MHC I 复合物的治疗靶向和结构表 …
阐明与半抗原化 KRAS G12C 肽-MHC I 复合物结合的 P1B7 的 3.1 Å 冷冻电镜结构证实，Sotorasib 修饰的 KRAS G12C 肽通过经典结合姿势呈现，并表明 P1B7 以 T 细胞受体样方式结合复合物。总之，这些发现证明了用放射性配体
KRAS G12C inhibitor combination therapies: current evidence and ...
Multiple combinations of KRAS G12C inhibitors with other targeted therapies, such as RTK, SHP2, and MEK inhibitors, have been investigated in clinical trials to overcome the resistance. They have demonstrated promising efficacy especially by combining KRAS G12C and EGFR inhibitors for KRAS G12C-mutated colorectal cancer.
【一帮医】KRAS G12C突变患者，国研和进口靶向药：氟泽雷塞、 …
1 天前 · 然而在其后的40年里，由于kras独特的蛋白形状，被医学界认定为“不可成药”，众多病友在绝望的等待中离世。kras g12c突变是kras基因的一种常见突变形式，该突变导致kras蛋白持续处于活性状态，进而促进肿瘤细胞的生长和扩散，曾被视为“不可战胜”的敌人。
国内首个获批KRAS G12C抑制剂氟泽雷塞片（达伯特）,开启KRAS …
4 天之前 · 这些突变包括多种位点的变异，其中g12c、g12d和g12r突变最为常见。 kras g12突变占所有kras突变的44%，此外还有g12a、g12s、g12v、g13d等其他类型的突变。由于kras蛋白的结构特点和其与gdp或gtp的高结合力，使
肺癌精准靶向治疗时代，KRAS G12C突变患者有药可依，格索雷塞 …
2 天之前 · 随着肺癌精准靶向治疗的深入研究，kras蛋白的结构逐渐被揭开，特别是switch ii口袋的发现，为kras g12c的靶向治疗带来了转机。 这个独特的口袋允许G12C抑制剂优先结合在KRAS蛋白的GDP结合构象中，通过阻断GTP的交换，抑制信号级联的激活，从而有效阻止肿瘤细胞的 ...