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Targeting Merkel cell carcinoma by engineered T cells specific to T-antigens of Merkel cell polyomavirus.
CONCLUSIONS: Our findings demonstrate that MCC cells can be targeted by MCV Tag-specific TCRs. Although recent findings suggest that approximately half of MCC patients benefit from PD1 pathway blockade, additional patients may benefit if their endogenous T cell response can be augmented by infusion of transgenic MCV-specific T cells such as those described here. PMID: 29669806 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 18, 2018 Category: Cancer & Oncology Authors: Gavvovidis I, Leisegang M, Willimsky G, Miller NJ, Nghiem P, Blankenstein T Tags: Clin Cancer Res Source Type: research

A pan-cancer landscape of interactions between solid tumors and infiltrating immune cell populations.
CONCLUSIONS: We provide a comprehensive landscape of the characteristics of solid tumors that may influence (or be influenced by) the characteristics of their immune infiltrate. These results may help interpret the response of solid tumors to immunotherapies and guide the development of novel drug combination strategies. PMID: 29666300 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 17, 2018 Category: Cancer & Oncology Authors: Tamborero D, Rubio-Perez C, Muiños F, Sabarinathan R, Piulats JM, Muntasell A, Dienstmann R, Lopez-Bigas N, Gonzalez-Perez A Tags: Clin Cancer Res Source Type: research

Fratricide of NK Cells in Daratumumab Therapy for Multiple Myeloma Overcome by Ex Vivo Expanded Autologous NK Cells.
CONCLUSIONS: We unravel a fratricide mechanism for daratumumab-mediated NK cell depletion and provide a potential therapeutic strategy to overcome this side effect in daratumumab-treated MM patients. PMID: 29666301 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 17, 2018 Category: Cancer & Oncology Authors: Wang Y, Zhang Y, Hughes T, Zhang J, Caligiuri MA, Benson DM, Yu J Tags: Clin Cancer Res Source Type: research

Targeting Galectin-1 impairs castration-resistant prostate cancer progression and invasion.
CONCLUSIONS: Our study provides evidence that Gal-1 is an important target for mCRPC therapy, and LLS30 is a promising small molecule compound that can potentially overcome mCRPC. PMID: 29666302 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 17, 2018 Category: Cancer & Oncology Authors: Shih TC, Liu R, Wu CT, Li X, Xiao W, Deng X, Kiss Z, Wang T, Chen X, Carney RP, Kung HJ, Duan Y, Ghosh PM, Lam KS Tags: Clin Cancer Res Source Type: research

Gallium-67/68-labeled antibody fragments for immuno-SPECT/PET show low renal radioactivity without loss of tumor uptake.
This study was undertaken to evaluate the renal radioactivity levels of a newly designed 67Ga-labeled antibody fragment with a linkage cleaved by enzymes present on the brush border membrane (BBM) lining the lumen of the renal tubule. EXPERIMENTAL DESIGN: 67Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) was conjugated with an antibody Fab fragment through a Met-Val-Lys linkage (67Ga-NOTA-MVK-Fab) considering that a Met-Val sequence is a substrate of enzymes on the renal BBM and 67Ga-NOTA-Met is excreted from the kidney into the urine. The enzymatic recognition of the...
Source: Clinical Cancer Research - April 17, 2018 Category: Cancer & Oncology Authors: Uehara T, Yokoyama M, Suzuki H, Hanaoka H, Arano Y Tags: Clin Cancer Res Source Type: research

Strategic therapeutic targeting to overcome venetoclax resistance in aggressive B-cell lymphomas.
CONCLUSIONS: These findings demonstrate the on-target effect of venetoclax and offer potential mechanisms to overcome acquired and intrinsic venetoclax resistance through PI3K/AKT inhibition. PMID: 29666304 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 17, 2018 Category: Cancer & Oncology Authors: Pham LV, Huang S, Zhang H, Zhang J, Bell T, Zhou S, Pogue E, Ding Z, Lam L, Westin JR, Davis RE, Young KH, Medeiros LJ, Ford RJ, Nomie K, Zhang L, Wang M Tags: Clin Cancer Res Source Type: research

Integrated genomic and immunophenotypic classification of pancreatic cancer reveals three distinct subtypes with prognostic/predictive significance.
CONCLUSIONS: Immune host responses correlate with tumor characteristics leading to morphologically recognizable PDAC-subtypes with prognostic/predictive significance. PMID: 29661773 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2018 Category: Cancer & Oncology Authors: Wartenberg M, Cibin S, Zlobec I, Vassella E, Eppenberger-Castori SMM, Terracciano L, Eichmann M, Worni M, Gloor B, Perren A, Karamitopoulou E Tags: Clin Cancer Res Source Type: research

Accuracy, Safety, and Reliability of Novel Phase I Trial Designs.
Abstract A number of novel model-based and model-assisted designs have been proposed to find the maximum tolerated dose (MTD) in phase I clinical trials, but their differences and relative pros and cons are not clear to many practitioners. We review three model-based designs, including the continual reassessment method (CRM), dose escalation with overdose control (EWOC), and Bayesian logistic regression model (BLRM), and three model-assisted designs, including the modified toxicity probability interval (mTPI), Bayesian optimal interval (BOIN), and keyboard designs. We conduct numerical studies to assess their accu...
Source: Clinical Cancer Research - April 16, 2018 Category: Cancer & Oncology Authors: Zhou H, Yuan Y, Nie L Tags: Clin Cancer Res Source Type: research

Prospective clinical trial of ixazomib, dexamethasone and rituximab as primary therapy in Waldenstr öm macroglobulinemia.
CONCLUSION: IDR offers a highly effective and well tolerated, neuropathy-sparing regimen for primary therapy in patients with WM. This trial is registered at www.clinicaltrials.gov under ID NCT02400437. PMID: 29661775 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2018 Category: Cancer & Oncology Authors: Castillo JJ, Meid K, Gustine J, Dubeau T, Severns P, Hunter ZR, Yang G, Xu L, Treon SP Tags: Clin Cancer Res Source Type: research

Targeting the Leukemia Antigen PR1 with Immunotherapy for the treatment of Multiple Myeloma.
CONCLUSIONS: Collectively, our data demonstrate that PR1 is a novel tumor associated antigen target in MM and that MM is susceptible to immunotherapies that target cross-presented peptides. PMID: 29661776 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2018 Category: Cancer & Oncology Authors: Alatrash G, Perakis AA, Kerros C, Peters HL, Sukhumalchandra P, Zhang M, Jakher H, Zope M, Patenia RS, Sergeeva A, Yi S, Young KH, Philips AV, Herrmann AC, Garber HR, Qiao N, Weng J, St John LS, Lu S, Clise-Dwyer K, Mittendorf EA, Ma Q, Molldrem JJ Tags: Clin Cancer Res Source Type: research

Interferon-stimulated genes are involved in cross-resistance to radiotherapy in tamoxifen-resistant breast cancer.
CONCLUSIONS: Our data indicate that expression of ISGs by tumor cells is involved in acquired, treatment-induced resistance to tamoxifen and radiotherapy, and might play a role in intrinsic resistance via interaction with tumor infiltrating lymphocytes. PMID: 29661777 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2018 Category: Cancer & Oncology Authors: Post AEM, Smid M, Nagelkerke A, Martens JWM, Bussink J, Sweep FC, Span PN Tags: Clin Cancer Res Source Type: research

Immunogenomic analyses of advanced serous ovarian cancer reveal immune score is a strong prognostic factor and an indicator of chemo-sensitivity.
CONCLUSIONS: Our results reveal the drivers of the immune repertoire of advanced ovarian cancer and demonstrate the importance of immune score as an independent prognostic signature and a potent indicator of intratumoral immune status. PMID: 29661778 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2018 Category: Cancer & Oncology Authors: Di LJ, Hao D, Liu J, Chen M, Li J, Wang L, Wang G, Zhao Q Tags: Clin Cancer Res Source Type: research

Report from the SWOG Radiation Oncology Committee: Research Objectives Workshop 2017.
Conclusions. PMID: 29661779 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2018 Category: Cancer & Oncology Authors: Okunieff P, Casey-Sawicki K, Lockney NA, Hoppe BS, Enderling H, Pinnix CC, Welsh JW, Krishnan S, Yothers G, Brown JM, Knox SJ, Bristow RG, Spellman PT, Mitin T, Nabavizadeh N, Jaboin J, Manning HC, Feng FY, Galbraith SM, Solanki AA, Harkenrider MM, Tuli R Tags: Clin Cancer Res Source Type: research

Mitotic Exit dysfunction through the deregulation of APC/C characterizes cisplatin resistant state in epithelial ovarian cancer.
CONCLUSIONS: We provide the first evidence of APC/C dysfunction in cisplatin resistant state, suggesting that understanding APC/C functions in cisplatin resistant state could provide basis for developing novel mitotic exit based therapies to eradicate cisplatin resistant cancer cells. Our results also show that PLK1 down-regulation could underlie emergence of resistance to PLK1 targeted therapies in cancers. PMID: 29653924 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 13, 2018 Category: Cancer & Oncology Authors: Belur Nagaraj A, Kovalenko O, Avelar RA, Joseph P, Brown A, Surti A, Mantilla S, DiFeo A Tags: Clin Cancer Res Source Type: research

BRAF and MEK inhibitors increase PD1-positive melanoma cells leading to a potential lymphocyte-independent synergism with anti-PD1 antibody.
CONCLUSIONS: BRAF/MEKi increase the rates of PD1+ melanoma cells that may sustain tumor relapse, providing a lymphocyte-independent rational to explore combinatory strategies with anti-PD1 antibody. PMID: 29650750 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 12, 2018 Category: Cancer & Oncology Authors: Sanlorenzo M, Vujic I, Floris A, Novelli M, Gammaitoni L, Giraudo L, Macagno M, Leuci V, Rotolo R, Donini C, Basiricò M, Quaglino P, Fierro MT, Giordano S, Sibilia M, Carnevale-Schianca F, Aglietta M, Sangiolo D Tags: Clin Cancer Res Source Type: research

FDA Approval Summary: Niraparib for the maintenance treatment of patients with recurrent ovarian cancer in response to platinum-based chemotherapy.
dberg KB, Pierce WF, Ibrahim A, Kluetz PG, Blumenthal GM, Beaver JA, Pazdur R Abstract The Food and Drug Administration approved niraparib, a poly ADP ribose polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in each cohort was the primary endpoint. ...
Source: Clinical Cancer Research - April 12, 2018 Category: Cancer & Oncology Authors: Ison G, Howie LJ, Amiri-Kordestani L, Zhang L, Tang S, Sridhara R, Pierre V, Charlab R, Ramamoorthy A, Song P, Li F, Yu J, Manheng W, Palmby TR, Ghosh S, Horne HN, Lee EY, Philip R, Dave K, Chen XH, Kelly SL, Janoria KG, Banerjee A, Eradiri O, Dinin J, Go Tags: Clin Cancer Res Source Type: research

A survey on data reproducibility and the effect of publication process on the ethical reporting of laboratory research.
CONCLUSIONS: This survey indicates that trainees believe that the pressure to publish impacts honest reporting, mostly emanating from our system of rewards and advancement. The publication process itself impacts faculty and trainees and appears to influence a shift in their ethics from honest reporting ("negative data") to selective reporting, data falsification, or even fabrication. PMID: 29643062 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 11, 2018 Category: Cancer & Oncology Authors: Boulbes DR, Costello TJ, Baggerly KA, Fan F, Wang R, Bhattacharya R, Ye X, Ellis LM Tags: Clin Cancer Res Source Type: research

Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma.
CONCLUSIONS: Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m2 was confirmed as the recommended Phase II dose. PMID: 29643063 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 11, 2018 Category: Cancer & Oncology Authors: Hong DS, Moore KN, Patel MR, Grant SC, Burris HA, William WN, Jones S, Meric-Bernstam F, Infante J, Golden L, Zhang W, Martinez R, Wijayawardana SR, P Beckmann R, Bence Lin A, Eng C, Bendell JC Tags: Clin Cancer Res Source Type: research

Discovery of a glucocorticoid receptor (GR) activity signature using selective GR antagonism in ER-negative breast cancer.
CONCLUSIONS:  The GRsig discovered herein identifies high-risk ER-negative/GR-positive BCs most likely to relapse despite administration of adjuvant chemotherapy. Because GR antagonism can reverse expression of these genes, we propose that addition of a GR antagonist to chemotherapy may improve outcome of these high-risk patients. PMID: 29636357 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2018 Category: Cancer & Oncology Authors: West DC, Kocherginsky M, Tonsing-Carter EY, Dolcen DN, Hosfield DJ, Lastra RR, Sinnwell JP, Thompson KJ, Bowie KR, Harkless RV, Skor MN, Pierce CF, Styke SC, Kim CR, de Wet L, Greene GL, Boughey JC, Goetz MP, Kalari KR, Wang L, Fleming GF, Győrffy B, Con Tags: Clin Cancer Res Source Type: research

Resistance mechanisms to targeted therapies in ROS1+ and ALK+ non-small cell lung cancer.
Conclusions. PMID: 29636358 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2018 Category: Cancer & Oncology Authors: McCoach CE, Le A, Gowan K, Jones KL, Schubert L, Doak A, Estrada-Bernal A, Davies KD, Merrick DT, Bunn PA, Purcell WT, Dziadziuszko R, Varella-Garcia M, Aisner DL, Camidge DR, Doebele RC Tags: Clin Cancer Res Source Type: research

Targeting NAD+/PARP DNA repair pathway as a novel therapeutic approach to SDHB-mutated cluster I pheochromocytoma and paraganglioma.
CONCLUSIONS: In summary, our findings provide novel insights into an effective strategy for targeting cluster I PCPGs, especially those with SDHB mutations. PMID: 29636359 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2018 Category: Cancer & Oncology Authors: Pang Y, Lu Y, Caisova V, Liu Y, Bullova P, Huynh TT, Zhou Y, Yu D, Frysak Z, Hartmann I, Taieb D, Pacak K, Yang C, Yang C Tags: Clin Cancer Res Source Type: research

A First-in-Human Phase 1 Study of LY3023414, an Oral PI3K/mTOR Dual Inhibitor, in Patients with Advanced Cancer.
Conclusions: LY3023414 has a tolerable safety profile and single agent activity in patients with advanced cancers. The RP2D of LY3023414 monotherapy is 200 mg BID based on safety, tolerability, and PK/Pharmacodynamic data. PMID: 29636360 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2018 Category: Cancer & Oncology Authors: Bendell JC, Varghese AM, Hyman DM, Bauer TM, Pant S, Callies S, Lin J, Martinez R, Wickremsinhe ER, Fink A, Wacheck V, Moore KN Tags: Clin Cancer Res Source Type: research

Identification and validation of a 3-gene methylation classifier for HPV-based cervical screening on self-samples.
CONCLUSION: By genome-wide DNA methylation profiling on self-samples, we identified a highly effective 3-gene methylation classifier for direct triage on hrHPV-positive self-samples, which is superior to currently available methods. PMID: 29632006 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 9, 2018 Category: Cancer & Oncology Authors: Verlaat W, Snoek BC, Heideman DAM, Wilting SM, Snijders PJF, Novianti PW, van Splunter AP, Peeters CFW, van Trommel NE, Massuger LFAG, Bekkers RLM, Melchers WJ, van Kemenade FJ, Berkhof J, van de Wiel MA, Meijer CJLM, Steenbergen RDM Tags: Clin Cancer Res Source Type: research

Complete and durable responses in Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab and Dexamethasone.
CONCLUSIONS:   EBV+ PCNS-PTLD expressed lytic kinases and therapy with AZT, GCV, rituximab and dexamethasone provided durable responses. Induction of the lytic protein expression and increased cellular sensitivity to antiviral therapy after transfection with viral kinase cDNA provides a mechanistic rationale for our approach. PMID: 29632007 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 9, 2018 Category: Cancer & Oncology Authors: Dugan JP, Haverkos BM, Villagomez L, Martin L, Lustberg ME, Patton JT, Martin M, Huang Y, Nuovo G, Yan F, Cavaliere R, Fingeroth JD, Kenney SC, Ambinder RF, Lozanski G, Porcu P, Caligiuri MA, Baiocchi RA Tags: Clin Cancer Res Source Type: research

Change in topoisomerase 1 (Top1) positive circulating tumor cells impacts overall survival in patients with advanced breast cancer after treatment with etirinotecan pegol.
CONCLUSIONS: CTC Top1 expression following EP treatment may identify patients with MBC most likely to have an OS benefit. PMID: 29618616 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 4, 2018 Category: Cancer & Oncology Authors: Rugo HS, Cortes J, Awada A, O'Shaughnessey J, Twelves CJ, Im SA, Hannah A, Lu L, Sy S, Caygill K, Zajchowski DA, Davis DW, Tagliaferri MA, Hoch U, Perez EA Tags: Clin Cancer Res Source Type: research

Risk assessment after neoadjuvant chemotherapy in luminal breast cancer using a clinico-molecular predictor.
This study aimed to evaluate a modified EPclin test (mEPclin), a combination of EndoPredict (EP) score, post-neoadjuvant pathological tumor size and nodal status, for predicting the risk of distance recurrence after neoadjuvant chemotherapy (NACT) in patients with residual estrogen-receptor (ER)-positive/HER2-negative breast cancer (BC). We also compared the prognostic power of the mEPclin with that of the CPS-EG score. EXPERIMENTAL DESIGN: 428 formalin-fixed, paraffin-embedded tumor samples from GeparTrio and GeparQuattro studies were evaluated for mRNA expression of eight cancer-related and three reference genes. Th...
Source: Clinical Cancer Research - April 4, 2018 Category: Cancer & Oncology Authors: Loibl S, Weber K, Huober J, Krappmann K, Marmé F, Schem C, Engels K, Pfitzner BM, Kümmel S, Furlanetto J, Hartmann A, Darb-Esfahani S, Müller V, Staebler A, von Minckwitz G, Kronenwett R, Denkert C Tags: Clin Cancer Res Source Type: research

Inositol trisphosphate receptor type 3-mediated enhancement of EGFR and MET co-targeting efficacy in non-small cell lung cancer detected by 18F-fluorothymidine.
CONCLUSIONS: Our findings indicate that 18F-FLT PET/CT is able to detect the enhanced efficacy of EGFR and MET inhibitors in oncogene-driven NSCLC and that such enhancement is mediated by IP3R3 through its interaction with K-Ras. PMID: 29618618 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 4, 2018 Category: Cancer & Oncology Authors: Iommelli F, De Rosa V, Terlizzi C, Monti M, Panico M, Fonti R, Del Vecchio S Tags: Clin Cancer Res Source Type: research

Prevalent Homozygous Deletions of Type I Interferon and Defensin Genes in Human Cancers Associate with Immunotherapy Resistance.
CONCLUSIONS: Our analysis reveals that the homozygous deletion of interferon and defensin genes are prevalent in human cancers, and importantly this feature can be used as a novel prognostic biomarker for immunotherapy resistance. PMID: 29618619 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 4, 2018 Category: Cancer & Oncology Authors: Wang L, Ye Z, Dong H, Li Y, Ma T, Huang H, Leong HS, Eckel-Passow JE, Kocher JP, Liang H Tags: Clin Cancer Res Source Type: research

Orthoxenografts of testicular germ cell tumors demonstrate genomic changes associated with cisplatin resistance and identify PDMP as a re-sensitizing agent.
CONCLUSIONS: Orthoxenografts can be used preclinically to test the efficiency of drugs and also to identify prognosis markers and gene alterations acting as drivers of the acquired cisplatin resistance. PMID: 29618620 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 4, 2018 Category: Cancer & Oncology Authors: Piulats JM, Vidal A, García-Rodríguez FJ, Muñoz C, Nadal M, Moutinho C, Martínez-Iniesta M, Mora J, Figueras A, Guinó E, Padullés L, Aytés À, Mollevi DG, Puertas S, Martínez-Fernández C, Castillo W, Juliachs M, Moreno V, Muñoz P, Stefanovic M, Tags: Clin Cancer Res Source Type: research

ZIP4 Promotes Pancreatic Cancer Progression by Repressing ZO-1 and claudin-1 through a ZEB1-Dependent Transcriptional Mechanism.
CONCLUSIONS:  These findings suggest a novel pathway activated by ZIP4 controlling pancreatic cancer invasiveness and metastasis, which could serve as a new therapeutic target for this devastating disease. PMID: 29615456 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2018 Category: Cancer & Oncology Authors: Liu M, Yang J, Zhang Y, Zhou Z, Cui X, Zhang L, Fung KM, Zheng W, Allard FD, Yee EU, Ding K, Wu H, Liang Z, Zheng L, Fernandez-Zapico ME, Li Y, Bronze MS, Morris KT, Postier RG, Houchen CW, Yang J, Li M Tags: Clin Cancer Res Source Type: research

Mechanistic insights of an immunological adverse event induced by an anti-KIT antibody drug conjugate and mitigation strategies.
CONCLUSIONS: Our data suggests LOP628-mediated mast cell degranulation is the likely cause of HSR observed in the clinic due to co-engagement of the FcγR and KIT, resulting in mast cell activation. PMID: 29615457 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2018 Category: Cancer & Oncology Authors: L'Italien LE, Orozco O, Abrams TJ, Cantagallo L, Connor A, Desai J, Ebersbach H, Gelderblom H, Hoffmaster K, Lees E, Maacke H, Schleyer S, Skegro D, Lee-Hoeflich ST Tags: Clin Cancer Res Source Type: research

An Effective Epigenetic-PARP inhibitor Combination Therapy for Breast and Ovarian Cancers Independent of BRCA-mutations.
CONCLUSIONS:  The novel combination of the next generation DNMTi guadecitabine and the first-in-class PARPi talazoparib inhibited breast and ovarian cancers harboring either wildtype- or mutant-BRCA, supporting further clinical exploration of this drug combination in PARPi-resistant cancers. PMID: 29615458 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2018 Category: Cancer & Oncology Authors: Pulliam N, Fang F, Ozes AR, Tang J, Adewuyi A, Keer HN, Lyons JF, Baylin SB, Matei D, Nakshatri H, Rassool FV, Miller KD, Nephew KP Tags: Clin Cancer Res Source Type: research

Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers.
CONCLUSIONS: This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed. PMID: 29615459 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2018 Category: Cancer & Oncology Authors: Pozdeyev N, Gay L, Sokol ES, Hartmaier RJ, Deaver KE, Davis SN, French JD, Vanden Borre P, LaBarbera DV, Tan AC, Schweppe RE, Fishbein L, Ross JS, Haugen BR, Bowles DW Tags: Clin Cancer Res Source Type: research

Clinical and pathological characteristics of KEAP1- and NFE2L2- mutated non-small cell lung carcinoma (NSCLC).
CONCLUSION: KEAP1 and NFE2L2 mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and are found together with other cancer-related, partly targetable, aberrations. Both markers seem to be predictive for chemotherapy resistance. PMID: 29615460 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2018 Category: Cancer & Oncology Authors: Frank R, Scheffler M, Merkelbach-Bruse S, Ihle MA, Kron A, Rauer M, Ueckeroth F, Koenig K, Michels S, Fischer R, Eisert A, Fassunke J, Heydt C, Serke M, Ko YD, Gerigk U, Geist T, Kaminsky B, Heukamp L, Clement-Ziza M, Buettner R, Wolf J Tags: Clin Cancer Res Source Type: research

Molecular diagnosis of diffuse gliomas through sequencing of cell-free circulating tumour DNA from cerebrospinal fluid.
CONCLUSIONS: The genomic analysis of IDH1, IDH2, TP53, ATRX, TERT, H3F3A and HIST1H3B gene mutations in CSF ctDNA facilitates the diagnosis of diffuse gliomas in a timely manner to support the surgical and clinical management of these patients. PMID: 29615461 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2018 Category: Cancer & Oncology Authors: Martínez-Ricarte F, Mayor R, Martínez-Sáez E, Rubio-Pérez C, Pineda E, Cordero E, Cicuéndez M, Poca MA, Lopez-Bigas N, Ramón Y Cajal S, Vieito M, Carles J, Tabernero J, Vivancos A, Gallego S, Graus F, Sahuquillo J, Seoane J Tags: Clin Cancer Res Source Type: research

Cell-free DNA modification dynamics in abiraterone acetate-treated prostate cancer patients.
Oh G Abstract PURPOSE: Primary resistance to abiraterone acetate (AA), a key medication for the treatment of metastatic castration-resistant prostate cancer, occurs in 20-40% of patients. We aim to identify predictive biomarkers for AA-treatment response and understand the mechanisms related to treatment resistance. EXPERIMENTAL DESIGN: We used the Infinium Human Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA (cfDNA) in 108 plasma samples collected from 33 AA-treated patients. RESULTS: Thirty cytosines showed significant modification differences (FDR q
Source: Clinical Cancer Research - April 3, 2018 Category: Cancer & Oncology Authors: Gordevičius J, Kriščiūnas A, Groot DE, Yip SM, Susic M, Kwan A, Kustra R, Joshua AM, Chi KN, Petronis A, Oh G Tags: Clin Cancer Res Source Type: research

The Need for Neddylation: A Key to Achieving NED in Uveal Melanoma.
Abstract The ability of uveal melanoma cells to enter and exit dormancy plays a fundamental role in the development of metastatic disease.  Neddylation blockade is a promising strategy to prolong tumor dormancy via impaired angiogenesis and prevent the establishment of metastases via elimination of cancer stem-like cells. PMID: 29610291 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 2, 2018 Category: Cancer & Oncology Authors: Yang J, Hamid O, Carvajal RD Tags: Clin Cancer Res Source Type: research

Renin-angiotensin system inhibitors to mitigate cancer treatment-related adverse events.
Abstract Treatment-related side effects are a major clinical problem in cancer treatment. They lead to reduced compliance to therapy as well as increased morbidity and mortality. Well-known are the sequelae of chemotherapy on the heart, especially in childhood cancer survivors. Therefore, measures to mitigate the adverse events of cancer therapy may improve health and quality of life in cancer patients, both in short and long term. The renin angiotensin system (RAS) affects all hallmarks of cancer, and blockage of the RAS is associated with an improved outcome in several cancer types. There is also increasing evid...
Source: Clinical Cancer Research - April 2, 2018 Category: Cancer & Oncology Authors: Pinter M, Kwanten WJ, Jain RK Tags: Clin Cancer Res Source Type: research

Tumour-derived GM-CSF promotes granulocyte immunosuppression in mesothelioma patients.
CONCLUSIONS: Our study presents the mechanism behind the cross-talk between mesothelioma and the immune micro-environment and indicates that targeting GM-CSF could be a novel treatment strategy to augment immunotherapy. PMID: 29602801 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 30, 2018 Category: Cancer & Oncology Authors: Khanna S, Graef S, Mussai F, Thomas A, Wali N, Yenidunya BG, Yuan CM, Morrow B, Zhang J, Korangy F, Greten TF, Steinberg SM, Stetler-Stevenson M, Middleton G, De Santo C, Hassan R Tags: Clin Cancer Res Source Type: research

SMAD4 gene mutation renders pancreatic cancer resistance to radiotherapy through promotion of autophagy.
CONCLUSIONS: Our results demonstrate that defective SMAD4 is responsible for radioresistance in pancreatic cancer through induction of ROS and increased level of radiation-induced autophagy. PMID: 29602802 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 30, 2018 Category: Cancer & Oncology Authors: Wang F, Xia X, Yang C, Shen J, Mai J, Kim HC, Kirui D, Kang Y, Fleming JB, Koay EJ, Mitra S, Ferrari M, Shen H Tags: Clin Cancer Res Source Type: research

Functional precision medicine identifies novel druggable targets and therapeutic options in head and neck cancer.
CONCLUSIONS: High-throughput phenotyping with siRNA and drug libraries using patient derived tumor cells prioritizes mutated driver genes and identifies novel drug targets not revealed by genomic profiling. Functional profiling is a promising adjunct to DNA sequencing for precision oncology. PMID: 29599409 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 29, 2018 Category: Cancer & Oncology Authors: Xu C, Nikolova O, Basom R, Mitchell RM, Shaw R, Moser R, Park H, Gurley KE, Kao M, Green CL, Schaub FX, Diaz RL, Swan HA, Jang IS, Guinney J, Gadi VK, Margolin AA, Grandori C, Kemp CJ, Méndez E Tags: Clin Cancer Res Source Type: research

Clinical utility of cell-free DNA for the detection of ALK fusions and genomic mechanisms of ALK inhibitor resistance in non-small cell lung cancer.
CONCLUSIONS: In this cohort of cfDNA detected ALK fusions, we demonstrate that comprehensive cfDNA NGS provides a non-invasive means of detecting targetable alterations, and characterizing resistance mechanisms on progression. PMID: 29599410 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 29, 2018 Category: Cancer & Oncology Authors: McCoach CE, Blakely CM, Banks KC, Levy BM, Chue B, Raymond VM, Le A, Lee CE, Diaz J, Waqar SN, Purcell WT, Aisner DL, Davies KD, Lanman RB, Shaw AT, Doebele RC Tags: Clin Cancer Res Source Type: research

CD103+ tumor-resident CD8+ T cells are associated with improved survival in immunotherapy naive melanoma patients and expand significantly during anti-PD1 treatment.
Conclusions: Tumor-resident CD8+ T cell numbers are more prognostic than total CD8+ T cells in metastatic melanoma. In addition, they are likely to initiate response to anti-PD-1 and anti-LAG-3 treatments. We propose that the immune profile of these cells prior to treatment could inform strategies for immune checkpoint blockade. PMID: 29599411 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 29, 2018 Category: Cancer & Oncology Authors: Edwards J, Wilmott JS, Madore J, Gide TN, Quek C, Tasker A, Ferguson AL, Chen J, Hewavisenti R, Hersey P, Gebhardt T, Weninger W, Britton WJ, Saw R, Thompson JF, Menzies AM, Long GV, Scolyer RA, Palendira U Tags: Clin Cancer Res Source Type: research

Hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging of prostate cancer in vivo predicts efficacy of targeting the Warburg effect.
CONCLUSIONS: Hyperpolarized [1-13C]-pyruvate MRSI of prostate cancer predicts efficacy of targeting the Warburg effect. PMID: 29599412 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 29, 2018 Category: Cancer & Oncology Authors: Scroggins B, Matsuo M, White A, Saito K, Munasinghe JP, Sourbier C, Yamamoto K, Diaz V, Ichikawa K, Mitchell JB, Cherukuri MK, Citrin DE Tags: Clin Cancer Res Source Type: research

Combinatorial effects of VEGFR kinase inhibitor axitinib and oncolytic virotherapy in mouse and human glioblastoma stem-like cell models.
CONCLUSIONS: Systemic TKI (axitinib) beneficially combines with G47Δ-mIL12 to enhance anti-tumor efficacy in both immune-deficient and immune-competent orthotopic Saha et al 4 GBM models. Our results support further investigation of TKIs in combination with oHSV for GBM treatment. PMID: 29599413 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 29, 2018 Category: Cancer & Oncology Authors: Saha D, Wakimoto H, Peters CW, Antoszczyk SJ, Rabkin SD, Martuza RL Tags: Clin Cancer Res Source Type: research

T-Cell Dysfunction in Glioblastoma: Applying a New Framework.
Abstract A functional, replete T cell repertoire is an integral component to adequate immune surveillance and to the initiation and maintenance of productive anti-tumor immune responses. Glioblastoma (GBM), however, is particularly adept at sabotaging anti-tumor immunity, eliciting severe T cell dysfunction that is both qualitative and quantitative. Understanding and countering such dysfunction are among the keys to harnessing the otherwise stark potential of anti-cancer immune-based therapies. While T cell dysfunction in GBM is long described, newer immunologic frameworks now exist for re-classifying T cell defic...
Source: Clinical Cancer Research - March 28, 2018 Category: Cancer & Oncology Authors: Woroniecka KI, Rhodin KE, Chongsathidkiet P, Keith KA, Fecci PE Tags: Clin Cancer Res Source Type: research

5-Fluorouracil enhances Protoporphyrin IX accumulation and lesion clearance during photodynamic therapy of  actinic keratoses: A mechanism-based clinical trial.
CONCLUSIONS: Serial 5FU and PDT improves AK clearance by at least two mechanisms, enhanced photosensitizer accumulation and p53 induction. Because 5FU and PDT are FDA-approved modalities, the combined regimen can be readily employed in clinical practice to reduce AK burden and reduce SCC risk. ClinicalTrials.gov NCT01525329. PMID: 29593028 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 28, 2018 Category: Cancer & Oncology Authors: Maytin EV, Anand S, Riha M, Lohser S, Tellez A, Ishak R, Karpinski L, Sot J, Hu B, Denisyuk A, Davis SC, Kyei A, Vidimos A Tags: Clin Cancer Res Source Type: research

Exome sequencing of plasma DNA portrays the mutation landscape of colorectal cancer and discovers mutated VEGFR2 receptors as modulators of anti-angiogenic therapies.
CONCLUSIONS: Our study supports WES-cfDNA as a powerful platform for portraying the somatic mutation landscape of cancer and discovery of new resistance mechanisms to cancer therapies. Importantly, we discovered that VEGFR2 is somatically mutated across tumor types and that VEGFR2 mutants can be oncogenic and control sensitivity/resistance to antiangiogenic drugs. PMID: 29588308 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 27, 2018 Category: Cancer & Oncology Authors: Toledo RA, Garralda E, Mitsi M, Pons T, Monsech J, Vega E, Otero A, Albarran MI, Baños N, Duran Y, Bonilla V, Sarno F, Camacho Artacho M, Sánchez-Pérez T, Perea S, Alvarez R, De Martino Rodriguez A, Lietha D, Blanco-Aparicio C, Cubillo A, Dominguez O, Tags: Clin Cancer Res Source Type: research

Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer.
Abstract BACKGROUND: Tumor-infiltrating lymphocytes (TILs) in pre-treatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer-specific mortality (BCM) and overall mortality (OM) in TNBC. METHODS: Data on treatments and diagnostic tests from electronic medical records of two healthcare systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioecono...
Source: Clinical Cancer Research - March 26, 2018 Category: Cancer & Oncology Authors: Afghahi A, Purington N, Han SS, Desai M, Pierson E, Mathur MB, Seto T, Thompson CA, Rigdon J, Telli ML, Badve SS, Curtis C, West RB, Horst K, Gomez SL, Ford JM, Sledge GW, Kurian AW Tags: Clin Cancer Res Source Type: research

Biomarker discovery from we to me: Is learning from each patient a new approach?
Abstract The immune response is a dynamic multistep process, with a complex system regulation. Identification of predictive biomarkers is therefore challenging. Deep investigation of an exceptional responder to pembrolizumab in ovarian cancer identifies new mechanism of response and highlights the power of individualized medicine strategy. PMID: 29581132 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - March 26, 2018 Category: Cancer & Oncology Authors: Lheureux S Tags: Clin Cancer Res Source Type: research