Corcoran, R. B. et al. EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Nature 2, 227–235 (2012).
Prahallad, A. et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483, 100–103 (2012).
Kopetz, S. et al. Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial. Nat. Med. 30, 3261–3271 (2024).
Yi, Q. et al. Spectrum of BRAF aberrations and its potential clinical implications insights from integrative pan-cancer analysis. Front. Bioeng. Biotechnol. 14, 806851 (2022).
Kopetz, S. et al. Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J. Clin. Oncol. 33, 4032–4038 (2015).
Tabernero, J. et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J. Clin. Oncol. 39, 273–284 (2021).
Corcoran, R. B. et al. Combined BRAF, EGFR, and MEK inhibition in patients with BRAFV600E-mutant colorectal cancer. Cancer Discov. 8, 428–443 (2018).
Brennan, C. M. & Steitz, J. A. HuR and mRNA stability. Cell. Mol. Life Sci. 58, 266–277 (2001).
Mukherjee, N. et al. Integrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability. Mol. Cell 43, 327–339 (2011).
Wu, M., Tong, C. W. S., Yan, W., To, K. K. W. & Cho, W. C. S. The RNA binding protein HuR: a promising drug target for anticancer therapy. Curr. Cancer Drug Target. 19, 382–399 (2019).
Lachiondo-Ortega, S. et al. Hu antigen R (HuR) protein structure, function and regulation in hepatobiliary tumors. Cancers 14, 2666 (2022).
Kotta-Loizou, I., Giaginis, C. & Theocharis, S. Clinical significance of HuR expression in human malignancy. Med. Oncol. 31, 161 (2014).
Levy, N. S., Chung, S., Furneaux, H. & Levy, A. P. Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J. Biol. Chem. 273, 6417–6423 (1998).
Kurosu, T. et al. HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium. Br. J. Cancer 104, 819–829 (2011).
Finan, J. M., Sutton, T. L., Dixon, D. A. & Brody, J. R. Targeting the RNA-binding protein HuR in cancer. Cancer Res. 83, 3507–3516 (2023).
Lang, M. et al. HuR small-molecule inhibitor elicits differential effects in adenomatosis polyposis and colorectal carcinogenesis. Cancer Res. 77, 2424–2438 (2017).
Jimbo, M. et al. Targeting the mRNA-binding protein HuR impairs malignant characteristics of pancreatic ductal adenocarcinoma cells. Oncotarget 6, 27312–27331 (2015).
Chand, S. N. et al. Posttranscriptional regulation of PARG mRNA by HuR facilitates DNA repair and resistance to PARP inhibitors. Cancer Res. 77, 5011–5025 (2017).
Danilin, S. et al. Role of the RNA-binding protein HuR in human renal cell carcinoma. Carcinogenesis 31, 1018–1026 (2010).
Huang, Y.-H. et al. Delivery of therapeutics targeting the mRNA-binding protein HuR using 3DNA nanocarriers suppresses ovarian tumor growth. Cancer Res. 76, 1549–1559 (2016).
Yuan, Z., Sanders, A. J., Lin Ye, Y. W. & Jiang, W. G. Knockdown of human antigen R reduces the growth and invasion of breast cancer cells in vitro and affects expression of cyclin D1 and MMP-9. Oncol. Rep. 26, 237–245 (2011).
Zhang, Z., Huang, A., Zhang, A. & Zhou, C. HuR promotes breast cancer cell proliferation and survival via binding to CDK3 mRNA. Biomed. Pharmacother. 91, 788–795 (2017).
Papatheofani, V. et al. HuR protein in hepatocellular carcinoma: implications in development, prognosis and treatment. Biomedicines 9, 119 (2021).
Zhang, Y., Yang, L., Ling, C. & Heng, W. HuR facilitates cancer stemness of lung cancer cells via regulating miR-873/CDK3 and miR-125a-3p/CDK3 axis. Biotechnol. Lett. 40, 623–631 (2018).
Palomo-Irigoyen, M. et al. HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. J. Clin. Invest. 130, 3848–3864 (2020).
Schultz, C. W., Preet, R., Dhir, T., Dixon, D. A. & Brody, J. R. Understanding and targeting the disease-related RNA binding protein human antigen R (HuR). WIREs RNA 11, e1581 (2020).
Krönke, J. et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science 343, 301–305 (2014).
Wu, W. et al. Overcoming IMiD resistance in T-cell lymphomas through potent degradation of ZFP91 and IKZF1. Blood 139, 2024–2037 (2022).
Renneville, A. et al. Avadomide induces degradation of ZMYM2 fusion oncoproteins in hematologic malignancies. Blood Cancer Discov. 2, 250–265 (2021).
Matyskiela, M. E. et al. SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate. Nat. Chem. Biol. 14, 981–987 (2018).
Bonazzi, S. et al. Discovery and characterization of a selective IKZF2 glue degrader for cancer immunotherapy. Cell Chem. Biol. 30, 235–247.e12 (2023).
Ting, P. Y. et al. A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction. Science 385, 91–99 (2024).
Krönke, J. et al. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature 523, 183–188 (2015).
Matyskiela, M. E. et al. A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase. Nature 535, 252–257 (2016).
Matyskiela, M. E. et al. Crystal structure of the SALL4–pomalidomide–cereblon–DDB1 complex. Nat. Struct. Mol. Biol. 27, 319–322 (2020).
Fischer, E. S. et al. Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512, 49–53 (2014).
Petzold, G., Fischer, E. S. & Thomä, N. H. Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase. Nature 532, 127–130 (2016).
Akdel, M. et al. A structural biology community assessment of AlphaFold2 applications. Nat. Struct. Mol. Biol. 29, 1056–1067 (2022).
Dai, W., Zhang, G. & Makeyev, E. V. RNA-binding protein HuR autoregulates its expression by promoting alternative polyadenylation site usage. Nucleic Acids Res. 40, 787–800 (2012).
Sievers, Q. L. et al. Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN. Science 362, eaat0572 (2018).
Fink, E. C. et al. Crbn I391V is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice. Blood 132, 1535–1544 (2018).
Watson, E. R. et al. Molecular glue CELMoD compounds are regulators of cereblon conformation. Science 378, 549–553 (2022).
Abascal, F. et al. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583, 699–710 (2020).
Marranci, A. et al. The landscape of BRAF transcript and protein variants in human cancer. Mol. Cancer 16, 85 (2017).
Chang, S.-H. et al. Antagonistic function of the RNA-binding protein HuR and miR-200b in post-transcriptional regulation of vascular endothelial growth factor-A expression and angiogenesis. J. Biol. Chem. 288, 4908–4921 (2013).
Benson, A. B. et al. Colon Cancer, version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J. Natl Comp. Cancer Netw. 22, e240029 (2024).
Kopetz, S. et al. Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nat. Med. 31, 901–908 (2025).
Wang, A. et al. Long noncoding RNA EGFR-AS1 promotes cell growth and metastasis via affecting HuR mediated mRNA stability of EGFR in renal cancer. Cell Death Dis. 10, 154 (2019).
Kassabri, L. & Benhamou, R. I. Druglike molecular degraders of the oncogenic RNA-binding protein HuR. JACS Au 5, 3879–3891 (2025).
Fletcher, A. et al. A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation. Nat. Commun. 14, 7093 (2023).
Benoit, R. M. et al. The X-ray crystal structure of the first RNA recognition motif and site-directed mutagenesis suggest a possible HuR redox sensing mechanism. J. Mol. Biol. 397, 1231–1244 (2010).
