Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A. & Shokat, Ok. M. Ok-Ras(G12C) inhibitors allosterically management GTP affinity and effector interactions. Nature 503, 548–551 (2013).
Google Scholar
Canon, J. et al. The medical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature 575, 217–223 (2019).
Google Scholar
Hallin, J. et al. The KRAS(G12C) inhibitor MRTX849 offers perception towards therapeutic susceptibility of KRAS-mutant cancers in mouse fashions and sufferers. Most cancers Discov. 10, 54–71 (2020).
Google Scholar
Middleton, G. et al. The Nationwide Lung Matrix Trial of customized remedy in lung most cancers. Nature 583, 807–812 (2020).
Google Scholar
Zehir, A. et al. Mutational panorama of metastatic most cancers revealed from potential medical sequencing of 10,000 sufferers. Nat. Med. 23, 703–713 (2017).
Google Scholar
Ramalingam, S. S. et al. General survival with osimertinib in untreated, EGFR-mutated superior NSCLC. N. Engl. J. Med. 382, 41–50 (2020).
Google Scholar
Diederichs, S. et al. The darkish matter of the most cancers genome: aberrations in regulatory parts, untranslated areas, splice websites, non-coding RNA and synonymous mutations. EMBO Mol. Med. 8, 442–457 (2016).
Google Scholar
Group, P. T. C. et al. Genomic foundation for RNA alterations in most cancers. Nature 578, 129–136 (2020).
Google Scholar
Consortium, A. P. G. AACR venture GENIE: powering precision drugs by means of a global consortium. Most cancers Discov. 7, 818–831 (2017).
Janne, P. A. et al. Selumetinib plus docetaxel in contrast with docetaxel alone and progression-free survival in sufferers with KRAS-mutant superior non-small cell lung most cancers: the SELECT-1 randomized medical trial. JAMA 317, 1844–1853 (2017).
Google Scholar
Kitai, H. et al. Epithelial-to-mesenchymal transition defines suggestions activation of receptor tyrosine kinase signaling induced by MEK inhibition in KRAS-mutant lung most cancers. Most cancers Discov. 6, 754–769 (2016).
Google Scholar
Kruspig, B. et al. The ERBB community facilitates KRAS-driven lung tumorigenesis. Sci. Transl. Med. 10, eaao2565 (2018).
Google Scholar
Moll, H. P. et al. Afatinib restrains Ok-RAS-driven lung tumorigenesis. Sci. Transl. Med. 10, eaao2301 (2018).
Google Scholar
LaMarche, M. J. et al. Identification of TNO155, an allosteric SHP2 inhibitor for the therapy of most cancers. J. Med. Chem. 63, 13578–13594 (2020).
Google Scholar
Hong, D. S. et al. KRAS(G12C) inhibition with sotorasib in superior stable tumors. N. Engl. J. Med. 383, 1207–1217 (2020).
Google Scholar
Hunter, J. C. et al. Biochemical and structural evaluation of frequent cancer-associated KRAS mutations. Mol. Most cancers Res. 13, 1325–1335 (2015).
Google Scholar
Zhou, Z. W. et al. KRASQ61H preferentially alerts by means of MAPK in a RAF dimer-dependent method in non-small cell lung most cancers. Most cancers Res. 80, 3719–3731 (2020).
Google Scholar
Oxnard, G. R. et al. Evaluation of resistance mechanisms and medical implications in sufferers with EGFR T790M-positive lung most cancers and bought resistance to osimertinib. JAMA Oncol. 4, 1527–1534 (2018).
Google Scholar
Ramalingam, S. S. et al. Mechanisms of acquired resistance to first-line osimertinib: preliminary information from the part III FLAURA examine. Ann. Oncol 29, VIII740 (2018).
Reinert, T. et al. Evaluation of plasma cell-free DNA by ultradeep sequencing in sufferers with levels I to III colorectal most cancers. JAMA Oncol. 5, 1124–1131 (2019).
Google Scholar
Chabon, J. J. et al. Integrating genomic options for non-invasive early lung most cancers detection. Nature 580, 245–251 (2020).
Google Scholar
Amendola, C. R. et al. KRAS4A immediately regulates hexokinase 1. Nature 576, 482–486 (2019).
Google Scholar
Cartegni, L., Chew, S. L. & Krainer, A. R. Listening to silence and understanding nonsense: exonic mutations that have an effect on splicing. Nat. Rev. Genet. 3, 285–298 (2002).
Google Scholar
Desmet, F. O. et al. Human Splicing Finder: a web based bioinformatics instrument to foretell splicing alerts. Nucleic Acids Res. 37, e67 (2009).
Google Scholar
McVety, S., Li, L., Gordon, P. H., Chong, G. & Foulkes, W. D. Disruption of an exon splicing enhancer in exon 3 of MLH1 is the reason for HNPCC in a Quebec household. J. Med. Genet. 43, 153–156 (2006).
Google Scholar
Khvorova, A. & Watts, J. Ok. The chemical evolution of oligonucleotide therapies of medical utility. Nat. Biotechnol. 35, 238–248 (2017).
Google Scholar
Kim, J. et al. Affected person-customized oligonucleotide remedy for a uncommon genetic illness. N. Engl. J. Med. 381, 1644–1652 (2019).
Google Scholar
Janes, M. R. et al. Focusing on KRAS mutant cancers with a covalent G12C-specific inhibitor. Cell 172, 578–589.e517 (2018).
Google Scholar
Brant, R. et al. Clinically viable gene expression assays with potential for predicting profit from MEK inhibitors. Clin. Most cancers Res. 23, 1471–1480 (2017).
Google Scholar
Chang, M. T. et al. Figuring out recurrent mutations in most cancers reveals widespread lineage range and mutational specificity. Nat. Biotechnol. 34, 155–163 (2016).
Google Scholar
Zammarchi, F. et al. Antitumorigenic potential of STAT3 various splicing modulation. Proc. Natl Acad. Sci. USA 108, 17779–17784 (2011).
Google Scholar
Ross, S. J. et al. Focusing on KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS. Sci. Transl. Med. 9, eaal5253 (2017).
Google Scholar
Amodio, V. et al. EGFR blockade reverts resistance to KRASG12C inhibition in colorectal most cancers. Most cancers Discov. 10, 1129–1139 (2020).
Google Scholar
Klein, A. F. et al. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice. J. Clin. Make investments. 129, 4739–4744 (2019).
Google Scholar
Boisguerin, P. et al. Supply of therapeutic oligonucleotides with cell penetrating peptides. Adv. Drug Deliv. Rev. 87, 52–67 (2015).
Google Scholar
Imbert, M., Dias-Florencio, G. & Goyenvalle, A. Viral vector-mediated antisense remedy for genetic ailments. Genes 8, 51 (2017).
Google Scholar
Sharma, Y. et al. A pan-cancer evaluation of synonymous mutations. Nat. Commun. 10, 2569 (2019).
Google Scholar
Cartegni, L., Wang, J., Zhu, Z., Zhang, M. Q. & Krainer, A. R. ESEfinder: An online useful resource to establish exonic splicing enhancers. Nucleic Acids Res. 31, 3568–3571 (2003).
Google Scholar
Smith, P. J. et al. An elevated specificity rating matrix for the prediction of SF2/ASF-specific exonic splicing enhancers. Hum. Mol. Genet. 15, 2490–2508 (2006).
Google Scholar
Fairbrother, W. G. et al. RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons. Nucleic Acids Res. 32, W187–W190 (2004).
Google Scholar
Zhang, X. H. & Chasin, L. A. Computational definition of sequence motifs governing constitutive exon splicing. Genes Dev. 18, 1241–1250 (2004).
Google Scholar
Hori, S.-i et al. Ca2+ enrichment in tradition medium potentiates impact of oligonucleotides. Nucleic Acids Res. 43, e128 (2015).
Google Scholar
Garcia, E. P. et al. Validation of OncoPanel: a focused next-generation sequencing assay for the detection of somatic variants in most cancers. Arch. Pathol. Lab. Med. 141, 751–758 (2017).
Google Scholar
Odegaard, J. I. et al. Validation of a plasma-based complete most cancers genotyping assay using orthogonal tissue- and plasma-based methodologies. Clin. Most cancers Res. 24, 3539–3549 (2018).
Google Scholar