CDK4/6 inhibitors have potent activity in combination with pathway selective therapeutic agents in models of pancreatic cancer
Open accessAbstract
// Jorge Franco 1 , Agnieszka K. Witkiewicz 1,2 and Erik S. Knudsen 1,2 1 Department of Pathology , UT Southwestern, Dallas TX 2 Simmons Cancer Center, UT Southwestern, Dallas TX Correspondence: Erik S. Knudsen, email: // Agnieszka K. Witkiewicz, email: // Keywords : RB, CDK4/6, palbocicllb, pancreatic cancer, E2F Received : July 10, 2014 Accepted : July 26, 2014 Published : July 26, 2014 Abstract Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, in part, due to the therapy-recalcitrant nature of the disease. Loss of the CDK4/6 inhibitor CDKN2A is a signature genetic event in PDA. Therefore, PDA may be amenable to treatment with pharmaceutical CDK4/6 inhibitors. Surprisingly, response to CDK4/6 inhibition was highly variable in PDA models, and was associated with differential suppression of RB-regulated gene expression. Mitotic genes were repressed and FOXM1 was uniformly attenuated; however, genes involved in DNA replication were uniquely suppressed in sensitive models. Aberrant induction of Cyclin E1 was associated with resistance, and knockdown demonstrated synergistic suppression of the cell cycle with CDK4/6 inhibition. Combination therapies are likely required for the effective treatment of disease, and drug screening demonstrated additive/antagonistic interactions with CDK4/6 inhibitors. Agents dependent on mitotic progression (taxanes/PLK1 inhibitors) were antagonized by CDK4/6 inhibition, while the response to 5-FU and gemcitabine exhibited drug specific interactions. PI3K/MTOR and MEK inhibitors potently cooperated with CDK4/6 inhibition. These agents were synergistic with CDK4/6 inhibition, blocked the aberrant upregulation of Cyclin E1, and yielded potent inhibition of tumor cell growth. Together, these data identify novel mechanisms of resistance to CDK4/6 inhibitions and provide a roadmap for combination therapies in the treatment of PDA.
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
Cites
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?
Preclinical studies show synergistic effects of CDK4/6 inhibition and MAP kinase inhibition in melanoma and pancreatic cancer models.
“preclinical synergistic effects of CDK4/6 inhibition and MAP kinase inhibition in melanoma and pancreatic cancer models has stimulated substantial interest in the development of these combinations (106-108)”
From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [108]
Combined CDK4 and MEK inhibition increased apoptosis and/or reduced viability in colony formation assays in human melanoma and pancreatic cancer cell lines.
“combined CDK4 and MEK inhibition has led to increased apoptosis and/or reduced viability in colony formation assays in human melanoma and pancreatic cancer cell lines.”
From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [108]
Alterations in expression of cyclin E, p27Kip1, and D-type cyclins have been demonstrated in adaptation to CDK4/6 inhibition, potentially contributing to acquired resistance.
“alterations in expression of such cell cycle regulators, including cyclin E and p27Kip1, as well as D-type cyclins themselves, have been demonstrated in adaptation to CDK4/6 inhibition, potentially contributing to acquired resistance (108, 134-136).”
From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [108]
p16INK4A-deficient pancreatic cancer cell lines may be inherently resistant to CDK4/6 inhibitors; synergistic compromise of proliferation and viability has been shown with PI3K inhibitors and IGF1R inhibitors in vitro and in vivo.
“p16INK4A-deficient pancreatic cancer cell lines may be inherently resistant to CDK4/6 inhibitors; synergistic compromise of cell proliferation and viability have been demonstrated with PI3K inhibitors (108), as well as with inhibitors of IGF1R both in vitro and in vivo (120).”
From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [108]
Some adaptations to CDK4/6 inhibition are reversible after drug removal, suggesting potential value of intermittent dosing schedules for maintaining cell cycle arrest.
“some of these adaptations are reversible after drug removal suggesting, perhaps counter-intuitively, the potential value of intermittent dosing schedules for maintenance of cell cycle arrest.”
From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [108]
CDK4 inhibition was reported to antagonize drugs that require entry into mitosis for their efficacy, such as taxanes.
“CDK4 inhibition was reported to antagonize drugs that require entry into mitosis for their efficacy, such as taxanes49, probably due to inhibited cell cycle progression.”
From CDK4 inhibition diminishes p53 activation by MDM2 antagonists (2018) · cites this paper as [49]
CDK4 inhibitors were found to cooperate with inhibitors of signaling kinases, such as MEK and PI3K.
“On the other hand, CDK4 inhibitors were found to cooperate with inhibitors of signaling kinases, such as MEK and PI3K49,50.”
From CDK4 inhibition diminishes p53 activation by MDM2 antagonists (2018) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · cited 1× · see citing works
“In the context of PDA, it has been hypothesized that p16ink4a loss is selected for to enable the progression of KRAS mutated cells [10-13].”
BackgroundA new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
Serrano, M., Hannon, G. J., & Beach, D. (1993) · Nature · doi:10.1038/366704a0 · Cited by 3,650 · see citing works
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · cited 1× · see citing works
“In the context of PDA, it has been hypothesized that p16ink4a loss is selected for to enable the progression of KRAS mutated cells [10-13].”
BackgroundFinn, R. S., Dering, J., Conklin, D., Kalous, O., Cohen, D. J., Desai, A. J., Ginther, C., Atefi, M., Chen, I., Fowst, C., et al. (2009) · Breast Cancer Research · doi:10.1186/bcr2419 · Cited by 1,398 · see citing works
Biological determinants of endocrine resistance in breast cancer
Musgrove, E. A., & Sutherland, R. L. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2713 · Cited by 1,254 · see citing works
Fry, D. W., Harvey, P. J., Keller, P. R., Elliott, W. L., Meade, M., Trachet, E., Albassam, M., Zheng, X., Leopold, W. R., Pryer, N. K., et al. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.1427.3.11 · Cited by 1,236 · cited 2× · see citing works
“In preclinical models, activation of RB via CDK4/6 inhibition can induce senescent-like arrest [29, 30, 35-39].”
BackgroundRetinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16
Lukas, J., Parry, D., Aagaard, L., Mann, D. J., Bartkova, J., Strauss, M., Peters, G., & Bartek, J. (1995) · Nature · doi:10.1038/375503a0 · Cited by 899 · see citing works
Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma
Zuo, L., Weger, J., Yang, Q., Goldstein, A. M., Tucker, M. A., Walker, G. J., Hayward, N., & Dracopoli, N. C. (1996) · Nature Genetics · doi:10.1038/ng0196-97 · Cited by 818 · cited 1× · see citing works
“p16ink4a-mediated arrest is selectively bypassed by CDK4 mutations that disrupt the association with the inhibitor [24, 25].”
BackgroundPavletich, N. P. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2640 · Cited by 746 · see citing works
Presence of Somatic Mutations in Most Early-Stage Pancreatic Intraepithelial Neoplasia
Kanda, M., Matthaei, H., Wu, J., Hong, S., Yu, J., Borges, M., Hruban, R. H., Maitra, A., Kinzler, K., Vogelstein, B., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.12.042 · Cited by 741 · see citing works
Bardeesy, N. M., Aguirre, A. J., Chu, G. C., Cheng, K., Lopez, L. V., Hezel, A. F., Feng, B., Brennan, C. W., Weissleder, R., Mahmood, U., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601273103 · Cited by 575 · see citing works
Anders, L., Ke, N., Hydbring, P., Choi, Y. J., Widlund, H. R., Chick, J. M., Zhai, H., Vidal, M., Gygi, S. P., Braun, P., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.10.001 · Cited by 543 · see citing works
Russo, A. A., Tong, L., Lee, J.-O., Jeffrey, P. D., & Pavletich, N. P. (1998) · Nature · doi:10.1038/26155 · Cited by 524 · see citing works
Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition
Koh, J., Enders, G. H., David Dynlacht, B., & Harlow, E. (1995) · Nature · doi:10.1038/375506a0 · Cited by 516 · see citing works
Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6
Toogood, P. L., Harvey, P. J., Repine, J. T., Sheehan, D. J., VanderWel, S. N., Zhou, H., Keller, P. R., McNamara, D. J., Sherry, D., Zhu, T., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm049354h · Cited by 513 · see citing works
Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation.Preprint
Xiong, Y., Zhang, H., & Beach, D. (1993) · Genes & Development · doi:10.1101/gad.7.8.1572 · Cited by 507 · see citing works
Dickson, M. A., Tap, W. D., Keohan, M. L., D'Angelo, S. P., Gounder, M. M., Antonescu, C. R., Landa, J., Qin, L.-X., Rathbone, D. D., Condy, M. M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.46.5476 · Cited by 399 · see citing works
Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure
Dean, J. L., Thangavel, C., McClendon, A. K., Reed, C. A., & Knudsen, E. S. (2010) · Oncogene · doi:10.1038/onc.2010.154 · Cited by 393 · see citing works
Self-citationDissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence
Chicas, A., Wang, X., Zhang, C., McCurrach, M., Zhao, Z., Mert, O., Dickins, R. A., Narita, M., Zhang, M., & Lowe, S. W. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.023 · Cited by 388 · see citing works
Inhibition of Ras-Induced Proliferation and Cellular Transformation by p16 INK4
Serrano, M., Gómez-Lahoz, E., DePinho, R. A., Beach, D., & Bar‐Sagi, D. (1995) · Science · doi:10.1126/science.7809631 · Cited by 373 · see citing works
Infante, J. R., Somer, B. G., Park, J. O., Li, C., Scheulen, M. E., Kasubhai, S. M., Oh, D., Liu, Y., Redhu, S., Steplewski, K. M., et al. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.04.024 · Cited by 370 · see citing works
Flaherty, K. T., LoRusso, P. M., DeMichele, A., Abramson, V. G., Courtney, R., Randolph, S. S., Shaik, M. N., Wilner, K. D., O'Dwyer, P. J., & Schwartz, G. K. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0509 · Cited by 366 · see citing works
Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma
Kwong, L. N., Costello, J. C., Liu, H., Jiang, S., Helms, T. L., Langsdorf, A. E., Jakubosky, D., Genovese, G., Muller, F. L., Jeong, J. H., et al. (2012) · Nature Medicine · doi:10.1038/nm.2941 · Cited by 358 · see citing works
Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines.
Shapiro, G. I., Edwards, C. D., Kobzik, L., Godleski, J. J., Richards, W. G., Sugarbaker, D. J., & Rollins, B. J. (1995) · PubMed · Cited by 340 · see citing works
Michaud, K., Solomon, D. A., Oermann, E. K., Kim, J.-S., Zhong, W.-Z., Prados, M. D., Ozawa, T., James, C. D., & Waldman, T. A. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4559 · Cited by 321 · see citing works
The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expressionPreprint
Sadasivam, S., Duan, S., & DeCaprio, J. A. (2012) · Genes & Development · doi:10.1101/gad.181933.111 · Cited by 311 · see citing works
Expression of p16 and Retinoblastoma Determines Response to CDK4/6 Inhibition in Ovarian Cancer
Konecny, G. E., Winterhoff, B. J. N., Kolarova, T. R., Qi, J., Manivong, K., Dering, J., Yang, G., Chalukya, M., Wang, H.-J., Anderson, L. A., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2307 · Cited by 303 · see citing works
Thangavel, C., Dean, J. L., Ertel, A., Knudsen, K. E., Aldaz, C. M., Witkiewicz, A. K., Clarke, R., & Knudsen, E. S. (2011) · Endocrine Related Cancer · doi:10.1530/erc-10-0262 · Cited by 302 · see citing works
Self-citationSelective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma
Leonard, J. P., LaCasce, A. S., Smith, M. R., Noy, A., Chirieac, L. R., Rodig, S. J., Yu, J. Q., Vallabhajosula, S., Schoder, H., English, P., et al. (2012) · Blood · doi:10.1182/blood-2011-10-388298 · Cited by 299 · see citing works
Therapeutic Advances in Pancreatic Cancer
Paulson, A. S., Cao, H. S. T., Tempero, M. A., & Lowy, A. M. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.01.078 · Cited by 291 · see citing works
Witkiewicz, A. K., Knudsen, K. E., Dicker, A. P., & Knudsen, E. S. (2011) · Cell Cycle · doi:10.4161/cc.10.15.16776 · Cited by 286 · see citing works
Self-citationThe p16-cyclin D/Cdk4-pRb pathway as a functional unit frequently altered in melanoma pathogenesis.
Bártková, J., Lukáš, J., Guldberg, P., Alsner, J., Kirkin, A. F., Zeuthen, J., & Bártek, J. (1996) · PubMed · Cited by 275 · see citing works
Schwartz, G. K., LoRusso, P. M., Dickson, M. A., Randolph, S. S., Shaik, M. N., Wilner, K. D., Courtney, R., & O'Dwyer, P. J. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.177 · Cited by 260 · see citing works
Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy
Roberts, P. J., Bisi, J. E., Strum, J. C., Combest, A. J., Darr, D. B., Usary, J. E., Zamboni, W. C., Wong, K.-K., Perou, C. M., & Sharpless, N. E. (2012) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djs002 · Cited by 255 · see citing works
Molecular pathways: CDK4 inhibitors for cancer therapy
Dickson, M. A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1551 · Cited by 245 · see citing works
Philip, P. A., Mooney, M., Jaffe, D., Eckhardt, G., Moore, M. J., Meropol, N. J., Emens, L. A., O'Reilly, E. M., Korc, M., Ellis, L. M., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.21.9022 · Cited by 240 · see citing works
Dean, J. L., McClendon, A. K., Hickey, T. E., Butler, L. M., Tilley, W. D., Witkiewicz, A. K., & Knudsen, E. S. (2012) · Cell Cycle · doi:10.4161/cc.21195 · Cited by 226 · see citing works
Self-citationEvolution and dynamics of pancreatic cancer progression
Yachida, S., & Iacobuzio–Donahue, C. A. (2013) · Oncogene · doi:10.1038/onc.2013.29 · Cited by 185 · see citing works
Mouse models of pancreatic cancer.
Herreros-Villanueva, M., Hijona, E., Cosme, Á., & Bujanda, L. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i12.1286 · Cited by 169 · see citing works
CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy
McClendon, A. K., Dean, J. L., Rivadeneira, D. B., Yu, J. E., Reed, C. A., Gao, E., Farber, J. L., Force, T. L., Koch, W. J., & Knudsen, E. S. (2012) · Cell Cycle · doi:10.4161/cc.21127 · Cited by 163 · see citing works
Self-citationModification of the DNA Damage Response by Therapeutic CDK4/6 Inhibition
Dean, J. L., McClendon, A. K., & Knudsen, E. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.365494 · Cited by 156 · see citing works
Self-citationKaye, F. J. (2002) · Oncogene · doi:10.1038/sj.onc.1205834 · Cited by 153 · see citing works
Caldon, C. E., Sergio, C. M., Kang, J., Muthukaruppan, A., Boersma, M. N., Stone, A. M., Barraclough, J., Lee, C. S., Black, M. A., Miller, L. D., et al. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0963 · Cited by 151 · see citing works
Lange, C. A., & Yee, D. (2011) · Endocrine Related Cancer · doi:10.1530/erc-11-0112 · Cited by 147 · see citing works
Liu, F., & Korc, M. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0562 · Cited by 128 · see citing works
Rivadeneira, D. B., Mayhew, C. N., Thangavel, C., Sotillo, E., Reed, C. A., Graña, X., & Knudsen, E. S. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.01.007 · Cited by 127 · see citing works
Self-citationMarkey, M. P., Angus, S. P., Strobeck, M. W., Williams, S., Gunawardena, R. W., Aronow, B. J., & Knudsen, E. S. (2002) · PubMed · Cited by 123 · see citing works
Self-citationLeontieva, O. V., & Blagosklonny, M. V. (2013) · Cell Cycle · doi:10.4161/cc.26130 · Cited by 119 · see citing works
Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer
Rocca, A., Farolfi, A., Bravaccini, S., Schirone, A., & Amadori, D. (2013) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2014.870555 · Cited by 108 · see citing works
Is Cyclin D1-CDK4 kinase a bona fide cancer target?
Malumbres, M., & Barbacid, M. (2006) · Cancer Cell · doi:10.1016/j.ccr.2005.12.026 · Cited by 96 · see citing works
MEK drives cyclin D1 hyperelevation during geroconversion
Leontieva, O. V., Demidenko, Z. N., & Blagosklonny, M. V. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.86 · Cited by 90 · see citing works
Retinoblastoma Tumor Suppressor Targets dNTP Metabolism to Regulate DNA Replication
Angus, S. P., Wheeler, L. J., Ranmal, S. A., Zhang, X., Markey, M. P., Mathews, C. K., & Knudsen, E. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205911200 · Cited by 87 · see citing works
Self-citationSmarter drugs emerging in pancreatic cancer therapy
Kleger, A., Perkhofer, L., & Seufferlein, T. T. W. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu013 · Cited by 77 · see citing works
Genetic Progression of Pancreatic Cancer
Cowan, R. W., & Maitra, A. (2014) · The Cancer Journal · doi:10.1097/ppo.0000000000000011 · Cited by 76 · see citing works
Lukas, J., Sørensen, C. S., Lukas, C., Santoni‐Rugiu, E., & Bártek, J. (1999) · Oncogene · doi:10.1038/sj.onc.1202777 · Cited by 73 · see citing works
Blockbuster dreams for Pfizer's CDK inhibitor
Guha, M. (2013) · Nature Biotechnology · doi:10.1038/nbt0313-187a · Cited by 43 · see citing works
Defining New Paradigms for the Treatment of Pancreatic Cancer
Almhanna, K., & Philip, P. A. (2011) · Current Treatment Options in Oncology · doi:10.1007/s11864-011-0150-8 · Cited by 39 · see citing works
Calbó, J., Marotta, M., Cascalló, M., Roig, J. M., Gelpí, J. L., Fueyo-Margareto, J., & Mazo, A. (2001) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7700374 · Cited by 38 · see citing works
Chen, F., Li, Y., Lu, Z., Gao, J., & Chen, J. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.12.2183 · Cited by 9 · see citing works
Comparison of three methods for 17α-Hydroxyprogesterone
Castracane, V. D., & Gimpel, T. (1997) · Journal of Clinical Laboratory Analysis · doi:10.1002/(sici)1098-2825(1997)11:4 · Cited by 9 · see citing works
Palbociclib Ups PFS in HER2−/ER+ Breast Cancer
(2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-nb2014-053 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The PI3K Pathway in Human Disease
Fruman, D. A., Chiu, H., Hopkins, B. D., Bagrodia, S., Cantley, L. C., & Abraham, R. T. (2017) · Cell · doi:10.1016/j.cell.2017.07.029 · Cited by 2,749 · see citing works
The history and future of targeting cyclin-dependent kinases in cancer therapy
Asghar, U., Witkiewicz, A. K., Turner, N. C., & Knudsen, E. S. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4504 · Cited by 1,767 · see citing works
Self-citationWhole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets
Witkiewicz, A. K., McMillan, E. A., Balaji, U., Baek, G., Lin, W.-C., Mansour, J., Mollaee, M., Wagner, K.-U., Koduru, P., Yopp, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms7744 · Cited by 1,115 · see citing works
Self-citationTargeting CDK4 and CDK6: From Discovery to Therapy
Sherr, C. J., Beach, D., & Shapiro, G. I. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0894 · Cited by 936 · see citing works
Herrera-Abreu, M. T., Palafox, M., Asghar, U. S., Rivas, M. A., Cutts, R. J., García-Murillas, I., Pearson, A., Guzmán, M., Rodríguez, O., Grueso, J., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-0728 · Cited by 768 · see citing works
Aung, K. L., Fischer, S. E., Denroche, R. E., Jang, G.-H., Dodd, A., Creighton, S., Southwood, B., Liang, S.-B., Chadwick, D., Zhang, A., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2994 · Cited by 618 · see citing works
MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road
Caunt, C. J., Sale, M. J., Smith, P. D., & Cook, S. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4000 · Cited by 606 · see citing works
Targeting CDK4/6 in patients with cancer
Hamilton, E. P., & Infante, J. R. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.03.002 · Cited by 486 · see citing works
RB1 : a prototype tumor suppressor and an enigmaPreprint
Dyson, N. J. (2016) · Genes & Development · doi:10.1101/gad.282145.116 · Cited by 437 · see citing works
Therapeutic strategies to target RAS-mutant cancers
Ryan, M. B., & Corcoran, R. B. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0105-0 · Cited by 420 · see citing works
Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer
Formisano, L., Lu, Y., Servetto, A., Hanker, A. B., Jansen, V. M., Bauer, J. A., Sudhan, D. R., Zotano, Á. G., Croessmann, S., Guo, Y. P., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09068-2 · Cited by 409 · see citing works
Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review
Pandey, K., An, H. J., Kim, S., Lee, S. A., Kim, S., Lim, S. M., Kim, G. M., Sohn, J., & Moon, Y. W. (2018) · International Journal of Cancer · doi:10.1002/ijc.32020 · Cited by 366 · see citing works
Cell-Cycle Therapeutics Come of Age
Ingham, M. A., & Schwartz, G. K. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.69.0032 · Cited by 357 · see citing works
The Strange Case of CDK4/6 Inhibitors: Mechanisms, Resistance, and Combination Strategies
Knudsen, E. S., & Witkiewicz, A. K. (2017) · Trends in cancer · doi:10.1016/j.trecan.2016.11.006 · Cited by 285 · see citing works
Self-citationHafner, M., Mills, C. E., Subramanian, K., Chen, C., Chung, M., Boswell, S. A., Everley, R. A., Liu, C., Walmsley, C. S., Juric, D., et al. (2019) · Cell Chemical Biology · doi:10.1016/j.chembiol.2019.05.005 · Cited by 250 · see citing works
Pishvaian, M. J., Bender, R. J., Halverson, D., Rahib, L., Hendifar, A. E., Mikhail, S., Chung, V., Picozzi, V. J., Sohal, D., Blais, E. M., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0531 · Cited by 245 · see citing works
Cyclin D-CDK4/6 functions in cancer
Gao, X., Leone, G. W., & Wang, H. (2020) · Advances in cancer research · doi:10.1016/bs.acr.2020.02.002 · Cited by 220 · see citing works
Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer
Zhang, H., Pandey, S., Travers, M. E., Sun, H., Morton, G. C., Madžo, J., Chung, W., Khowsathit, J., Pérez, Ó. C., Barrero, C. A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.051 · Cited by 218 · see citing works
Franco, J., Balaji, U., Freinkman, E., Witkiewicz, A. K., & Knudsen, E. S. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.094 · Cited by 199 · see citing works
Self-citationCell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy
Knudsen, E. S., Pruitt, S. C., Hershberger, P. A., Witkiewicz, A. K., & Goodrich, D. W. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.03.005 · Cited by 185 · see citing works
Self-citationCDK4/6 Inhibitors Impair Recovery from Cytotoxic Chemotherapy in Pancreatic Adenocarcinoma
Salvador-Barberó, B., Álvarez‐Fernández, M., Zapatero‐Solana, E., Bakkali, A. E., Menéndez, C., Lopez-Casas, P. P., Domenico, T. D., Xie, T., VanArsdale, T. L., Shields, D. J., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.01.007 · Cited by 176 · see citing works
Rapid adaptation to CDK2 inhibition exposes intrinsic cell-cycle plasticity
Arora, M., Moser, J. C., Hoffman, T. E., Watts, L. P., Min, M., Musteanu, M., Rong, Y., Ill, C. R., Nangia, V., Schneider, J., et al. (2023) · Cell · doi:10.1016/j.cell.2023.05.013 · Cited by 170 · see citing works
Combination Therapies with CDK4/6 Inhibitors to Treat <i>KRAS-</i> Mutant Pancreatic Cancer
Goodwin, C. M., Waters, A. M., Klomp, J. E., Javaid, S., Bryant, K. L., Stalnecker, C. A., Drizyte-Miller, K., Papke, B., Yang, R., Amparo, A. M., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-0391 · Cited by 168 · see citing works
Targeting CDK6 in cancer: State of the art and new insights
Tadesse, S., Yu, M., Kumarasiri, M., Le, B. T., & Wang, S. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1084445 · Cited by 166 · see citing works
Overcoming CDK4/6 inhibitor resistance in ER-positive breast cancer
Portman, N., Alexandrou, S., Carson, E., Wang, S., Lim, E., & Caldon, C. E. (2018) · Endocrine Related Cancer · doi:10.1530/erc-18-0317 · Cited by 161 · see citing works
Development of Chemotherapy with Cell-Cycle Inhibitors for Adult and Pediatric Cancer Therapy
Mills, C. C., Kolb, E. A., & Sampson, V. B. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2782 · Cited by 152 · see citing works
Kovatcheva, M., Liu, D. D., Dickson, M. A., Klein, M. E., O’Connor, R., Wilder, F. O., Socci, N. D., Tap, W. D., Schwartz, G. K., Singer, S., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3364 · Cited by 142 · see citing works
Prospects of targeting PI3K/AKT/mTOR pathway in pancreatic cancer
Mortazavi, M., Moosavi, F., Martini, M., Giovannetti, E., & Firuzi, O. (2022) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2022.103749 · Cited by 126 · see citing works
Synergistic Drug Combinations with a CDK4/6 Inhibitor in T-cell Acute Lymphoblastic Leukemia
Pikman, Y., Alexe, G., Roti, G., Conway, A. S., Furman, A. A., Lee, E. S., Place, A. E., Kim, S., Saran, C., Modiste, R., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2869 · Cited by 112 · see citing works
Genetic Diversity of Pancreatic Ductal Adenocarcinoma and Opportunities for Precision Medicine
Knudsen, E. S., O'Reilly, E. M., Brody, J. R., & Witkiewicz, A. K. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.08.056 · Cited by 108 · see citing works
Self-citationCombined CDK4/6 and mTOR Inhibition Is Synergistic against Glioblastoma via Multiple Mechanisms
Olmez, I., Brenneman, B. R., Xiao, A., Serbulea, V., Benamar, M., Zhang, Y., Manigat, L. C., Abbas, T., Lee, J., Nakano, I., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0803 · Cited by 107 · see citing works
Targeting PI3K signaling in cancer: Challenges and advances
Santis, M. C. D., Gulluni, F., Campa, C. C., Martini, M., & Hirsch, E. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.03.003 · Cited by 105 · see citing works
Pack, L. R., Daigh, L. H., Chung, M., & Meyer, T. (2021) · Nature Communications · doi:10.1038/s41467-021-23612-z · Cited by 98 · see citing works
Therapeutic Strategies for Targeting CDKN2A Loss in Melanoma
Kreuger, I. Z. M., Slieker, R. C., van Groningen, T., & van Doorn, R. (2022) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2022.07.016 · Cited by 97 · see citing works
Al Baghdadi, T., Halabi, S., Garrett-Mayer, E., Mangat, P. K., Ahn, E. R., Sahai, V., Alvarez, R. H., Kim, E. S., Yost, K. J., Rygiel, A. L., et al. (2019) · JCO Precision Oncology · doi:10.1200/po.19.00124 · Cited by 94 · see citing works
Al-Qasem, A. J., Alves, C. L., Ehmsen, S., Tuttolomondo, M., Terp, M. G., Johansen, L. E., Vever, H., Hoeg, L. V. A., Eliáš, D., Bak, M., et al. (2022) · npj Precision Oncology · doi:10.1038/s41698-022-00311-6 · Cited by 92 · see citing works
New therapeutic targets in pancreatic cancer
Lai, E., Puzzoni, M., Ziranu, P., Pretta, A., Impera, V., Mariani, S., Liscia, N., Soro, P., Musio, F., Persano, M., et al. (2019) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2019.101926 · Cited by 91 · see citing works
The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma
García-Reyes, B., Kretz, A.-L., Ruff, J.-P., von Karstedt, S., Hillenbrand, A., Knippschild, U., Henne‐Bruns, D., & Lemke, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103219 · Cited by 90 · see citing works
Wang, J., Li, Q., Yuan, J., Wang, J., Chen, Z., Liu, Z., Li, Z., Lai, Y., Gao, J., & Shen, L. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1231-7 · Cited by 84 · see citing works
Preclinical Therapeutic Synergy of MEK1/2 and CDK4/6 Inhibition in Neuroblastoma
Hart, L. S., Rader, J., Raman, P., Batra, V., Russell, M. R., Tsang, M., Gagliardi, M. E., Chen, L. L., Martínez, D., Li, Y., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1131 · Cited by 81 · see citing works
Knudsen, E. S., Kumarasamy, V. M., Chung, S., Ruiz, A., Vail, P. J., Tzetzo, S. L., Wu, J., Nambiar, R., Sivinski, J., Chauhan, S. S., et al. (2020) · Gut · doi:10.1136/gutjnl-2020-321000 · Cited by 81 · see citing works
Self-citationCDK4/6 inhibitors in breast cancer therapy: Current practice and future opportunities
Lynce, F. C., Shajahan‐Haq, A. N., & Swain, S. M. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.06.008 · Cited by 78 · see citing works
Hutcheson, J., Balaji, U., Porembka, M. R., Wachsmann, M., McCue, P. A., Knudsen, E. S., & Witkiewicz, A. K. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1883 · Cited by 75 · see citing works
Self-citationMechanisms of CDK4/6 Inhibitor Resistance in Luminal Breast Cancer
Li, Z., Zou, W., Zhang, J., Zhang, Y., Xu, Q., Li, S., & Chen, C. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.580251 · Cited by 73 · see citing works
The Renaissance of Cyclin Dependent Kinase Inhibitors
Ettl, T., Schulz, D., & Bauer, R. J. (2022) · Cancers · doi:10.3390/cancers14020293 · Cited by 71 · see citing works
CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review
Vinciguerra, G. L. R., Sonego, M., Segatto, I., Dall’Acqua, A., Vecchione, A. M., Baldassarre, G., & Belletti, B. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.891580 · Cited by 71 · see citing works
Estrada‐Bernal, A., Chatterjee, M., Haque, S. J., Yang, L., Morgan, M. A., Kotian, S., Morrell, D., Chakravarti, A., & Williams, T. M. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1104437 · Cited by 70 · see citing works
Ji, Y. C., Liu, X., Li, J., Xie, X., Huang, M. T.-H., Jiang, J., Liao, Y., Donahue, T. R., & Meng, H. (2020) · Nature Communications · doi:10.1038/s41467-020-17996-7 · Cited by 68 · see citing works
The Role of Inherited Pathogenic CDKN2A Variants in Susceptibility to Pancreatic Cancer
Kimura, H., Klein, A. P., Hruban, R. H., & Roberts, N. J. (2021) · Pancreas · doi:10.1097/mpa.0000000000001888 · Cited by 65 · see citing works
Molecular Events in the Natural History of Pancreatic Cancer
Oldfield, L. E., Connor, A. A., & Gallinger, S. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.04.005 · Cited by 65 · see citing works
Knudsen, E. S., Kumarasamy, V. M., Ruiz, A., Sivinski, J., Chung, S., Grant, A. D., Vail, P. J., Chauhan, S. S., Jie, T., Riall, T. S., et al. (2019) · Oncogene · doi:10.1038/s41388-018-0650-0 · Cited by 64 · see citing works
Self-citationCombined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma
Olmez, I., Zhang, Y., Manigat, L. C., Benamar, M., Brenneman, B. R., Nakano, I., Godlewski, J. A., Bronisz, A., Lee, J., Abbas, T., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-3124 · Cited by 63 · see citing works
Resistance mechanisms and therapeutic strategies of CDK4 and CDK6 kinase targeting in cancer
Asciolla, J. J., Wu, X., Adamopoulos, C., Gavathiotis, E., & Poulikakos, P. I. (2025) · Nature Cancer · doi:10.1038/s43018-024-00893-z · Cited by 62 · see citing works
Efficacy of CDK4 inhibition against sarcomas depends on their levels of CDK4 and p16ink4 mRNA
Pérez, M., Muñoz-Galván, S., Jiménez-García, M. P., Marín, J., & Carnero, A. (2015) · Oncotarget · doi:10.18632/oncotarget.5829 · Cited by 62 · see citing works
Bisi, J., Sorrentino, J. A., Jordan, J. L., Darr, D. D., Roberts, P. J., Tavares, F. X., & Strum, J. C. (2017) · Oncotarget · doi:10.18632/oncotarget.16216 · Cited by 62 · see citing works
Novel Molecular Markers for Breast Cancer
Inoue, K., & Fry, E. A. (2016) · Biomarkers in Cancer · doi:10.4137/bic.s38394 · Cited by 61 · see citing works
Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows
Roberts, P. J., Kumarasamy, V. M., Witkiewicz, A. K., & Knudsen, E. S. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1161 · Cited by 60 · see citing works
Self-citationYamamoto, T., Kanaya, N., Somlo, G., & Chen, S. (2019) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-05104-9 · Cited by 60 · see citing works
Ku, B. M., Yi, S. Y., Koh, J., Bae, Y.-H., Sun, J., Lee, S., Ahn, J. S., Park, K., & Ahn, M. (2016) · Oncotarget · doi:10.18632/oncotarget.7543 · Cited by 57 · see citing works
Abemaciclib Is Effective Against Pancreatic Cancer Cells and Synergizes with HuR and YAP1 Inhibition
Dhir, T., Schultz, C. W., Jain, A., Brown, S. Z., Haber, A. O., Goetz, A. B., Xi, C., Su, G. H., Xu, L., Posey, J. A., et al. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0589 · Cited by 57 · see citing works
Selective impact of CDK4/6 suppression on patient-derived models of pancreatic cancer
Witkiewicz, A. K., Borja, N. A., Franco, J., Brody, J. R., Yeo, C. J., Mansour, J., Choti, M. A., McCue, P., & Knudsen, E. S. (2015) · Oncotarget · doi:10.18632/oncotarget.3819 · Cited by 56 · see citing works
Self-citationFunctional Genomic Analysis of CDK4 and CDK6 Gene Dependency across Human Cancer Cell Lines
Zhang, Z., Golomb, L., & Meyerson, M. M. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-2428 · Cited by 56 · see citing works
Robinson, A. M., Rathore, R., Redlich, N. J., Adkins, D. R., VanArsdale, T. L., Tine, B. A. V., & Michel, L. S. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-2098-8 · Cited by 56 · see citing works
Haines, E., Chen, T., Kommajosyula, N., Chen, Z., Herter-Sprie, G. S., Cornell, L., Wong, K., & Shapiro, G. I. (2018) · Oncotarget · doi:10.18632/oncotarget.25803 · Cited by 53 · see citing works
Gopalan, P. K., Villegas, A. G., Cao, C., Pinder-Schenck, M. C., Chiappori, A., Hou, W., Zajac‐Kaye, M., Ivey, A. M., & Kaye, F. J. (2018) · Oncotarget · doi:10.18632/oncotarget.26424 · Cited by 49 · see citing works
Germline Variants and Risk for Pancreatic Cancer
Zhan, W., Shelton, C. A., Greer, P. J., Brand, R. E., & Whitcomb, D. C. (2018) · Pancreas · doi:10.1097/mpa.0000000000001136 · Cited by 48 · see citing works
Zhang, J., Zhou, L., Zhao, S., Dicker, D. T., & El‐Deiry, W. S. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1320005 · Cited by 47 · see citing works
Kong, T., Xue, Y., Cencic, R., Zhu, X., Monast, A., Fu, Z., Pilon, V., Sangwan, V., Guiot, M., Foulkes, W. D., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0162 · Cited by 46 · see citing works
Small Molecule CDK Inhibitors for the Therapeutic Management of Cancer
Goel, B., Tripathi, N., Bhardwaj, N., & Jain, S. K. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200516152756 · Cited by 45 · see citing works
Pan, Z., Chen, Y., Liu, J., Jiang, Q., Yang, S., Guo, L., & He, G. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.12.046 · Cited by 43 · see citing works
Feng, W. W., & Kurokawa, M. (2019) · Cancer Drug Resistance · doi:10.20517/cdr.2019.100 · Cited by 43 · see citing works
Rational drug combinations with CDK4/6 inhibitors in acute lymphoblastic leukemia
Bride, K. L., Hu, H., Tikhonova, A. N., Fuller, T. J., Vincent, T. L., Shraim, R., Li, M. M., Carroll, W. L., Raetz, E. A., Aifantis, I., et al. (2021) · Haematologica · doi:10.3324/haematol.2021.279410 · Cited by 43 · see citing works
Willobee, B., Gaidarski, A. A., Dosch, A., Castellanos, J. A., Dai, X., Mehra, S., Messaggio, F., Srinivasan, S., VanSaun, M. N., Nagathihalli, N. S., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-1043 · Cited by 24 · see citing works
Recent advances in drug delivery and targeting for the treatment of pancreatic cancer
Pramanik, N., Gupta, A. K., Ghanwatkar, Y., & Mahato, R. I. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.12.053 · Cited by 42 · see citing works
CDK4/6 inhibitors in P16/HPV16-negative squamous cell carcinoma of the head and neck
Billard-Sandu, C., Tao, Y., Sablin, M., Dumitrescu, G., Billard, D., & Deutsch, É. (2020) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-020-05891-2 · Cited by 42 · see citing works
Adamopoulos, C., Cave, D. D., & Papavassiliou, A. G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031631 · Cited by 41 · see citing works
Mutation matters in precision medicine: A future to believe in
Dey, N., Williams, C. B., Leyland-Jones, B. R., & De, P. K. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.03.002 · Cited by 41 · see citing works
Pan‐cancer RNA‐seq data stratifies tumours by some hallmarks of cancer
Frost, F. G., Cherukuri, P. F., Milanovich, S. J., & Boerkoel, C. F. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14746 · Cited by 41 · see citing works
CDK4 inhibition diminishes p53 activation by MDM2 antagonists
Sriraman, A., Dickmanns, A., Najafova, Z., Johnsen, S. A., & Dobbelstein, M. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0968-0 · Cited by 40 · see citing works
CDKN2AGermline Rare Coding Variants and Risk of Pancreatic Cancer in Minority Populations
McWilliams, R. R., Wieben, E. D., Rabe, K. G., Antwi, S. O., Raskin, L., Olopade, O. I., Li, D., Highsmith, W. E., Colón‐Otero, G., Khanna, L. G., et al. (2018) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-17-1065 · Cited by 40 · see citing works
Nur, S. Z., Bernard, K. B. L., Zheng, W. W., Iuan, S. C., Pei, S. Y., Gan, C. P., Kein, S. M., Zainal, A. A. R., Gutkind, J. S., Vyomesh, P., et al. (2019) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2018.0257 · Cited by 40 · see citing works
Mahale, S., Bharate, S. B., Manda, S., Joshi, P., Bharate, S. S., Jenkins, P. R., Vishwakarma, R. A., & Chaudhuri, B. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5014743 · Cited by 39 · see citing works
Cui, D., Zhao, Y., & Xu, J. (2018) · Cancer Biology & Therapy · doi:10.1080/15384047.2018.1539289 · Cited by 38 · see citing works
Kumarasamy, V. M., Ruiz, A., Nambiar, R., Witkiewicz, A. K., & Knudsen, E. S. (2019) · Oncogene · doi:10.1038/s41388-019-1102-1 · Cited by 39 · see citing works
Self-citationZhang, C., Stockwell, S. R., Elbanna, M., Ketteler, R., Freeman, J., Al‐Lazikani, B., Eccles, S. A., Brandon, A. D. H., Raynaud, F. I., Hayes, A., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0850-2 · Cited by 37 · see citing works
Knudsen, E. S., Shapiro, G. I., & Keyomarsi, K. (2020) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_281085 · Cited by 36 · see citing works
Self-citationDelving into Early-onset Pancreatic Ductal Adenocarcinoma: How Does Age Fit In?
Tsang, E. S., Topham, J. T., Karasinska, J. M., Lee, M. K. C., Williamson, L., Mendis, S. R., Denroche, R. E., Jang, G. H., Kalloger, S. E., Moore, R. A., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-1042 · Cited by 36 · see citing works
Yousuf, M., Alam, M., Shamsi, A., Κhan, P., Hasan, G. M., Haque, Q. M. R., & Hassan, M. I. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.07.156 · Cited by 36 · see citing works
Awasthi, N., Monahan, S., Stefaniak, A., Schwarz, M. A., & Schwarz, R. E. (2017) · Oncotarget · doi:10.18632/oncotarget.23684 · Cited by 35 · see citing works
Digiacomo, G., Fumarola, C., Monica, S. L., Bonelli, M. A., Cretella, D., Alfieri, R. R., Cavazzoni, A., Galetti, M., Bertolini, P., Missale, G., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.563249 · Cited by 35 · see citing works
Macchini, M., Centonze, F., Peretti, U., Orsi, G., Militello, A. M., Valente, M. M., Cascinu, S., & Reni, M. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102262 · Cited by 33 · see citing works
Asby, D. J., Killick-Cole, C. L., Boulter, L. J., Singleton, W., Asby, C., Wyatt, M. J., Barua, N. U., Bienemann, A. S., & Gill, S. (2018) · Cancer Management and Research · doi:10.2147/cmar.s167095 · Cited by 32 · see citing works
Sante, G. D., Pagé, J., Jiao, X., Nawab, O., Cristofanilli, M., Skordalakes, E., & Pestell, R. G. (2019) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2019.1615889 · Cited by 32 · see citing works
High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells
Horn, T. L., Ferretti, S., Ebel, N., Tam, A., Ho, S. B., Harbinski, F., Farsidjani, A., Zubrowski, M. J., Sellers, W. R., Schlegel, R., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3425 · Cited by 32 · see citing works
Beyond cell cycle regulation: The pleiotropic function of CDK4 in cancer
Ziegler, D. V., Parashar, K., & Lluis Fajas, A. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.12.002 · Cited by 30 · see citing works
Dihydroartemisinin suppresses pancreatic cancer cells via a microRNA-mRNA regulatory network
Li, Y., Wang, Y., Kong, R., Xue, D., Pan, S., Chen, H., & Sun, B. (2016) · Oncotarget · doi:10.18632/oncotarget.11517 · Cited by 30 · see citing works
FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors
Briest, F., Berg, E. G., Grass, I., Freitag, H., Kaemmerer, D., Lewens, F., Christen, F., Arsenić, R., Altendorf-Hofmann, A., Kunze, A., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3600 · Cited by 29 · see citing works
Knudsen, E. S., & Witkiewicz, A. K. (2016) · Oncotarget · doi:10.18632/oncotarget.11588 · Cited by 29 · see citing works
Self-citationCombined inhibition of ACLY and CDK4/6 reduces cancer cell growth and invasion
Velez, B. C., Petrella, C., DiSalvo, K. H., Cheng, K., Kravtsov, R. L., Krasniqi, D., & Krucher, N. A. (2022) · Oncology Reports · doi:10.3892/or.2022.8469 · Cited by 29 · see citing works
CDKN2A Gene Mutations: Implications for Hereditary Cancer Syndromes
Михайловна, Д. А., Bilyalov, A. I., Nikolaev, S., Khalikov, N., Isaeva, D., Levina, Y. G., Makarova, M. V., Nemtsova, M. V., Chernevskiy, D. K., Sagaydak, O. V., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11123343 · Cited by 28 · see citing works
- Authors
- Franco, J., Witkiewicz, A. K., & Knudsen, E. S.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Harold C. Simmons Comprehensive Cancer Center (US)
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2014-07-26
- Volume
- 5
- Issue
- 15
- Pages
- 6512-6525
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4171647
- OpenAlex
- W2118874870
- Cited by
- 207
- References
- 61
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 19 · 2022: 23 · 2021: 17 · 2020: 21 · 2019: 25 · 2018: 31 · 2017: 20 · 2016: 15 · 2015: 15 · 2014: 1
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- CDK4/6 inhibitors, pancreatic ductal adenocarcinoma, palbociclib, retinoblastoma protein, CDKN2A loss, E2F transcription factors, cyclin E1, drug resistance, combination therapy, PI3K/mTOR inhibitors, MEK inhibitors, taxanes, PLK1 inhibitors, 5-fluorouracil, gemcitabine, drug synergy, DNA replication
- MeSH terms
- Humans, Pancreatic Neoplasms, Piperazines, Prognosis, Pyridines, Transfection, Gene Expression, Cyclin-Dependent Kinase Inhibitor p16, Gene Expression Profiling, Carcinoma, Pancreatic Ductal, Cell Line, Tumor, Protein Kinase Inhibitors, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6
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
