Cited by 145Melanoma and MAPK PathwaysProtein Kinase Regulation and GTPase SignalingLung Cancer Treatments and Mutations

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Molecular Pathways and Mechanisms of BRAF in Cancer Therapy

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Poulikakos, Poulikos I., Sullivan, Ryan J., Yaeger, Rona·2022·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-21-2138PMC PMC9616966

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Abstract

With the identification of activating mutations in BRAF across a wide variety of malignancies, substantial effort was placed in designing safe and effective therapeutic strategies to target BRAF. These efforts have led to the development and regulatory approval of three BRAF inhibitors as well as five combinations of a BRAF inhibitor plus an additional agent(s) to manage cancer such as melanoma, non–small cell lung cancer, anaplastic thyroid cancer, and colorectal cancer. To date, each regimen is effective only in patients with tumors harboring BRAFV600 mutations and the duration of benefit is often short-lived. Further limitations preventing optimal management of BRAF-mutant malignancies are that treatments of non-V600 BRAF mutations have been less profound and combination therapy is likely necessary to overcome resistance mechanisms, but multi-drug regimens are often too toxic. With the emergence of a deeper understanding of how BRAF mutations signal through the RAS/MAPK pathway, newer RAF inhibitors are being developed that may be more effective and potentially safer and more rational combination therapies are being tested in the clinic. In this review, we identify the mechanics of RAF signaling through the RAS/MAPK pathway, present existing data on single-agent and combination RAF targeting efforts, describe emerging combinations, summarize the toxicity of the various agents in clinical testing, and speculate as to where the field may be headed.

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Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma
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Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy
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Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers
Peng, S.-B., Henry, J. R., Kaufman, M. D., Lu, W.-P., Smith, B. D., Vogeti, S., Rutkoski, T. J., Wise, S., Chun, L., Zhang, Y., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.08.002 · Cited by 303
c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma
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Pilot Trial of Combined BRAF and EGFR Inhibition in BRAF -Mutant Metastatic Colorectal Cancer Patients
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The Mammalian MAPK/ERK Pathway Exhibits Properties of a Negative Feedback Amplifier
Sturm, O. E., Orton, R. J., Grindlay, J., Birtwistle, M. R., Vyshemirsky, V., Gilbert, D., Muffy Calder, A., Pitt, A. R., Kholodenko, B. Ν., & Kölch, W. (2010) · Science Signaling · doi:10.1126/scisignal.2001212 · Cited by 248
Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients
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A Phase Ib Dose-Escalation Study of Encorafenib and Cetuximab with or without Alpelisib in Metastatic BRAF -Mutant Colorectal Cancer
van Geel, R. M. J. M., Tabernero, J., Elez, E., Bendell, J. C., Spreafico, A., Schuler, M., Yoshino, T., Delord, J.-P., Yamada, Y., Lolkema, M. P., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0795 · Cited by 232
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SHP2 drives adaptive resistance to ERK signaling inhibition in molecularly defined subsets of ERK-dependent tumors
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Chapter 1 Ras Signaling and Therapies
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Effects of Raf Dimerization and Its Inhibition on Normal and Disease-Associated Raf Signaling
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An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling
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Ras-Mediated Activation of the Raf Family KinasesPreprint
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RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling
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Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120
Chen, S.-H., Zhang, Y., Van Horn, R. D., Yin, T., Buchanan, S., Yadav, V., Mochalkin, I., Wong, S. S., Yue, Y. G., Huber, L., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0896 · Cited by 171
Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation
Thevakumaran, N., Lavoie, H., Critton, D., Tebben, A. J., Marinier, A., Sicheri, F., & Therrien, M. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2924 · Cited by 169
Mutant-selective degradation by BRAF-targeting PROTACs
Alabi, S., Jaime-Figueroa, S., Yao, Z., Gao, Y., Hines, J., Samarasinghe, K. T. G., Vogt, L., Rosen, N., & Crews, C. M. (2021) · Nature Communications · doi:10.1038/s41467-021-21159-7 · Cited by 152
ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma
Yen, I., Shanahan, F., Lee, J., Hong, Y. S., Shin, S. J., Moore, A. R., Sudhamsu, J., Chang, M. T., Bae, I., Dela Cruz, D., et al. (2021) · Nature · doi:10.1038/s41586-021-03515-1 · Cited by 138
Functional characterization of a PROTAC directed against BRAF mutant V600E
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Antitumor Activity of the Selective Pan-RAF Inhibitor TAK-632 in BRAF Inhibitor-Resistant Melanoma
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Continuous versus intermittent BRAF and MEK inhibition in patients with BRAF-mutated melanoma: a randomized phase 2 trial
Algazi, A. P., Othus, M. K. D., DAUD, A. I., Lo, R. S., Mehnert, J. M., Truong, T., Conry, R. M., Kendra, K. L., Doolittle, G. C., Clark, J. I., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1060-8 · Cited by 121
Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i
Dummer, R., Lebbé, C., Atkinson, V. G., Mandalà, M., Nathan, P., Arance, A. M., Richtig, E., Yamazaki, N., Robert, C., Schadendorf, D., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1082-2 · Cited by 120
Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors
Desai, J., Gan, H. K., Barrow, C., Jameson, M. B., Atkinson, V. G., Haydon, A. M., Millward, M., Begbie, S. D., Brown, M. P., Markman, B., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.19.02654 · Cited by 117
Complete regression of advanced pancreatic ductal adenocarcinomas upon combined inhibition of EGFR and C-RAF
Blasco, M. T., Navas, C., Martín-Serrano, G., Graña-Castro, O., Lechuga, C. G., Martín-Díaz, L., Djurec, M., Li, J., Morales-Cacho, L., Esteban-Burgos, L., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.03.002 · Cited by 115
Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses
Botton, T., Talevich, E., Mishra, V. K., Zhang, T., Shain, A. H., Berquet, C., Gagnon, A., Judson, R. L., Ballotti, R., Ribas, A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.009 · Cited by 113
Phase 2 results: Encorafenib (ENCO) and cetuximab (CETUX) with or without alpelisib (ALP) in patients with advanced BRAF-mutant colorectal cancer (BRAFm CRC).
Tabernero, J. M., van Geel, R. M. J. M., Guren, T. K., Yaeger, R. D., Spreafico, A., Faris, J. E., Yoshino, T., Yamada, Y., Kim, T. W., Bendell, J. C., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.3544 · Cited by 99
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Non-V600 BRAF mutations recurrently found in lung cancer predict sensitivity to the combination of Trametinib and Dabrafenib
Noeparast, A., Teugels, E., Giron, P., Verschelden, G., Brakeleer, S. D., Decoster, L., & Grève, J. D. (2016) · Oncotarget · doi:10.18632/oncotarget.11635 · Cited by 98
Mechanisms of Acquired Resistance to BRAF V600E Inhibition in Colon Cancers Converge on RAF Dimerization and Are Sensitive to Its Inhibition
Yaeger, R., Yao, Z., Hyman, D. M., Hechtman, J. F., Vakiani, E., Zhao, H., Su, W., Wang, L., Joelson, A., Cercek, A., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0768 · Cited by 94
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PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma
Ribas, A., Algazi, A. P., Ascierto, P. A., Butler, M. O., Chandra, S., Gordon, M. S., Hernandez-Aya, L. F., Lawrence, D. P., Lutzky, J., Miller, W. H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19810-w · Cited by 92
LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors
Monaco, K., Delach, S. M., Yuan, J., Mishina, Y. M., Fordjour, P., Labrot, E., McKay, D., Guo, R., Higgins, S., Wang, H. Q., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2563 · Cited by 91
Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131)
Johnson, D. B., Zhao, F., Noel, M. S., Riely, G. J., Mitchell, E. P., Wright, J. J., Chen, H. X., Gray, R. J., Li, S., McShane, L. M., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3443 · Cited by 90
BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF -Mutated Colorectal Cancers
Tang, Z., Yuan, X., Du, R., Cheung, S.-H., Zhang, G., Wei, J., Zhao, Y., Feng, Y., Peng, H., Zhang, Y., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0262 · Cited by 82
Genetic and Genomic Characterization of 462 Melanoma Patient-Derived Xenografts, Tumor Biopsies, and Cell Lines
Garman, B., Anastopoulos, I. N., Krepler, C., Brafford, P. A., Sproesser, K., Jiang, Y., Wubbenhorst, B. S., Amaravadi, R. K., Bennett, J., Beqiri, M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.052 · Cited by 79
Convergent Therapeutic Strategies to Overcome the Heterogeneity of Acquired Resistance in BRAF V600E Colorectal Cancer
Hazar-Rethinam, M. H., Kleyman, M., Han, G. C., Liu, D., Ahronian, L. G., Shahzade, H. A., Chen, L., Parikh, A. R., Allen, J. N., Clark, J. W., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1227 · Cited by 77
Pharmacological Induction of RAS-GTP Confers RAF Inhibitor Sensitivity in KRAS Mutant Tumors
Yen, I., Shanahan, F., Merchant, M. A., Orr, C., Hunsaker, T., Durk, M. R., La, H., Zhang, X., Martin, S. E., Lin, E., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.09.002 · Cited by 77
Dual MAPK Inhibition Is an Effective Therapeutic Strategy for a Subset of Class II BRAF Mutant Melanomas
Dankner, M., Lajoie, M., Moldoveanu, D., Nguyen, T.-T., Savage, P., Rajkumar, S., Huang, X., Lvova, M., Protopopov, A. I., Vuzman, D., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3384 · Cited by 76
RAF inhibitor LY3009120 sensitizes RAS or BRAF mutant cancer to CDK4/6 inhibition by abemaciclib via superior inhibition of phospho-RB and suppression of cyclin D1
Chen, S.-H., Gong, X., Zhang, Y., Horn, R. D. V., Yin, T., Huber, L., Burke, T., Manro, J. R., Iversen, P. W., Wu, W., et al. (2017) · Oncogene · doi:10.1038/onc.2017.384 · Cited by 74
Combined BRAF and HSP90 Inhibition in Patients with Unresectable BRAF V600E-Mutant Melanoma
Eroglu, Z., Chen, Y. A., Gibney, G. T., Weber, J. S., Kudchadkar, R. R., Khushalani, N. I., Markowitz, J., Brohl, A. S., Tetteh, L. F., Ramadan, H., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0565 · Cited by 74
In Vivo E2F Reporting Reveals Efficacious Schedules of MEK1/2–CDK4/6 Targeting and mTOR–S6 Resistance Mechanisms
Teh, J. L. F., Cheng, P. F., Purwin, T. J., Nikbakht, N., Patel, P. S., Chervoneva, I., Ertel, A., Fortina, P. M., Kleiber, I., HooKim, K., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0699 · Cited by 73
Exploiting Allosteric Properties of RAF and MEK Inhibitors to Target Therapy-Resistant Tumors Driven by Oncogenic BRAF Signaling
Adamopoulos, C., Ahmed, T. A., Tucker, M. R., Ung, P. M. U., Xiao, M., Karoulia, Z., Amabile, A., Wu, X., Aaronson, S. A., Ang, C., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1351 · Cited by 71
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LBA43 Spartalizumab plus dabrafenib and trametinib (Sparta-DabTram) in patients (pts) with previously untreated BRAF V600–mutant unresectable or metastatic melanoma: Results from the randomized part 3 of the phase III COMBI-i trial
Nathan, P., Dummer, R., Long, G. V., Ascierto, P. A., Tawbi, H., Robert, C., Rutkowski, P. L., Леонов, О. В., Dutriaux, C., Mandalà, M., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.08.2273 · Cited by 67
Belvarafenib, a novel pan-RAF inhibitor, in solid tumor patients harboring BRAF, KRAS, or NRAS mutations: Phase I study.
Kim, T. W., Lee, J., Shin, S. J., Kim, J.-S., Kim, Y. J., Han, H. S., Lee, S. J., Lim, H., Hong, Y.-H., Noh, Y. S., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.3000 · Cited by 49
A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors
Sullivan, R. J., Weber, J. S., Patel, S. P., Dummer, R., Carlino, M. S., Tan, D. S.-W., Lebbé, C., Siena, S., Élez, E., Wollenberg, L. A., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3550 · Cited by 48
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Efficacy and Safety of Trametinib in Non-V600 BRAF Mutant Melanoma: A Phase II Study
Nebhan, C. A., Johnson, D. B., Sullivan, R. J., Amaria, R., Flaherty, K. T., Sosman, J. A., & Davies, M. A. (2021) · The Oncologist · doi:10.1002/onco.13795 · Cited by 45
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RAF dimer inhibition enhances the antitumor activity of MEK inhibitors in K‐RAS mutant tumors
Yuan, X., Tang, Z., Du, R., Yao, Z., Cheung, S., Zhang, X., Wei, J., Zhao, Y., Du, Y., Liu, Y., et al. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12698 · Cited by 40
A Multicenter Phase I Study Evaluating Dual PI3K and BRAF Inhibition with PX-866 and Vemurafenib in Patients with Advanced BRAF V600–Mutant Solid Tumors
Yam, C., Xu, X., Davies, M. A., Gimotty, P. A., Morrissette, J. J. D., Tetzlaff, M. T., Wani, K., Liu, S., Deng, W., Buckley, M. E., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1807 · Cited by 38
Phase 1b/2 trial of ribociclib+binimetinib in metastatic NRAS-mutant melanoma: Safety, efficacy, and recommended phase 2 dose (RP2D).
Schüler, M., Ascierto, P. A., Vos, F. D., Postow, M. A., van Herpen, C. M. L., Carlino, M. S., Sosman, J. A., Berking, C., Long, G. V., Weise, A. M., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.15_suppl.9519 · Cited by 36
Targeting CDK4/6 Represents a Therapeutic Vulnerability in Acquired BRAF/MEK Inhibitor–Resistant Melanoma
Nassar, K. W., Hintzsche, J. D., Bagby, S. M., Espinoza, V. L., Langouët-Astrié, C. J., Amato, C. M., Chimed, T.-S., Fujita, M., Robinson, W. A., Tan, A. C., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-1126 · Cited by 36
A phase Ib/II dose-escalation study evaluating triple combination therapy with a BRAF (encorafenib), MEK (binimetinib), and CDK 4/6 (ribociclib) inhibitor in patients (Pts) with BRAF V600-mutant solid tumors and melanoma.
Ascierto, P. A., Bechter, O. E., Wolter, P., Lebbé, C., Élez, E., Miller, W. H., Long, G. V., Omlin, A. G., Siena, S., Calvo, E., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.15_suppl.9518 · Cited by 32
FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial
Nti, A. A., Serrano, L. W., Sandhu, H. S., Uyhazi, K. E., Edelstein, I. D., Zhou, E. J., Bowman, S., Song, D., Gangadhar, T. C., Schuchter, L. M., et al. (2019) · Retina · doi:10.1097/iae.0000000000002027 · Cited by 31
An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of CDK4/6 Inhibitor-Based Therapies in Melanoma
Teh, J. L. F., Purwin, T. J., Greenawalt, E. J., Chervoneva, I., Goldberg, A. F., Davies, M. A., & Aplin, A. E. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3384 · Cited by 31
A phase Ib trial of belvarafenib in combination with cobimetinib in patients with advanced solid tumors: Interim results of dose-escalation and patients with NRAS-mutant melanoma of dose-expansion.
Shin, S. J., Lee, J., Kim, T. M., Kim, J.-S., Kim, Y. J., Hong, Y. S., Kim, S. Y., Kim, J. E., Lee, D. H., Hong, Y.-H., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.2021.39.15_suppl.3007 · Cited by 31
Abstract PR06: Phase 1b dose-escalation study of trametinib (MEKi) plus palbociclib (CDK4/6i) in patients with advanced solid tumors
Sullivan, R. J., Amaria, R. N., Lawrence, D. P., Brennan, J., Leister, C. A., Singh, R. P., Legos, J., Thurm, H. C., Li, Y., Flaherty, K. T., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.targ-15-pr06 · Cited by 23
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Dual MAPK/CDK Targeting in Melanoma: New Approaches, New Challenges
Sullivan, R. J. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0224 · Cited by 12
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Dose‐escalation trial of combination dabrafenib, trametinib, and AT13387 in patients with BRAF‐mutant solid tumors
Mooradian, M. J., Cleary, J. M., Giobbie‐Hurder, A., Darville, L. N. F., Parikh, A. R., Buchbinder, E. I., Cohen, J. V., Lawrence, D. P., Shapiro, G. I., Keer, H. N., et al. (2023) · Cancer · doi:10.1002/cncr.34730 · Cited by 10
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1387P Phase Ib study of LXH254 + LTT462 in patients with KRAS- or BRAF-mutant NSCLC
Wolf, J. M., Planchard, D., Heist, R. S., Solomon, B., Sebastian, M., Santoro, A., Reguart, N., Stammberger, U. M., Manganelli, L., Wu, H., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.08.1701 · Cited by 9
Abstract LB-B30: First in human, dose escalation trial of the combination of dabrafenib, trametinib, and navitoclax in patients with BRAF mutant solid tumors
Sullivan, R. J., Mehnert, J. M., Tawbi, H., Lawrence, D. P., Flaherty, K. T., Chen, H., Takabe, N., & Davies, M. A. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.targ-17-lb-b30 · Cited by 5
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CTEP 9557: A dose-escalation trial of combination dabrafenib, trametinib, and AT13387 in patients with BRAF mutant solid tumors.
Mooradian, M. J., Cleary, J. M., Cohen, J. V., Lawrence, D. P., Buchbinder, E. I., Giobbie‐Hurder, A., Parikh, A. R., Shapiro, G. I., Darville, L. N. F., Smalley, K. S. M., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.2020.38.15_suppl.3609 · Cited by 4
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Evaluating clinical activity of MAPK targeted therapies (TT) in cancer patients (pts) with non-V600 BRAF mutations: A systematic scoping review and meta-analysis.
Dankner, M., Wang, Y., Fazelzad, R., Spreafico, A., Cescon, D. W., Zogopoulos, G., & Rose, A. A. N. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.2021.39.15_suppl.3089 · Cited by 3
Abstract CT212: Expanded phase 1/2a study of PLX8394, a novel next generation BRAF inhibitor in patients with advanced, unresectable solid tumors with alterations in BRAF
Jankú, F., Sherman, E. J., Yaeger, R. D., Parikh, A., Sullivan, R. J., Feun, L. G., de la Fuente, M. I., Tsai, F. Y.-C., Gordon, M. S., Allen, C. E., et al. (2021) · Cancer Research · doi:10.1158/1538-7445.am2021-ct212 · Cited by 2
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Research works printed but not linked: 2

Corcoran, 2020, Clinical efficacy of combined BRAF, MEK, and PD-1 inhibition in BRAFV600E colorectal cancer patients [abstract]
Janku, 2020, Interim results from a phase 1/2 precision medicine study of PLX8394- a next generation BRAF inhibitor [abstract], S2—3

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The Pan-RAF–MEK Nondegrading Molecular Glue NST-628 Is a Potent and Brain-Penetrant Inhibitor of the RAS–MAPK Pathway with Activity across Diverse RAS- and RAF-Driven Cancers
Ryan, M. B., Quade, B., Schenk, N., Fang, Z., Zingg, M., Cohen, S. E., Swalm, B. M., Li, C., Özen, A., Ye, C., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0139 · Cited by 51
VSIG4+ tumor-associated macrophages mediate neutrophil infiltration and impair antigen-specific immunity in aggressive cancers through epigenetic regulation of SPP1
Pan, Z., Chen, J., Xu, T. C., Cai, A., Han, B., Li, Y., Fang, Z., Yu, D., Wang, S., Zhou, J., et al. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03303-z · Cited by 56

See all 145

Authors: Poulikakos, P. I., Sullivan, R. J., & Yaeger, R.
Affiliations: Icahn School of Medicine at Mount Sinai (US)
Massachusetts General Hospital (US)
Memorial Sloan Kettering Cancer Center (US)
Corresponding author: Poulikakos, Poulikos I.
Sullivan, Ryan J.
Yaeger, Rona
ORCID: Poulikakos, Poulikos I.
Sullivan, Ryan J.
Yaeger, Rona
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2022-04-29
Volume: 28
Issue: 21
Pages: 4618-4628
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-21-2138
PMC: PMC9616966
OpenAlex: W4225136170
Cited by: 145
References: 125
Citations by year: 2026: 29 · 2025: 41 · 2024: 41 · 2023: 31 · 2022: 3
FWCI: 3.02
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (U54 CA224068, P30 CA008748, R01 C233736, R01 CA204314, R01 CA240362, R01CA238229, R01 CA193970, R01 CA229851, UM1 CA186709)
Irma T. Hirschl Trust
Melanoma Research Alliance
Melanoma Research Foundation
Breast Cancer Alliance
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords: BRAF, BRAF inhibitors, BRAF V600 mutation, RAS/MAPK pathway, Raf signaling, combination therapy, melanoma, non-small cell lung cancer, anaplastic thyroid carcinoma, colorectal cancer, drug resistance, drug toxicity, targeted cancer therapy
MeSH terms: Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf

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Molecular Pathways and Mechanisms of BRAF in Cancer Therapy

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