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Therapeutic strategies for targeting ras proteins.
Gysin S, Salt M, Young A, McCormick F. Gysin S, et al. Among authors: young a. Genes Cancer. 2011 Mar;2(3):359-72. doi: 10.1177/1947601911412376. Genes Cancer. 2011. PMID: 21779505 Free PMC article.
This activation is mediated by EGF-R and other receptor tyrosine kinases through relief of a negative feedback loop from ERK. ...Other effectors may also contribute to Ras signaling and provide a source of targets. In addition, unbiased screens for genes necessary f …
This activation is mediated by EGF-R and other receptor tyrosine kinases through relief of a negative feedback loop from ERK. ...Othe …
Systems-wide analysis of K-Ras, Cdc42, and PAK4 signaling by quantitative phosphoproteomics.
Gnad F, Young A, Zhou W, Lyle K, Ong CC, Stokes MP, Silva JC, Belvin M, Friedman LS, Koeppen H, Minden A, Hoeflich KP. Gnad F, et al. Among authors: young a. Mol Cell Proteomics. 2013 Aug;12(8):2070-80. doi: 10.1074/mcp.M112.027052. Epub 2013 Apr 22. Mol Cell Proteomics. 2013. PMID: 23608596 Free PMC article.
Although K-Ras, Cdc42, and PAK4 signaling are commonly deregulated in cancer, only a few studies have sought to comprehensively examine the spectrum of phosphorylation-mediated signaling downstream of each of these key signaling nodes. ...These findings provide a re …
Although K-Ras, Cdc42, and PAK4 signaling are commonly deregulated in cancer, only a few studies have sought to comprehensively exami …
Oncogenic and wild-type Ras play divergent roles in the regulation of mitogen-activated protein kinase signaling.
Young A, Lou D, McCormick F. Young A, et al. Cancer Discov. 2013 Jan;3(1):112-23. doi: 10.1158/2159-8290.CD-12-0231. Epub 2012 Oct 25. Cancer Discov. 2013. PMID: 23103856
Although oncogenic lesions occur in a single Ras isoform within individual tumors, it is unclear whether the remaining wild-type isoforms play supporting roles in tumor growth. ...SIGNIFICANCE: The results of this study highlight a novel role for wild-type Ras signa …
Although oncogenic lesions occur in a single Ras isoform within individual tumors, it is unclear whether the remaining wild-type isof …
Ras signaling and therapies.
Young A, Lyons J, Miller AL, Phan VT, Alarcón IR, McCormick F. Young A, et al. Adv Cancer Res. 2009;102:1-17. doi: 10.1016/S0065-230X(09)02001-6. Adv Cancer Res. 2009. PMID: 19595305 Review.
In this time, it has been established beyond doubt that these mutations play a direct role in causing cancer, and do so in collaboration with a number of other oncogenes and tumor suppressors. ...
In this time, it has been established beyond doubt that these mutations play a direct role in causing cancer, and do so in collaborat …
KRAS Allelic Imbalance Enhances Fitness and Modulates MAP Kinase Dependence in Cancer.
Burgess MR, Hwang E, Mroue R, Bielski CM, Wandler AM, Huang BJ, Firestone AJ, Young A, Lacap JA, Crocker L, Asthana S, Davis EM, Xu J, Akagi K, Le Beau MM, Li Q, Haley B, Stokoe D, Sampath D, Taylor BS, Evangelista M, Shannon K. Burgess MR, et al. Among authors: young a. Cell. 2017 Feb 23;168(5):817-829.e15. doi: 10.1016/j.cell.2017.01.020. Epub 2017 Feb 16. Cell. 2017. PMID: 28215705 Free PMC article.
Similarly, human colorectal cancer cell lines with increased KRAS mutant allele frequency were more sensitive to MAP kinase inhibition, and CRISPR-Cas9-mediated replacement of WT KRAS with a mutant allele sensitized heterozygous mutant HCT116 cells to treatment. In a
Similarly, human colorectal cancer cell lines with increased KRAS mutant allele frequency were more sensitive to MAP kinase inhibition, and …
Expression Profile of BCL-2, BCL-XL, and MCL-1 Predicts Pharmacological Response to the BCL-2 Selective Antagonist Venetoclax in Multiple Myeloma Models.
Punnoose EA, Leverson JD, Peale F, Boghaert ER, Belmont LD, Tan N, Young A, Mitten M, Ingalla E, Darbonne WC, Oleksijew A, Tapang P, Yue P, Oeh J, Lee L, Maiga S, Fairbrother WJ, Amiot M, Souers AJ, Sampath D. Punnoose EA, et al. Among authors: young a. Mol Cancer Ther. 2016 May;15(5):1132-44. doi: 10.1158/1535-7163.MCT-15-0730. Epub 2016 Mar 3. Mol Cancer Ther. 2016. PMID: 26939706
Multiple myeloma cells that coexpress BCL-2 and BCL-XL were resistant to venetoclax but sensitive to a BCL-XL-selective inhibitor (A-1155463). ...In contrast, xenografts that expressed BCL-XL, MCL-1, and BCL-2 were more sensitive to the combination of bortezomib wit …
Multiple myeloma cells that coexpress BCL-2 and BCL-XL were resistant to venetoclax but sensitive to a BCL-XL-selective inhibitor ( …
Single-Cell Dynamics Determines Response to CDK4/6 Inhibition in Triple-Negative Breast Cancer.
Asghar US, Barr AR, Cutts R, Beaney M, Babina I, Sampath D, Giltnane J, Lacap JA, Crocker L, Young A, Pearson A, Herrera-Abreu MT, Bakal C, Turner NC. Asghar US, et al. Among authors: young a. Clin Cancer Res. 2017 Sep 15;23(18):5561-5572. doi: 10.1158/1078-0432.CCR-17-0369. Epub 2017 Jun 12. Clin Cancer Res. 2017. PMID: 28606920 Free PMC article.
Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer that is associated with a poor prognosis. ...Palbociclib-sensitive LAR cells exit mitosis with low levels of CDK2 activity, into a quiescent state that requires CDK4/6 …
Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer that is associated with a poor prog …
Phosphoproteomic characterization of DNA damage response in melanoma cells following MEK/PI3K dual inhibition.
Kirkpatrick DS, Bustos DJ, Dogan T, Chan J, Phu L, Young A, Friedman LS, Belvin M, Song Q, Bakalarski CE, Hoeflich KP. Kirkpatrick DS, et al. Among authors: young a. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19426-31. doi: 10.1073/pnas.1309473110. Epub 2013 Nov 11. Proc Natl Acad Sci U S A. 2013. PMID: 24218548 Free PMC article.
Upon treatment, melanoma cell lines responded by dramatically increasing phosphorylation on proteins containing a canonical DNA damage-response (DDR) motif, as defined by a phosphorylated serine or threonine residue adjacent to glutamine, [s/t]Q. ...Network analysis …
Upon treatment, melanoma cell lines responded by dramatically increasing phosphorylation on proteins containing a canonical DNA damag …
Role of the E3 ubiquitin ligase RNF157 as a novel downstream effector linking PI3K and MAPK signaling pathways to the cell cycle.
Dogan T, Gnad F, Chan J, Phu L, Young A, Chen MJ, Doll S, Stokes MP, Belvin M, Friedman LS, Kirkpatrick DS, Hoeflich KP, Hatzivassiliou G. Dogan T, et al. Among authors: young a. J Biol Chem. 2017 Sep 1;292(35):14311-14324. doi: 10.1074/jbc.M117.792754. Epub 2017 Jun 27. J Biol Chem. 2017. PMID: 28655764 Free PMC article.
Using mass spectrometry-based phosphoproteomics, we have identified the RING finger E3 ubiquitin ligase RNF157 as a target at the intersection of PI3K and MAPK signaling. ...We propose that RNF157 serves as a novel node integrating oncogenic signaling pathways with …
Using mass spectrometry-based phosphoproteomics, we have identified the RING finger E3 ubiquitin ligase RNF157 as a target at the int …
The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer.
Joseph JD, Darimont B, Zhou W, Arrazate A, Young A, Ingalla E, Walter K, Blake RA, Nonomiya J, Guan Z, Kategaya L, Govek SP, Lai AG, Kahraman M, Brigham D, Sensintaffar J, Lu N, Shao G, Qian J, Grillot K, Moon M, Prudente R, Bischoff E, Lee KJ, Bonnefous C, Douglas KL, Julien JD, Nagasawa JY, Aparicio A, Kaufman J, Haley B, Giltnane JM, Wertz IE, Lackner MR, Nannini MA, Sampath D, Schwarz L, Manning HC, Tantawy MN, Arteaga CL, Heyman RA, Rix PJ, Friedman L, Smith ND, Metcalfe C, Hager JH. Joseph JD, et al. Among authors: young a. Elife. 2016 Jul 13;5:e15828. doi: 10.7554/eLife.15828. Elife. 2016. PMID: 27410477 Free PMC article.
The recent discovery of prevalent ESR1 mutations in relapsed tumors underscores a sustained reliance of advanced tumors on ERα signaling, and provides a strong rationale for continued targeting of ERα. ...GDC-0810 induces a distinct ERα conformation, relative …
The recent discovery of prevalent ESR1 mutations in relapsed tumors underscores a sustained reliance of advanced tumors on ERα signal …
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