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Chapter 22 - Drugs, Genomic Response Signatures, and Customized Cancer Therapy

from Section five - Chemical Genomics and Medicine

Published online by Cambridge University Press:  05 June 2012

By
Rafael Rosell ,
Teresa Moran  and
Miguel Taron
Edited by
Haian Fu
Haian Fu
Affiliation:
Emory University, Atlanta
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Summary

Aberrant signaling generated by the activation of multiple pathways occurs in cancers and contributes to their growth, invasion, and survival. For example, lung cancer–specific epidermal growth factor receptor (EGFR) mutations result in constitutive activation of EGFR and downstream signaling components, such as Akt, with dramatic response to tyrosine kinase inhibitors (TKIs) (gefitinib or erlotinib). In patients with multiple metastases, a single pill of erlotinib daily can attain a 70% response rate, a twelve-month time to progression, and a twenty-two-month median survival. In fact, in some subgroups of patients, survival has not been reached. However, results can still be further improved. A growing body of evidence suggests a role for lateral signaling or cross talk between various receptor tyrosine kinases (TKs), with subsequent signaling through multiple receptors. This knowledge can facilitate the design of new therapeutic strategies. New data on the role of prognostic markers will help both to identify the high-risk group of patients who will relapse after surgery and to customize treatment for all patients. DNA damage response is a global signaling network that – among multiple functions – facilitates DNA repair processes and thus determines the sensitivity or resistance to different cytotoxic drugs. Central to DNA damage response is the breast cancer gene 1 (BRCA1). We have examined the predictive value of the BRCA1-RAP80-Abraxas complex in patients with metastatic lung cancer who were receiving customized treatment according to BRCA1 messenger RNA (mRNA) levels. Our results indicate that a subgroup of patients with low levels of BRCA1 and RAP80 respond dramatically to cisplatin-based chemotherapy, with a time to progression of fourteen months and median survival not reached. These clinical findings require additional validation but can be even further improved with the proper combination with targeted therapy based on identification of the right molecular targets. This model of customization can be extrapolated to multiple different primary tumors.

Type
Chapter
Information
Chemical Genomics , pp. 301 - 319
Publisher: Cambridge University Press
Print publication year: 2012

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References

Jemal, ASiegel, RWard, EHao, YXu, JMurray, TThun, M. J 2008 Cancer statistics, 2008CA Cancer J Clin 58 71Google Scholar
Jemal, ASiegel, RWard, EMurray, TXu, JThun, M. J 2007 Cancer statistics, 2007CA Cancer J Clin 57 43Google Scholar
Hanahan, DWeinberg, R. A 2000 The hallmarks of cancerCell 100 57Google Scholar
Huang, EIshida, SPittman, JDressman, HBild, AKloos, MD’Amico, MPestell, R. GWest, MNevins, J. R 2003 Gene expression phenotypic models that predict the activity of oncogenic pathwaysNat Genet 34 226Google Scholar
Vogelstein, BLane, DLevine, A. J 2000 Surfing the p53 networkNature 408 307Google Scholar
Downward, J 2003 Targeting RAS signalling pathways in cancer therapyNat Rev Cancer 3 11Google Scholar
Okada, FRak, J. WCroix, B. SLieubeau, BKaya, MRoncari, LShirasawa, SSasazuki, TKerbel, R. S 1998 Impact of oncogenes in tumor angiogenesis: mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cellsProc Natl Acad Sci U S A 95 3609Google Scholar
Yang, JMani, S. ADonaher, J. LRamaswamy, SItzykson, R. ACome, CSavagner, PGitelman, IRichardson, AWeinberg, R.A 2004 Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasisCell 117 927Google Scholar
Minn, A. JGupta, G. PSiegel, P. MBos, P. DShu, WGiri, D. DViale, AOlshen, A. BGerald, W. LMassague, J 2005 Genes that mediate breast cancer metastasis to lungNature 436 518Google Scholar
McMurray, H. RSampson, E. RCompitello, GKinsey, CNewman, LSmith, BChen, S. RKlebanov, LSalzman, PYakovlev, ALand, H 2008 Synergistic response to oncogenic mutations defines gene class critical to cancer phenotypeNature 453 1112Google Scholar
Giaccone, GHerbst, R. SManegold, CScagliotti, GRosell, RMiller, VNatale, R. BSchiller, J. HVon Pawel, JPluzanska, AGatzemeier, UGrous, JOchs, J. SAverbuch, S. DWolf, M. KRennie, PFandi, AJohnson, D. H 2004 Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial – INTACT 1J Clin Oncol 22 777Google Scholar
Herbst, R. SGiaccone, GSchiller, J. HNatale, R. BMiller, VManegold, CScagliotti, GRosell, ROliff, IReeves, J. AWolf, M. KKrebs, A. DAverbuch, S. DOchs, J. SGrous, JFandi, AJohnson, D. H 2004 Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial – INTACT 2J Clin Oncol 22 785Google Scholar
Gatzemeier, UPluzanska, ASzczesna, AKaukel, ERoubec, JDe Rosa, FMilanowski, JKarnicka-Mlodkowski, HPesek, MSerwatowski, PRamlau, RJanaskova, TVansteenkiste, JStrausz, JManikhas, G. MVon Pawel, J 2007 Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation TrialJ Clin Oncol 25 1545Google Scholar
Wheatley-Price, PShepherd, F. A 2008 Epidermal growth factor receptor inhibitors in the treatment of lung cancer: reality and hopesCurr Opin Oncol 20 162Google Scholar
Bergers, GHanahan, D 2008 Modes of resistance to anti-angiogenic therapyNat Rev Cancer 8 592Google Scholar
Ellis, L. MHicklin, D. J 2008 VEGF-targeted therapy: mechanisms of anti-tumour activityNat Rev Cancer 8 579Google Scholar
Hurwitz, HFehrenbacher, LNovotny, WCartwright, THainsworth, JHeim, WBerlin, JBaron, AGriffing, SHolmgren, EFerrara, NFyfe, GRogers, BRoss, RKabbinavar, F 2004 Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancerN Engl J Med 350 2335Google Scholar
Sandler, AGray, RPerry, M. CBrahmer, JSchiller, J. HDowlati, ALilenbaum, RJohnson, D. H 2006 Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancerN Engl J Med 355 2542Google Scholar
Hoang, TXu, RSchiller, J. HBonomi, PJohnson, D. H 2005 Clinical model to predict survival in chemonaive patients with advanced non-small-cell lung cancer treated with third-generation chemotherapy regimens based on eastern cooperative oncology group dataJ Clin Oncol 23 175Google Scholar
Miller, KWang, MGralow, JDickler, MCobleigh, MPerez, E. AShenkier, TCella, DDavidson, N. E 2007 Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancerN Engl J Med 357 2666Google Scholar
Michaelson, M. DIliopoulos, OMcDermott, D. FMcGovern, F. JHarisinghani, M. GOliva, E 2008 Case records of the Massachusetts General Hospital. Case 17–2008. A 63-year-old man with metastatic renal-cell carcinomaN Engl J Med 358 2389Google Scholar
Skrzypski, MJassem, ETaron, MSanchez, J. JMendez, PRzyman, WGulida, GRaz, DJablons, DProvencio, MMassuti, BChaib, IPerez-Roca, LJassem, JRosell, R 2008 Three-gene expression signature predicts survival in early-stage squamous cell carcinoma of the lungClin Cancer Res 14 4794Google Scholar
Chang, H. YSneddon, J. BAlizadeh, A. ASood, RWest, R. BMontgomery, KChi, J. Tvan de Rijn, MBotstein, DBrown, P. O 2004 Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and woundsPLoS Biol 2Google Scholar
Massague, J 2007 Sorting out breast-cancer gene signaturesN Engl J Med 356 294Google Scholar
Rosell, RTaron, MJablons, D 2011 Lung cancer metastasisCancer Metastasis: Biologic Basis and TherapeuticsWelch, D. RLyden, D. CPsaila, BNew YorkCambridge University Press
Cai, SHan, H. JKohwi-Shigematsu, T 2003 Tissue-specific nuclear architecture and gene expression regulated by SATB1Nat Genet 34 42Google Scholar
Yasui, DMiyano, MCai, SVarga-Weisz, PKohwi-Shigematsu, T 2002 SATB1 targets chromatin remodelling to regulate genes over long distancesNature 419 641Google Scholar
Han, H. JRusso, JKohwi, YKohwi-Shigematsu, T 2008 SATB1 reprogrammes gene expression to promote breast tumour growth and metastasisNature 452 187Google Scholar
Kang, YSiegel, P. MShu, WDrobnjak, MKakonen, S. MCordon-Cardo, CGuise, T. AMassague, J 2003 A multigenic program mediating breast cancer metastasis to boneCancer Cell 3 537Google Scholar
Leary, AJohnston, S. R 2007 Small molecule signal transduction inhibitors for the treatment of solid tumorsCancer Invest 25 347Google Scholar
Roberts, P. JDer, C. J 2007 Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancerOncogene 26 3291Google Scholar
Solit, D. BGarraway, L. APratilas, C. ASawai, AGetz, GBasso, AYe, QLobo, J. MShe, YOsman, IGolub, T. RSebolt-Leopold, JSellers, W. RRosen, N 2006 BRAF mutation predicts sensitivity to MEK inhibitionNature 439 358Google Scholar
Dumaz, NHayward, RMartin, JOgilvie, LHedley, DCurtin, J. ABastian, B. CSpringer, CMarais, R 2006 In melanoma, RAS mutations are accompanied by switching signaling from BRAF to CRAF and disrupted cyclic AMP signalingCancer Res 66 9483Google Scholar
Montagut, CSharma, S. VShioda, TMcDermott, UUlman, MUlkus, L. EDias-Santagata, DStubbs, HLee, D. YSingh, ADrew, LHaber, D. ASettleman, J 2008 Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanomaCancer Res 68 4853Google Scholar
Amos, C. IWu, XBroderick, PGorlov, I. PGu, JEisen, TDong, QZhang, QGu, XVijayakrishnan, JSullivan, KMatakidou, AWang, YMills, GDoheny, KTsai, Y. YChen, W. VShete, SSpitz, M. RHoulston, R. S 2008 Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1Nat Genet 40 616Google Scholar
Hung, R. JMcKay, J. DGaborieau, VBoffetta, PHashibe, MZaridze, DMukeria, ASzeszenia-Dabrowska, NLissowska, JRudnai, PFabianova, EMates, DBencko, VForetova, LJanout, VChen, CGoodman, GField, J. KLiloglou, TXinarianos, GCassidy, AMcLaughlin, JLiu, GNarod, SKrokan, H. ESkorpen, FElvestad, M. BHveem, KVatten, LLinseisen, JClavel-Chapelon, FVineis, PBueno-de-Mesquita, H. BLund, EMartinez, CBingham, SRasmuson, THainaut, PRiboli, EAhrens, WBenhamou, SLagiou, PTrichopoulos, DHolcatova, IMerletti, FKjaerheim, KAgudo, AMacfarlane, GTalamini, RSimonato, LLowry, RConway, D. IZnaor, AHealy, CZelenika, DBoland, ADelepine, MFoglio, MLechner, DMatsuda, FBlanche, HGut, IHeath, SLathrop, MBrennan, P 2008 A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25Nature 452 633Google Scholar
Thorgeirsson, T. EGeller, FSulem, PRafnar, TWiste, AMagnusson, K. PManolescu, AThorleifsson, GStefansson, HIngason, AStacey, S. NBergthorsson, J. TThorlacius, SGudmundsson, JJonsson, TJakobsdottir, MSaemundsdottir, JOlafsdottir, OGudmundsson, L. JBjornsdottir, GKristjansson, KSkuladottir, HIsaksson, H. JGudbjartsson, TJones, G. TMueller, TGottsater, AFlex, AAben, K. Kde Vegt, FMulders, P. FIsla, DVidal, M. JAsin, LSaez, BMurillo, LBlondal, TKolbeinsson, HStefansson, J. GHansdottir, IRunarsdottir, VPola, RLindblad, Bvan Rij, A. MDieplinger, BHaltmayer, MMayordomo, J. IKiemeney, L. AMatthiasson, S. EOskarsson, HTyrfingsson, TGudbjartsson, D. FGulcher, J. RJonsson, SThorsteinsdottir, UKong, AStefansson, K 2008 A variant associated with nicotine dependence, lung cancer and peripheral arterial diseaseNature 452 638Google Scholar
Lam, D. CGirard, LRamirez, RChau, W. SSuen, W. SSheridan, STin, V. PChung, L. PWong, M. PShay, J. WGazdar, A. FLam, W. KMinna, J. D 2007 Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokersCancer Res 67 4638Google Scholar
Song, PSekhon, H. SFu, X. WMaier, MJia, YDuan, JProskosil, B. JGravett, CLindstrom, JMark, G. PSaha, SSpindel, E. R 2008 Activated cholinergic signaling provides a target in squamous cell lung carcinomaCancer Res 68 4693Google Scholar
Song, PSekhon, H. SLu, AArredondo, JSauer, DGravett, CMark, G. PGrando, S. ASpindel, E. R 2007 M3 muscarinic receptor antagonists inhibit small cell lung carcinoma growth and mitogen-activated protein kinase phosphorylation induced by acetylcholine secretionCancer Res 67 3936Google Scholar
Salomoni, PPandolfi, P. P 2002 The role of PML in tumor suppressionCell 108 165Google Scholar
Gurrieri, CCapodieci, PBernardi, RScaglioni, P. PNafa, KRush, L. JVerbel, D. ACordon-Cardo, CPandolfi, P. P 2004 Loss of the tumor suppressor PML in human cancers of multiple histologic originsJ Natl Cancer Inst 96 269Google Scholar
Daniels, M. JMarson, AVenkitaraman, A. R 2004 PML bodies control the nuclear dynamics and function of the CHFR mitotic checkpoint proteinNat Struct Mol Biol 11 1114Google Scholar
Wang, Z. GRuggero, DRonchetti, SZhong, SGaboli, MRivi, RPandolfi, P. P 1998 PML is essential for multiple apoptotic pathwaysNat Genet 20 266Google Scholar
Bernardi, RGuernah, IJin, DGrisendi, SAlimonti, ATeruya-Feldstein, JCordon-Cardo, CSimon, M. CRafii, SPandolfi, P. P 2006 PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTORNature 442 779Google Scholar
Faivre, SKroemer, GRaymond, E 2006 Current development of mTOR inhibitors as anticancer agentsNat Rev Drug Discov 5 671Google Scholar
Schewe, D. MAguirre-Ghiso, J. A 2008 ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivoProc Natl Acad Sci U S A 105 10519Google Scholar
Scaglioni, P. PYung, T. MCai, L. FErdjument-Bromage, HKaufman, A. JSingh, BTeruya-Feldstein, JTempst, PPandolfi, P. P 2006 A -dependent mechanism for degradation of the PML tumor suppressorCell 126 269Google Scholar
O-charoenrat, PRusch, VTalbot, S. GSarkaria, IViale, ASocci, NNgai, IRao, PSingh, B 2004 Casein kinase II alpha subunit and C1-inhibitor are independent predictors of outcome in patients with squamous cell carcinoma of the lungClin Cancer Res 10 5792Google Scholar
Shaw, R. JCantley, L. C 2006 Ras, PI(3)K and mTOR signalling controls tumour cell growthNature 441 424Google Scholar
Ayoub, NJeyasekharan, A. DBernal, J. AVenkitaraman, A. R 2008 HP1-beta mobilization promotes chromatin changes that initiate the DNA damage responseNature 453 682Google Scholar
Ito, KBernardi, RMorotti, AMatsuoka, SSaglio, GIkeda, YRosenblatt, JAvigan, D. ETeruya-Feldstein, JPandolfi, P. P 2008 PML targeting eradicates quiescent leukaemia-initiating cellsNature 453 1072Google Scholar
Su, T. T 2006 Cellular responses to DNA damage: one signal, multiple choicesAnnu Rev Genet 40 187Google Scholar
Bristow, R. GHill, R. P 2008 Hypoxia and metabolism. Hypoxia, DNA repair and genetic instabilityNat Rev Cancer 8 180Google Scholar
Halazonetis, T. DGorgoulis, V. GBartek, J 2008 An oncogene-induced DNA damage model for cancer developmentScience 319 1352Google Scholar
Harper, J. WElledge, S. J 2007 The DNA damage response: ten years afterMol Cell 28 739Google Scholar
Matsuoka, SBallif, B. ASmogorzewska, AMcDonald, E. RHurov, K. ELuo, JBakalarski, C. EZhao, ZSolimini, NLerenthal, YShiloh, YGygi, S. PElledge, S. J 2007 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damageScience 316 1160Google Scholar
Wang, BMatsuoka, SBallif, B. AZhang, DSmogorzewska, AGygi, S. PElledge, S. J 2007 Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage responseScience 316 1194Google Scholar
O’Connell, B. CHarper, J. W 2007 Ubiquitin proteasome system (UPS): what can chromatin do for you?Curr Opin Cell Biol 19 206Google Scholar
Guerrero-Santoro, JKapetanaki, M. GHsieh, C. LGorbachinsky, ILevine, A. SRapic-Otrin, V 2008 Cancer Res 68 5014
Sugasawa, K 2008 Xeroderma pigmentosum genes: functions inside and outside DNA repairCarcinogenesis 29 455Google Scholar
Adler, A. SLin, MHorlings, HNuyten, D. Svan de Vijver, M. JChang, H. Y 2006 Genetic regulators of large-scale transcriptional signatures in cancerNat Genet 38 421Google Scholar
Lue, HThiele, MFranz, JDahl, ESpeckgens, SLeng, LFingerle-Rowson, GBucala, RLuscher, BBernhagen, J 2007 Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activityOncogene 26 5046Google Scholar
Adler, A. SLittlepage, L. ELin, MKawahara, T. LWong, D. JWerb, ZChang, H. Y 2008 CSN5 isopeptidase activity links COP9 signalosome activation to breast cancer progressionCancer Res 68 506Google Scholar
Lue, HKapurniotu, AFingerle-Rowson, GRoger, TLeng, LThiele, MCalandra, TBucala, RBernhagen, J 2006 Rapid and transient activation of the ERK MAPK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on JAB1/CSN5 and Src kinase activityCell Signal 18 688Google Scholar
Wong, D. JNuyten, D. SRegev, ALin, MAdler, A. SSegal, Evan de Vijver, M. JChang, H. Y 2008 Revealing targeted therapy for human cancer by gene module mapsCancer Res 68 369Google Scholar
Tan, T. TDegenhardt, KNelson, D. ABeaudoin, BNieves-Neira, WBouillet, PVillunger, AAdams, J. MWhite, E 2005 Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapyCancer Cell 7 227Google Scholar
Welcker, MClurman, B. E 2008 FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiationNat Rev Cancer 8 83Google Scholar
Akhoondi, SSun, Dvon der Lehr, NApostolidou, SKlotz, KMaljukova, ACepeda, DFiegl, HDafou, DMarth, CMueller-Holzner, ECorcoran, MDagnell, MNejad, S. ZNayer, B. NZali, M. RHansson, JEgyhazi, SPetersson, FSangfelt, PNordgren, HGrander, DReed, S. IWidschwendter, MSangfelt, OSpruck, C 2007 FBXW7/hCDC4 is a general tumor suppressor in human cancerCancer Res 67 9006Google Scholar
Deeb, K. KMichalowska, A. MYoon, C. YKrummey, S. MHoenerhoff, M. JKavanaugh, CLi, M. CDemayo, F. JLinnoila, IDeng, C. XLee, E. YMedina, DShih, J. HGreen, J. E 2007 Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosisCancer Res 67 8065Google Scholar
Menssen, AHermeking, H 2002 Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genesProc Natl Acad Sci U S A 99 6274Google Scholar
Rosell, RSkrzypski, MJassem, ETaron, MBartolucci, RSanchez, J. JMendez, PChaib, IPerez-Roca, LSzymanowska, ARzyman, WPuma, FKobierska-Gulida, GFarabi, RJassem, J 2007 BRCA1: a novel prognostic factor in resected non-small-cell lung cancerPLoS ONE 2Google Scholar
Chen, H. YYu, S. LChen, C. HChang, G. CChen, C. YYuan, ACheng, C. LWang, C. HTerng, H. JKao, S. FChan, W. KLi, H. NLiu, C. CSingh, SChen, W. JChen, J. JYang, P. C 2007 A five-gene signature and clinical outcome in non-small-cell lung cancerN Engl J Med 356 11Google Scholar
Fossella, FPereira, J. Rvon Pawel, JPluzanska, AGorbounova, VKaukel, EMattson, K. VRamlau, RSzczesna, AFidias, PMillward, MBelani, C. P 2003 Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study groupJ Clin Oncol 21 3016Google Scholar
Scagliotti, G. VParikh, Pvon Pawel, JBiesma, BVansteenkiste, JManegold, CSerwatowski, PGatzemeier, UDigumarti, RZukin, MLee, J. SMellemgaard, APark, KPatil, SRolski, JGoksel, TMarinis, FSimms, LSugarman, K. PGandara, D 2008 Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancerJ Clin Oncol 26 3543Google Scholar
Cobo, MIsla, DMassuti, BMontes, ASanchez, J. MProvencio, MVinolas, NPaz-Ares, LLopez-Vivanco, GMunoz, M. AFelip, EAlberola, VCamps, CDomine, MSanchez, J. JSanchez-Ronco, MDanenberg, KTaron, MGandara, DRosell, R 2007 Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancerJ Clin Oncol 25 2747Google Scholar
Sobhian, BShao, GLilli, D. RCulhane, A. CMoreau, L. AXia, BLivingston, D. MGreenberg, R. A 2007 RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sitesScience 316 1198Google Scholar
Kim, HChen, JYu, X 2007 Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage responseScience 316 1202Google Scholar
Yan, JKim, Y. SYang, X. PLi, L. PLiao, GXia, FJetten, A. M 2007 The ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and functions in DNA damage repair responseCancer Res 67 6647Google Scholar
Yan, JYang, X. PKim, Y. SJetten, A. M 2008 RAP80 responds to DNA damage induced by both ionizing radiation and UV irradiation and is phosphorylated at Ser 205Cancer Res 68 4269Google Scholar
Kim, HHuang, JChen, J 2007 CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage responseNat Struct Mol Biol 14 710Google Scholar
Liu, ZWu, JYu, X 2007 CCDC98 targets BRCA1 to DNA damage sitesNat Struct Mol Biol 14 716Google Scholar
Yan, JKim, Y. SYang, X. PAlbers, MKoegl, MJetten, A. M 2007 Ubiquitin-interaction motifs of RAP80 are critical in its regulation of estrogen receptor alphaNucleic Acids Res 35 1673Google Scholar
Eelen, GVanden Bempt, IVerlinden, LDrijkoningen, MSmeets, ANeven, PChristiaens, M. RMarchal, KBouillon, RVerstuyf, A 2008 Expression of the BRCA1-interacting protein Brip1/BACH1/FANCJ is driven by E2F and correlates with human breast cancer malignancyOncogene 27 4233Google Scholar
Chen, XArciero, C. AWang, CBroccoli, DGodwin, A. K 2006 BRCC36 is essential for ionizing radiation-induced BRCA1 phosphorylation and nuclear foci formationCancer Res 66 5039Google Scholar
Yan, JJetten, A. M 2008 RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sitesCancer Lett 271Google Scholar
Wang, BElledge, S. J 2007 Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damageProc Natl Acad Sci U S A 104 20759Google Scholar
Huen, M. SGrant, RManke, IMinn, KYu, XYaffe, M. BChen, J 2007 RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assemblyCell 131 901Google Scholar
Mailand, NBekker-Jensen, SFaustrup, HMelander, FBartek, JLukas, CLukas, J 2007 RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteinsCell 131 887Google Scholar
Stewart, G. SWang, BBignell, C. RTaylor, A. MElledge, S. J 2003 MDC1 is a mediator of the mammalian DNA damage checkpointNature 421 961Google Scholar
Kim, HChen, J 2008 New players in the BRCA1-mediated DNA damage responsive pathwayMol Cells 25 457Google Scholar
Wu, WKoike, ATakeshita, TOhta, T 2008 The ubiquitin E3 ligase activity of BRCA1 and its biological functionsCell Div 3 1Google Scholar
Osorio, ABarroso, AGarcia, M. JMartinez-Delgado, BUrioste, MBenitez, J 2008 Evaluation of the BRCA1 interacting genes RAP80 and CCDC98 in familial breast cancer susceptibilityBreast Cancer Res Treat 113 371Google Scholar
Akbari, M. RGhadirian, PRobidoux, AFoumani, MSun, YRoyer, RZandvakili, ILynch, HNarod, S. A 2008 Germline RAP80 mutations and susceptibility to breast cancerBreast Cancer Res Treat 113 377Google Scholar
Marks, J. LGolas, BKirchoff, TMiller, V. ARiely, G. JOffit, KPao, W 2008 EGFR mutant lung adenocarcinomas in patients with germline BRCA mutationsJ Thorac Oncol 3 805Google Scholar
Lafarge, SSylvain, VFerrara, MBignon, Y. J 2001 Inhibition of BRCA1 leads to increased chemoresistance to microtubule-interfering agents, an effect that involves the JNK pathwayOncogene 20 6597Google Scholar
Husain, AHe, GVenkatraman, E. SSpriggs, D. R 1998 BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(IICancer Res 58 1120Google Scholar
Bhattacharyya, AEar, U. SKoller, B. HWeichselbaum, R. RBishop, D. K 2000 The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of and survival following treatment with the DNA cross-linking agent cisplatinJ Biol Chem 275 23899Google Scholar
Abbott, D. WThompson, M. ERobinson-Benion, CTomlinson, GJensen, R. AHolt, J. T 1999 BRCA1 expression restores radiation resistance in BRCA1-defective cancer cells through enhancement of transcription-coupled DNA repairJ Biol Chem 274 18808Google Scholar
Mullan, P. BQuinn, J. EGilmore, P. MMcWilliams, SAndrews, HGervin, CMcCabe, NMcKenna, SWhite, PSong, Y. HMaheswaran, SLiu, EHaber, D. AJohnston, P. GHarkin, D. P 2001 BRCA1 and GADD45 mediated G2/M cell cycle arrest in response to antimicrotubule agentsOncogene 20 6123Google Scholar
Quinn, J. EKennedy, R. DMullan, P. BGilmore, P. MCarty, MJohnston, P. GHarkin, D. P 2003 BRCA1 functions as a differential modulator of chemotherapy-induced apoptosisCancer Res 63 6221Google Scholar
Chabalier, CLamare, CRacca, CPrivat, MValette, ALarminat, F 2006 BRCA1 downregulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistanceCell Cycle 5 1001Google Scholar
Quinn, J. EJames, C. RStewart, G. EMulligan, J. MWhite, PChang, G. KMullan, P. BJohnston, P. GWilson, R. HHarkin, D. P 2007 BRCA1 mRNA expression levels predict for overall survival in ovarian cancer after chemotherapyClin Cancer Res 13 7413Google Scholar
Wang, LWei, JQian, XYin, HZhao, YYu, LWang, TLiu, B 2008 BMC Cancer 8 97
Taron, MRosell, RFelip, EMendez, PSouglakos, JRonco, M. SQueralt, CMajo, JSanchez, J. MSanchez, J. JMaestre, J 2004 BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancerHum Mol Genet 13 2443Google Scholar
Weberpals, JGarbuio, KO’Brien, AClark-Knowles, KDoucette, SAntoniouk, OGoss, GDimitroulakos, J 2009 The DNA repair proteins BRCA1 and as predictive markers in sporadic ovarian cancerInt J Cancer 124 806Google Scholar
Lynch, T. JBell, D. WSordella, RGurubhagavatula, SOkimoto, R. ABrannigan, B. WHarris, P. LHaserlat, S. MSupko, J. GHaluska, F. GLouis, D. NChristiani, D. CSettleman, JHaber, D. A 2004 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinibN Engl J Med 350 2129Google Scholar
Paez, J. GJanne, P. ALee, J. CTracy, SGreulich, HGabriel, SHerman, PKaye, F. JLindeman, NBoggon, T. JNaoki, KSasaki, HFujii, YEck, M. JSellers, W. RJohnson, B. EMeyerson, M 2004 EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapyScience 304 1497Google Scholar
Pao, WMiller, VZakowski, MDoherty, JPoliti, KSarkaria, ISingh, BHeelan, RRusch, VFulton, LMardis, EKupfer, DWilson, RKris, MVarmus, H 2004 EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinibProc Natl Acad Sci U S A 101 13306Google Scholar
Gazdar, A. FShigematsu, HHerz, JMinna, J. D 2004 Mutations and addiction to EGFR: the Achilles “heal” of lung cancers?Trends Mol Med 10 481Google Scholar
Johnson, B. EJanne, P. A 2005 Epidermal growth factor receptor mutations in patients with non-small cell lung cancerCancer Res 65 7525Google Scholar
Yun, C. HBoggon, T. JLi, YWoo, M. SGreulich, HMeyerson, MEck, M. J 2007 Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivityCancer Cell 11 217Google Scholar
Sequist, L. VMartins, R. GSpigel, DGrunberg, S. MSpira, AJanne, P. AJoshi, V. AMcCollum, DEvans, T. LMuzikansky, AKuhlmann, G. LHan, MGoldberg, J. SSettleman, JIafrate, A. JEngelman, J. AHaber, D. AJohnson, B. ELynch, T. J 2008 First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutationsJ Clin Oncol 26 2442Google Scholar
Carey, K. DGarton, A. JRomero, M. SKahler, JThomson, SRoss, SPark, FHaley, J. DGibson, NSliwkowski, M. X 2006 Kinetic analysis of epidermal growth factor receptor somatic mutant proteins shows increased sensitivity to the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinibCancer Res 66 8163Google Scholar
Jackman, D. MYeap, B. YSequist, L. VLindeman, NHolmes, A. JJoshi, V. ABell, D. WHuberman, M. SHalmos, BRabin, M. SHaber, D. ALynch, T. JMeyerson, MJohnson, B. EJanne, P. A 2006 Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinibClin Cancer Res 12 3908Google Scholar
Wei, JZou, ZQian, XDing, YXie, LSanchez, J. JZhao, YFeng, JLing, YLiu, YYu, LRosell, RLiu, B 2008 Br J Cancer 98 1398
Souglakos, JBoukovinas, ITaron, MMendez, PMavroudis, DTripaki, MHatzidaki, DKoutsopoulos, AStathopoulos, EGeorgoulias, VRosell, R 2008 Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabineBr J Cancer 98 1710Google Scholar
Ashworth, A 2008 A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repairJ Clin Oncol 26 3785Google Scholar
Farmer, HMcCabe, NLord, C. JTutt, A. NJohnson, D. ARichardson, T. BSantarosa, MDillon, K. JHickson, IKnights, CMartin, N. MJackson, S. PSmith, G. CAshworth, A 2005 Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategyNature 434 917Google Scholar
Edwards, S. LBrough, RLord, C. JNatrajan, RVatcheva, RLevine, D. ABoyd, JReis-Filho, J. SAshworth, A 2008 Nature 451 1111
Sakai, WSwisher, E. MKarlan, B. YAgarwal, M. KHiggins, JFriedman, CVillegas, EJacquemont, CFarrugia, D. JCouch, F. JUrban, NTaniguchi, T 2008 Secondary mutations as a mechanism of cisplatin resistance in -mutated cancersNature 451 1116Google Scholar
Adimoolam, SSirisawad, MChen, JThiemann, PFord, J. MBuggy, J. J 2007 HDAC inhibitor PCI-24781 decreases expression and inhibits homologous recombinationProc Natl Acad Sci U S A 104 19482Google Scholar
Arnold, N. BKetterer, KKleeff, JFriess, HBuchler, M. WKorc, M 2004 Thioredoxin is downstream of Smad7 in a pathway that promotes growth and suppresses cisplatin-induced apoptosis in pancreatic cancerCancer Res 64 3599Google Scholar
Ungerstedt, J. SSowa, YXu, W. SShao, YDokmanovic, MPerez, GNgo, LHolmgren, AJiang, XMarks, P. A 2005 Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitorsProc Natl Acad Sci U S A 102 673Google Scholar
Xu, WNgo, LPerez, GDokmanovic, MMarks, P. A 2006 Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitorProc Natl Acad Sci U S A 103 15540Google Scholar
Rouge, TGalluzzi, LOlaussen, K. AZermati, YTasdemir, ERobert, TRipoche, HLazar, VDessen, PHarper, FPierron, GPinna, GAraujo, NHarel-Belan, AArmand, J. PWong, T. WSoria, J. CKroemer, G 2007 A novel epidermal growth factor receptor inhibitor promotes apoptosis in non-small cell lung cancer cells resistant to erlotinibCancer Res 67 6253Google Scholar
Villeneuve, L. MReddy, M. ALanting, L. LWang, MMeng, LNatarajan, R 2008 Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetesProc Natl Acad Sci U S A 105 9047Google Scholar
Gonzalo, SJaco, IFraga, M. FChen, TLi, EEsteller, MBlasco, M. A 2006 DNA methyltransferases control telomere length and telomere recombination in mammalian cellsNat Cell Biol 8 416Google Scholar
Garcia-Cao, MO’Sullivan, RPeters, A. HJenuwein, TBlasco, M. A 2004 Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferasesNat Genet 36 94Google Scholar
Sonnberg, SSeet, B. TPawson, TFleming, S. BMercer, A. A 2008 Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexesProc Natl Acad Sci U S A 105 10955Google Scholar

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