Cited by 354Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesSphingolipid Metabolism and Signaling

The DOI matches its Crossref record; 103 of the 105 references it cites were found in a registry or an index.

Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

Open access

Cox, Adrienne D., Der, Channing J., Philips, Mark R.·2015·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-14-3214PMC PMC4400837

Open this paper in CoChat — free account

Abstract

RAS proteins require membrane association for their biologic activity, making this association a logical target for anti-RAS therapeutics. Lipid modification of RAS proteins by a farnesyl isoprenoid is an obligate step in that association, and is an enzymatic process. Accordingly, farnesyltransferase inhibitors (FTI) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anticancer drugs was widely seen as indicating that blocking RAS membrane association was a flawed approach to cancer treatment. However, a deeper understanding of RAS modification and trafficking has revealed that this was an erroneous conclusion. In the presence of FTIs, KRAS and NRAS, which are the RAS isoforms most frequently mutated in cancer, become substrates for alternative modification, can still associate with membranes, and can still function. Thus, FTIs failed not because blocking RAS membrane association is an ineffective approach, but because FTIs failed to accomplish that task. Recent findings regarding RAS isoform trafficking and the regulation of RAS subcellular localization have rekindled interest in efforts to target these processes. In particular, improved understanding of the palmitoylation/depalmitoylation cycle that regulates RAS interaction with the plasma membrane, endomembranes, and cytosol, and of the potential importance of RAS chaperones, have led to new approaches. Efforts to validate and target other enzymatically regulated posttranslational modifications are also ongoing. In this review, we revisit lessons learned, describe the current state of the art, and highlight challenging but promising directions to achieve the goal of disrupting RAS membrane association and subcellular localization for anti-RAS drug development. Clin Cancer Res; 21(8); 1819–27. ©2015 AACR. See all articles in this CCR Focus section, “Targeting RAS-Driven Cancers.”

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1158/1078-0432.ccr-14-3214

Cites

103 of 103 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A Comprehensive Survey of Ras Mutations in Cancer
Prior, I. A., Lewis, P. D., & Mattos, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2612 · Cited by 2,063 · cited 1×
“The three RAS genes (HRAS, NRAS, KRAS) are the most commonly mutated oncogenes in human cancers (1,2).”
Background
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997
Self-citation
RAS oncogenes: weaving a tumorigenic web
Pylayeva-Gupta, Y., Grabocka, E., & Bar-Sagi, D. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3106 · Cited by 1,789
A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane
Hancock, J. F., Paterson, H., & Marshall, C. J. (1990) · Cell · doi:10.1016/0092-8674(90)90294-o · Cited by 1,042
K- and N-Ras Are Geranylgeranylated in Cells Treated with Farnesyl Protein Transferase Inhibitors
Whyte, D. B., Kirschmeier, P., Hockenberry, T. N., Nunez-Oliva, I., James, L., Catino, J. J., Bishop, W. R., & Pai, J.-K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.22.14459 · Cited by 884
An Acylation Cycle Regulates Localization and Activity of Palmitoylated Ras Isoforms
Rocks, O., Peyker, A., Kahms, M., Verveer, P., Koerner, C., Lumbierres, M., Kuhlmann, J., Waldmann, H., Wittinghofer, A., & Bastiaens, P. (2005) · Science · doi:10.1126/science.1105654 · Cited by 866
Dragging ras back in the ring
Stephen, A. G., Esposito, D., Bagni, R. K., & McCormick, F. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.017 · Cited by 795
Ras history: The saga continues
Cox, A. D., & Der, C. J. (2010) · Small GTPases · doi:10.4161/sgtp.1.1.12178 · Cited by 706
Self-citation
Targeting protein prenylation for cancer therapy
Berndt, N., Hamilton, A. D., & Sebti, S. M. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3151 · Cited by 614 · cited 3×
“Such inhibitors have been developed and some have reached the clinic (16,17), but have been limited by toxicity (21-23).”
Background
Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling
Zimmermann, G., Papke, B., Ismail, S., Vartak, N., Chandra, A., Hoffmann, M., Hahn, S. A., Triola, G., Wittinghofer, A., Bastiaens, P. I. H., et al. (2013) · Nature · doi:10.1038/nature12205 · Cited by 596

Show all 105 references

Sorted by citations

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives
Zhong, L., Li, Y., Xiong, L., Wang, W., Wu, M., Yuan, T., Yang, W. M., Tian, C., Miao, Z., Wang, T., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00572-w · Cited by 1,813
KRAS Mutation: From Undruggable to Druggable in Cancer
Huang, L., Guo, Z., Wang, F., & Fu, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00780-4 · Cited by 1,127
RAS isoforms and mutations in cancer at a glance
Hobbs, G. A., Der, C. J., & Rossman, K. L. (2016) · Journal of Cell Science · doi:10.1242/jcs.182873 · Cited by 973
Self-citation
Recent advances in the development of protein–protein interactions modulators: mechanisms and clinical trials
Lu, H., Zhou, Q., He, J., Jiang, Z., Peng, C., Tong, R., & Shi, J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00315-3 · Cited by 891
Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer
Buscail, L., Bournet, B., & Cordelier, P. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0245-4 · Cited by 721
The interplay between cell signalling and the mevalonate pathway in cancer
Mullen, P., Yu, R., Longo, J., Archer, M. C., & Penn, L. Z. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.76 · Cited by 714
Protein prenylation: unique fats make their mark on biology
Wang, M., & Casey, P. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.11 · Cited by 552
Genetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527
Drugging RAS: know the enemy
Papke, B., & Der, C. J. (2017) · Science · doi:10.1126/science.aam7622 · Cited by 399
Self-citation
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396
Targeting the untargetable KRAS in cancer therapy
Liu, P., Wang, Y., & Li, X. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.03.002 · Cited by 366
Ras Conformational Ensembles, Allostery, and Signaling
Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00542 · Cited by 355
KRAS as a Therapeutic Target
McCormick, F. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2662 · Cited by 320
Squamous Cell Cancers: A Unified Perspective on Biology and Genetics
Dotto, G. P., & Rustgi, A. K. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.04.004 · Cited by 329
KRAS-Mutant non-small cell lung cancer: From biology to therapy
Ferrer, I., Zugazagoitia, J., Herbertz, S., John, W. J., Paz-Ares, L. G., & Schmid‐Bindert, G. (2018) · Lung Cancer · doi:10.1016/j.lungcan.2018.07.013 · Cited by 315
KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target
Román, M., Baraibar, I., López, I., Nadal, E., Rolfo, C., Vicent, S., & Gil-Bazo, I. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0789-x · Cited by 301
Targeting Metalloenzymes for Therapeutic Intervention
Chen, A. Y., Adamek, R. N., Dick, B. L., Credille, C. V., Morrison, C. N., & Cohen, S. M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00201 · Cited by 284
Pathological implication of protein post-translational modifications in cancer
Pan, S., & Chen, R. (2022) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2022.101097 · Cited by 278
Metabolic networks in mutant KRAS-driven tumours: tissue specificities and the microenvironment
Kerk, S. A., Papagiannakopoulos, T. Y., Shah, Y. M., & Lyssiotis, C. A. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00375-9 · Cited by 246
Metabolic Dependencies in RAS -Driven Cancers
Kimmelman, A. C. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2425 · Cited by 230
Interaction between Wnt/β-catenin and RAS-ERK pathways and an anti-cancer strategy via degradations of β-catenin and RAS by targeting the Wnt/β-catenin pathway
Jeong, W.-J., Ro, E. J., & Choi, K.-Y. (2018) · npj Precision Oncology · doi:10.1038/s41698-018-0049-y · Cited by 220
Ras and Rap1: A tale of two GTPases
Shah, S. K., Brock, E. J., Ji, K., & Mattingly, R. R. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.03.005 · Cited by 217
Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis
Huang, J., Jiang, G., Song, Q., Gu, X. Q., Meng, H., Wang, X.-L., Song, H., Chen, L., Lin, Y., Jiang, D. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15144 · Cited by 212
Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view
Lu, S., Jang, H., Gu, S., Zhang, J., & Nussinov, R. (2016) · Chemical Society Reviews · doi:10.1039/c5cs00911a · Cited by 188
Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules
Tulpule, A., Guan, J., Neel, D. S., Allegakoen, H. R., Lin, Y. P., Brown, D., Chou, Y.-T., Heslin, A., Chatterjee, N., Perati, S., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.031 · Cited by 189
KRAS Mutant Pancreatic Cancer: No Lone Path to an Effective Treatment
Zeitouni, D., Pylayeva‐Gupta, Y., Der, C. J., & Bryant, K. L. (2016) · Cancers · doi:10.3390/cancers8040045 · Cited by 191
Self-citation
The RASopathies: from pathogenetics to therapeutics
Hebron, K. E., Hernandez, E. R., & Yohe, M. E. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049107 · Cited by 177
RAS Synthetic Lethal Screens Revisited: Still Seeking the Elusive Prize?
Downward, J. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2180 · Cited by 168
Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities
Bournet, B., Buscail, C., Muscari, F., Cordelier, P., & Buscail, L. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.11.012 · Cited by 173
The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC)
Salgia, R., Pharaon, R. R., Mambetsariev, I., Nam, A., & Sattler, M. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100186 · Cited by 173
Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers
Dillon, M., Lopez, A. R., Lin, E., Sales, D., Perets, R., & Jain, P. (2021) · Cancers · doi:10.3390/cancers13205059 · Cited by 175
Small GTPases
Reiner, D. J. (2016) · WormBook · doi:10.1895/wormbook.1.67.2 · Cited by 164
Mutations in key driver genes of pancreatic cancer: molecularly targeted therapies and other clinical implications
Hu, H.-F., Ye, Z., Qin, Y., Xu, X.-W., Yu, X.-J., Zhuo, Q.-F., & Ji, S.-R. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00584-2 · Cited by 149
ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth
Remsberg, J. R., Suciu, R. M., Zambetti, N. A., Hanigan, T. W., Firestone, A. J., Sheth, A. I., Long, A. M., Ngo, N., Lum, K. M., Henry, C. L., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00785-8 · Cited by 144
Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy
Woensel, M. V., Mathivet, T., Wauthoz, N., Rosière, R., Garg, A. D., Agostinis, P., Mathieu, V., Robert Kiss, A., Lefranc, F., Boon, L., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01279-1 · Cited by 144
Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future
Uras, I. Z., Moll, H. P., & Casanova, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124325 · Cited by 138
Targeting RAS -mutant Cancers: Is ERK the Key?
Ryan, M. B., Der, C. J., Wang‐Gillam, A., & Cox, A. D. (2015) · Trends in cancer · doi:10.1016/j.trecan.2015.10.001 · Cited by 133
Self-citation
The role of wild type RAS isoforms in cancer
Zhou, B., Der, C. J., & Cox, A. D. (2016) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2016.07.012 · Cited by 130
Self-citation
Current therapy of KRAS-mutant lung cancer
Ghimessy, A., Radeczky, P., Laszlo, V., Hegedus, B., Renyi-Vamos, F., Fillinger, J., Klepetko, W., Lang, C., Dome, B., & Megyesfalvi, Z. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09903-9 · Cited by 115
Oncogenic Ras Isoforms Signaling Specificity at the Membrane
Nussinov, R., Tsai, C., & Jang, H. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-2727 · Cited by 124
RAL GTPases: Biology and Potential as Therapeutic Targets in Cancer
Yan, C., & Theodorescu, D. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014415 · Cited by 119
Precise characterization of KRAS4b proteoforms in human colorectal cells and tumors reveals mutation/modification cross-talk
Ntai, I., Fornelli, L., DeHart, C. J., Hutton, J. E., Doubleday, P. F., LeDuc, R. D., van Nispen, A. J., Fellers, R. T., Whiteley, G., Boja, E. S., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716122115 · Cited by 108
GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase
Kuchay, S., Wang, H., Marzio, A., Jain, K., Homer, H., Fehrenbacher, N., Philips, M. R., Zheng, N., & Pagano, M. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0249-3 · Cited by 109
Self-citation
K-Ras protein as a drug target
McCormick, F. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1382-7 · Cited by 105
Improving prospects for targeting RAS
Singh, H., Longo, D. L., & Chabner, B. A. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.62.1052 · Cited by 107
BRAF and KRAS mutations in metastatic colorectal cancer: future perspectives for personalized therapy
Li, Z., Zhao, L., Yu, L., & Wei, M. (2020) · Gastroenterology report · doi:10.1093/gastro/goaa022 · Cited by 110
Small-Molecule Inhibitors Directly Targeting KRAS as Anticancer Therapeutics
Chen, H., Smaill, J. B., Liu, T., Ding, K., & Lu, X. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01312 · Cited by 104
Wild type Kirsten rat sarcoma is a novel microRNA-622-regulated therapeutic target for hepatocellular carcinoma and contributes to sorafenib resistance
Dietrich, P., Koch, A., FRITZ, V. K., Hartmann, A., Bosserhoff, A., & Hellerbrand, C. (2017) · Gut · doi:10.1136/gutjnl-2017-315402 · Cited by 99
Farnesyl diphosphate synthase is important for the maintenance of glioblastoma stemness
Kim, H. Y., Kim, D.-K., Bae, S.-H., Gwak, H., Jeon, J. H., Kim, J.-K., Lee, B. I., You, H. J., Shin, D. H., Kim, Y.-H., et al. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0166-2 · Cited by 98
Biomolecular Condensates and Their Links to Cancer Progression
Cai, D., Liu, Z. J., & Lippincott‐Schwartz, J. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2021.01.002 · Cited by 97
Novel p21-Activated Kinase 4 (PAK4) Allosteric Modulators Overcome Drug Resistance and Stemness in Pancreatic Ductal Adenocarcinoma
Aboukameel, A., Muqbil, I., Senapedis, W. T., Baloglu, E., Landesman, Y., Shacham, S., Kauffman, M. G., Philip, P. A., Mohammad, R. M., & Azmi, A. S. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0205 · Cited by 97
Membrane-lipid therapy: A historical perspective of membrane-targeted therapies — From lipid bilayer structure to the pathophysiological regulation of cells
Escribá, P. V. (2017) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2017.05.017 · Cited by 98
RNA G-Quadruplexes in Kirsten Ras ( KRAS ) Oncogene as Targets for Small Molecules Inhibiting Translation
Miglietta, G., Cogoi, S., Marinello, J., Capranico, G., Tikhomirov, A. S., Shchekotikhin, A. E., & Xodo, L. E. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00622 · Cited by 94
A New View of Ras Isoforms in Cancers
Nussinov, R., Tsai, C., Chakrabarti, M., & Jang, H. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-1536 · Cited by 92
Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development
Chen, T. C., da Fonseca, C. O., & Schönthal, A. H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123905 · Cited by 90
Drugging “undruggable” genes for cancer treatment: Are we making progress?
Duffy, M. J., & Crown, J. P. (2020) · International Journal of Cancer · doi:10.1002/ijc.33197 · Cited by 86
Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS
Yin, G., Huang, J., Petela, J., Jiang, H., Zhang, Y., Gong, S., Wu, J., Liu, B., Shi, J., & Gao, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01441-4 · Cited by 98
Photo-induced radical thiol–ene chemistry: a versatile toolbox for peptide-based drug design
Ahangarpour, M., Kavianinia, I., Harris, P. W. R., & Brimble, M. A. (2021) · Chemical Society Reviews · doi:10.1039/d0cs00354a · Cited by 87
Calmodulin and PI3K Signaling in KRAS Cancers
Nussinov, R., Wang, G., Tsai, C., Jang, H., Lu, S., Banerjee, A., Zhang, J., & Gaponenko, V. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.01.007 · Cited by 78
Tipifarnib Inhibits HRAS-Driven Dedifferentiated Thyroid Cancers
Untch, B. R., Anjos, V. D., García-Rendueles, M. E. R., Knauf, J. A., Krishnamoorthy, G. P., Saqcena, M., Bhanot, U. K., Socci, N. D., Ho, A. L., Ghossein, R. A., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-1925 · Cited by 78
Direct Modulation of Small GTPase Activity and Function
Cromm, P. M., Spiegel, J., Grossmann, T. N., & Waldmann, H. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201504357 · Cited by 80
Direct Attack on RAS: Intramolecular Communication and Mutation-Specific Effects
Marcus, K., & Mattos, C. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2148 · Cited by 75
Targeting RAS signaling pathway as a potential therapeutic target in the treatment of colorectal cancer
Bahrami, A., Hassanian, S. M., Shahidsales, S., Farjami, Z., Hasanzadeh, M., Anvari, K., Aledavood, A., Maftouh, M., Ferns, G. A., Khazaei, M., et al. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25890 · Cited by 74
KRAS-Mutant Non-Small Cell Lung Cancer: An Emerging Promisingly Treatable Subgroup
Xie, M., Xu, X., & Fan, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.672612 · Cited by 80
MicroRNA regulation of K-Ras in pancreatic cancer and opportunities for therapeutic intervention
Karmakar, S., Kaushik, G., Nimmakayala, R. K., Rachagani, S., Ponnusamy, M. P., & Batra, S. K. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.11.020 · Cited by 75
A review of the biological and clinical implications of RAS-MAPK pathway alterations in neuroblastoma
Mlakar, V., Morel, E., Mlakar, S. J., Ansari, M., & Gumy‐Pause, F. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01967-x · Cited by 72
New tricks for human farnesyltransferase inhibitor: cancer and beyond
Wang, J., Yao, X., & Huang, J. Y. (2017) · MedChemComm · doi:10.1039/c7md00030h · Cited by 73
The cornerstone K-RAS mutation in pancreatic adenocarcinoma: From cell signaling network, target genes, biological processes to therapeutic targeting
Jonckheere, N., Vasseur, R., & SEUNINGEN, I. V. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.01.002 · Cited by 73
Oncogenic KRAS signaling and YAP1/β-catenin: Similar cell cycle control in tumor initiation
Nussinov, R., Tsai, C., Jang, H., Korcsmáros, T., & Csermely, P. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.04.001 · Cited by 70
Integration of Rap1 and Calcium Signaling
Kosuru, R., & Chrzanowska‐Wodnicka, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051616 · Cited by 70
Targeted therapies for KRAS-mutant non-small cell lung cancer: from preclinical studies to clinical development—a narrative review
Santarpia, M., Ciappina, G., Spagnolo, C. C., Squeri, A., Passalacqua, M. I., Aguilar, A., Gonzalez-Cao, M., Giovannetti, E., Silvestris, N., & Rosell, R. (2023) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-639 · Cited by 65
Post-translational modification of RAS proteins
Campbell, S. L., & Philips, M. R. (2021) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2021.06.015 · Cited by 68
Self-citation
Progress in targeting RAS with small molecule drugs
McCormick, F. P. (2019) · Biochemical Journal · doi:10.1042/bcj20170441 · Cited by 64
KRAS-enhanced macropinocytosis and reduced FcRn-mediated recycling sensitize pancreatic cancer to albumin-conjugated drugs
Liu, H., Sun, M., Liu, Z., Kong, C., Kong, W., Ye, J., Gong, J., Huang, D. C. S., & Qian, F. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.01.014 · Cited by 67
Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth
Howe, E. N., Burnette, M. D., Justice, M. E., Schnepp, P. M., Hedrick, V., Clancy, J. W., Guldner, I. H., Lamere, A. T., Li, J., Aryal, U. K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16832-2 · Cited by 68
High expression of RAD51 promotes DNA damage repair and survival in KRAS-mutant lung cancer cells
Hu, J., Zhang, Z., Zhao, L., Li, L., Zuo, W., & Han, L. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.2.213 · Cited by 62
Targeting KRAS Mutant in Non-Small Cell Lung Cancer: Novel Insights Into Therapeutic Strategies
Désage, A.-L., Léonce, C., Swalduz, A., & Ortiz‐Cuaran, S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.796832 · Cited by 65
Structure of two G-quadruplexes in equilibrium in the KRAS promoter
Marquevielle, J., Robert, C., Lagrabette, O., Wahid, M., Bourdoncle, A., Xodo, L. E., Mergny, J., & Salgado, G. F. J. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa387 · Cited by 63
Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets
Tate, E. W., Soday, L., de la Lastra, A. L., Wang, M., & Lin, H. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00666-x · Cited by 63
Personal Mutanomes Meet Modern Oncology Drug Discovery and Precision Health
Cheng, F., Liang, H., Butte, A. J., Eng, C., & Nussinov, R. (2018) · Pharmacological Reviews · doi:10.1124/pr.118.016253 · Cited by 58
Targeting KRAS Directly
McCormick, F. P. (2018) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050216-122010 · Cited by 58
Advancing RAS/RASopathy therapies: An NCI‐sponsored intramural and extramural collaboration for the study of RASopathies
Gross, A. M., Frone, M. N., Gripp, K. W., Gelb, B. D., Schoyer, L., Schill, L., Stronach, B. E., Biesecker, L. G., Esposito, D., Hernandez, E. R., et al. (2020) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61485 · Cited by 57
Treatment of NRAS -mutated advanced or metastatic melanoma: rationale, current trials and evidence to date
Boespflug, A. M., Caramel, J., Dalle, S., & Thomas, L. (2017) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834017708160 · Cited by 57
Intrinsic protein disorder in oncogenic KRAS signaling
Nussinov, R., Jang, H., Tsai, C., Liao, T.-J., Li, S., Fushman, D., & Zhang, J. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2564-3 · Cited by 58
Wild-type KRAS is a novel therapeutic target for melanoma contributing to primary and acquired resistance to BRAF inhibition
Dietrich, P., Kuphal, S., Spruß, T., Hellerbrand, C., & Bosserhoff, A. (2017) · Oncogene · doi:10.1038/onc.2017.391 · Cited by 54
K-Ras and its inhibitors towards personalized cancer treatment: Pharmacological and structural perspectives
Asati, V., Mahapatra, D. K., & Bharti, S. K. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.09.049 · Cited by 56
Oncogenic KRAS Targets MUC16/CA125 in Pancreatic Ductal Adenocarcinoma
Liang, C., Qin, Y., Zhang, B., Ji, S., Shi, S., Xu, W., Liu, J., Xiang, J., Liang, D., Hu, Q., et al. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0296 · Cited by 53
Rce1: mechanism and inhibition
Hampton, S. E., Dore, T. M., & Schmidt, W. K. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1431606 · Cited by 53
Cysteine-based regulation of redox-sensitive Ras small GTPases
Messina, S., Simone, G. D., & Ascenzi, P. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101282 · Cited by 52
Emerging Targets in Non-Small Cell Lung Cancer
Liu, L., Soler, J., Reckamp, K. L., & Sankar, K. N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251810046 · Cited by 58
KRAS mutant lung cancer: progress thus far on an elusive therapeutic target
Bhattacharya, S., Socinski, M. A., & Burns, T. F. (2015) · Clinical and Translational Medicine · doi:10.1186/s40169-015-0075-0 · Cited by 53
Strengths and Weaknesses of Pre-Clinical Models for Human Melanoma Treatment: Dawn of Dogs’ Revolution for Immunotherapy
Barutello, G., Rolih, V., Arigoni, M., Tarone, L., Conti, L., Quaglino, E., Buracco, P., Cavallo, F., & Riccardo, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030799 · Cited by 51
MEK inhibitors for the treatment of NRAS mutant melanoma
Sarkisian, S., & Davar, D. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s131721 · Cited by 52
Neuroblastoma RAS Viral Oncogene Homolog (NRAS) Is a Novel Prognostic Marker and Contributes to Sorafenib Resistance in Hepatocellular Carcinoma
Dietrich, P., Gaza, A., Wormser, L., FRITZ, V. K., Hellerbrand, C., & Bosserhoff, A. (2019) · Neoplasia · doi:10.1016/j.neo.2018.11.011 · Cited by 49
FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis
Ponnusamy, A., Sinha, S., Hyde, G. D., Borland, S. J., Taylor, R. F., Pond, E., Eyre, H. J., Inkson, C. A., Gilmore, A. P., Ashton, N., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0196232 · Cited by 48
A Potent Isoprenylcysteine Carboxylmethyltransferase (ICMT) Inhibitor Improves Survival in Ras-Driven Acute Myeloid Leukemia
Marín‐Ramos, N. I., Balabasquer, M., Ortega-Nogales, F. J., Torrecillas, I. R., Gil-Ordóñez, A., Marcos‐Ramiro, B., Aguilar-Garrido, P., Cushman, I., Romero, A., Medrano, F. J., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00145 · Cited by 51
Self-citation
Mechanisms of Ras Membrane Organization and Signaling: Ras Rocks Again
Abankwa, D., & Gorfe, A. A. (2020) · Biomolecules · doi:10.3390/biom10111522 · Cited by 46
Membrane curvature sensing of the lipid-anchored K-Ras small GTPase
Hong, L., Mu, H., Jean-Francois, F. L., Lakshman, B., Sarkar‐Banerjee, S., Zhuang, Y., Zeng, Y., Gao, W., Zaske, A. M., Nissley, D. V., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201900343 · Cited by 48
Toward the identification of ZDHHC enzymes required for palmitoylation of viral protein as potential drug targets
Gadalla, M. R., & Veit, M. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1696306 · Cited by 44
Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms
Lau, H. Y., Tang, J., Casey, P. J., & Wang, M. (2017) · Oncogene · doi:10.1038/onc.2016.508 · Cited by 46

Authors: Cox, A. D., Der, C. J., & Philips, M. R.
Affiliations: University of North Carolina at Chapel Hill (US)
NYU Langone Health (US)
ORCID: Cox, Adrienne D.
Der, Channing J.
Philips, Mark R.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2015-04-14
Volume: 21
Issue: 8
Pages: 1819-1827
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-14-3214
PMC: PMC4400837
OpenAlex: W2129653056
Cited by: 351
References: 105
Citations by year: 2026: 11 · 2025: 15 · 2024: 19 · 2023: 31 · 2022: 30 · 2021: 46 · 2020: 39 · 2019: 29 · 2018: 43 · 2017: 40 · 2016: 28 · 2015: 18
FWCI: 4.17
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
UNC Libraries
Funders: Pancreatic Cancer Action Network
National Institutes of Health (5r01ca042978-30)
National Cancer Institute (R01CA116034, R01CA175747, R01CA163489, R01-CA042978, R21CA179193)
National Institute of General Medical Sciences (R01GM055279)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords: farnesyltransferase inhibitors, KRAS, NRAS, depalmitoylation, post-translational modification, RAS-driven cancers
MeSH terms: Acetyltransferases, Acylation, Animals, Antineoplastic Agents, Carrier Proteins, Cell Membrane, Humans, Neoplasms, Endopeptidases, Phosphorylation, Protein Kinase C, Thiolester Hydrolases, Signal Transduction, Proto-Oncogene Proteins p21(ras), Protein Prenylation, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Alkyl and Aryl Transferases, Amino Acid Motifs, Protein Transport, Protein Interaction Domains and Motifs, Drug Discovery, Molecular Targeted Therapy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks