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IDH1/2 mutations sensitize acute myeloid leukemia to PARP inhibition and this is reversed by IDH1/2-mutant inhibitors.
CONCLUSIONS: IDH1/2MUT AML cells are sensitive to PARP inhibitors as monotherapy but especially when combined with a DNA-damaging agent such as daunorubicin, whereas concomitant administration of IDH1/2MUT inhibitors during cytotoxic therapy decrease the efficacy of both agents in IDH1/2MUT AML. These results advocate in favor of clinical trials of PARP inhibitors either or not in combination with daunorubicin in IDH1/2MUT AML. PMID: 29339439 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 16, 2018 Category: Cancer & Oncology Authors: Molenaar RJ, Radivoyevitch T, Nagata Y, Khurshed M, Przychodzen B, Makishima H, Xu M, Bleeker FE, Wilmink JW, Carraway H, Mukherjee S, Sekeres MA, Van Noorden CJF, Maciejewski JP Tags: Clin Cancer Res Source Type: research

Repurposing tin mesoporphyrin as an immune checkpoint inhibitor shows therapeutic efficacy in preclinical models of cancer.
CONCLUSIONS: SnMP could represent a novel immune checkpoint therapy, which may improve the immunological response to chemotherapy. PMID: 29339440 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 16, 2018 Category: Cancer & Oncology Authors: Muliaditan T, Opzoomer JW, Caron J, Okesola M, Kosti P, Lall S, Van Hemelrijck M, Dazzi F, Tutt A, Grigoriadis A, Gillett C, Madden SF, Burchell JM, Kordasti S, Diebold SS, Spicer J, Arnold JN Tags: Clin Cancer Res Source Type: research

Correction: Prevention of Colitis and Colitis-Associated Colorectal Cancer by a Novel Polypharmacological Histone Deacetylase Inhibitor.
Authors: PMID: 29339353 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 15, 2018 Category: Cancer & Oncology Tags: Clin Cancer Res Source Type: research

Correction: Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.
Authors: PMID: 29339354 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 15, 2018 Category: Cancer & Oncology Tags: Clin Cancer Res Source Type: research

High-risk TP53 mutations are associated with extra nodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC).
CONCLUSIONS: ENE is one of the most significant markers of OSCC OS and DFS. There is a shift toward a more aggressive biological phenotype associated with high-risk mutations of the TP53 gene. Prospective clinical trials are required to determine whether TP53 mutational status can be used for personalized treatment decisions. PMID: 29330202 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 12, 2018 Category: Cancer & Oncology Authors: Sandulache VC, Michikawa C, Kataria P, Gleber-Netto FO, Bell D, Trivedi S, Rao X, Wang J, Zhao M, Jasser SA, Myers JN, Pickering CR Tags: Clin Cancer Res Source Type: research

Personalized RNA-medicine for pancreatic cancer.
CONCLUSIONS:  This general approach appears suitable for co-clinical validation of personalized RNA medicine and paves the way to prospectively identify patients with eligible miRNA profiles for personalized RNA-based therapy. PMID: 29330203 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 12, 2018 Category: Cancer & Oncology Authors: Gilles ME, Hao L, Huang L, Rupaimoole R, Lopez-Casas PP, Pulver E, Jeong JC, Muthuswamy SK, Hidalgo M, Bhatia SN, Slack FJ Tags: Clin Cancer Res Source Type: research

Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma.
Conclusions: In the adjuvant setting, higher pazopanib Ctrough was associated with improved DFS, and did not increase treatment discontinuations or grade 3/4 AEs with the exception of hypertension. PMID: 29330204 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 12, 2018 Category: Cancer & Oncology Authors: Sternberg C, Donskov F, Haas NB, Doehn C, Russo P, Elmeliegy MA, Baneyx G, Banerjee H, Aimone P, Motzer RJ Tags: Clin Cancer Res Source Type: research

Clinical utility of a STAT3-regulated microRNA-200 family signature with prognostic potential in early gastric cancer.
Conclusions: Collectively, our discovery of a STAT3-regulated, miR-200 family-associated gene signature specific for EGC, with predictive power, provides a molecular rationale to classify and stratify EGC patients for endoscopic treatment. PMID: 29330205 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 12, 2018 Category: Cancer & Oncology Authors: Yu L, Wu D, Gao H, Balic J, Tsykin A, Han TS, Liu YD, Kennedy CL, Li JK, Mao JQ, Tan P, Oshima M, Goodall GJ, Jenkins BJ Tags: Clin Cancer Res Source Type: research

Evolution of cytogenetically normal acute myeloid leukemia during therapy and relapse: An exome sequencing study of 50 patients.
CONCLUSION: Chemotherapy resistance might be acquired through gain of mutations. Insights into the evolution during therapy and disease progression lay the foundation for tailored approaches to treat or prevent relapse of CN-AML. PMID: 29330206 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 12, 2018 Category: Cancer & Oncology Authors: Greif PA, Hartmann L, Vosberg S, Stief S, Mattes R, Hellmann I, Metzeler KH, Herold T, Bamopoulos S, Kerbs P, Jurinovic V, Schumacher D, Pastore F, Bräundl K, Zellmeier E, Ksienzyk B, Konstandin N, Schneider S, Graf A, Krebs S, Blum H, Neumann M, Baldus Tags: Clin Cancer Res Source Type: research

Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA.
Abstract PURPOSE: Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging.  However, immunotherapy responses are uniquely challenging to interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation.  We hypothesized that monitoring tumor cell death in real-time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy.  Experimental Design: We compared longitudinal changes in ctDNA levels with changes in radiographic tumor...
Source: Clinical Cancer Research - January 12, 2018 Category: Cancer & Oncology Authors: Goldberg SB, Narayan A, Kole AJ, Decker RH, Teysir J, Carriero NJ, Lee A, Nemati R, Nath SK, Mane SM, Deng Y, Sukumar N, Zelterman D, Boffa DJ, Politi K, Gettinger S, Wilson LD, Herbst RS, Patel AA Tags: Clin Cancer Res Source Type: research

Evaluation of overall response rate and progression-free survival as potential surrogate endpoints for overall survival in immunotherapy trials.
CONCLUSIONS: While responders exhibited longer survival and PFS than non-responders, the trial-level and individual level associations were weak between PFS/ORR and OS. Modifications to PFS did not improve associations. PMID: 29326281 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 11, 2018 Category: Cancer & Oncology Authors: Mushti SL, Mulkey F, Sridhara R Tags: Clin Cancer Res Source Type: research

RNF126 as a biomarker of a poor prognosis in invasive breast cancer and CHK1 inhibitor efficacy in breast cancer cells.
CONCLUSIONS:  RNF126 protein is highly expressed in invasive BC tissue. The high expression of RNF126 is an independent predictor of a poor prognosis in invasive BC and is considered a potential biomarker of a cancer's responsiveness to CHK1 inhibitors. CHK1 inhibition targets BC cells expressing higher levels of RNF126 by enhancing replication stress. PMID: 29326282 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 11, 2018 Category: Cancer & Oncology Authors: Yang X, Pan Y, Qiu Z, Du Z, Zhang Y, Fa P, Gorityala S, Ma S, Li S, Chen C, Wang H, Xu Y, Yan C, Keri RA, Ma Z, Zhang J Tags: Clin Cancer Res Source Type: research

Expanded genomic profiling of circulating tumor cells in metastatic breast cancer patients to assess biomarker status and biology over time.
Conclusions: We demonstrate an approach for complete isolation of EPCAM-positive CTCs and downstream comprehensive transcriptional/genomic characterization to examine the biology and assess breast cancer biomarkers in these cells over time. PMID: 29311117 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 8, 2018 Category: Cancer & Oncology Authors: Magbanua MJM, Rugo HS, Wolfe DM, Hauranieh L, Roy R, Pendyala P, Sosa E, Scott JH, Lee JS, Pitcher BN, Hyslop TM, Barry WT, Isakoff SJ, Dickler MN, Van't Veer LJ, Park JW Tags: Clin Cancer Res Source Type: research

Therapeutic Challenge With a CDK 4/6 Inhibitor Induces an RB-dependent SMAC Mediated Apoptotic Response in Non-Small Cell Lung Cancer.
Conclusions: This study uncovers a novel function of RB activation to induce cellular apoptosis through therapeutic administration of a palbociclib and provides a rationale for the clinical evaluation of CDK 4/6 inhibitors in the treatment of NSCLC patients. PMID: 29311118 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 8, 2018 Category: Cancer & Oncology Authors: Thangavel C, Boopathi E, Liu Y, McNair C, Haber A, Perepelyuk M, Bhardwaj A, Addya S, Ertel A, Shoyele S, Birbe R, Salvino JM, Dicker AP, Knudsen KE, Den RB Tags: Clin Cancer Res Source Type: research

Genomic correlates of response to everolimus in aggressive radioiodine-refractory thyroid cancer: a phase II study.
Conclusions: Everolimus has significant anti-tumor activity in TC. While genomic profiling does not currently guide therapeutic selection in TC patients, these data have important implications when considering the use of an mTOR inhibitor in an era of precision medicine. PMID: 29301825 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Hanna GJ, Busaidy NL, Chau NG, Wirth LJ, Barletta JA, Calles A, Haddad RI, Kraft S, Cabanillas ME, Rabinowits G, O'Neill A, Limaye SA, Alexander EK, Moore FD, Misiukiewicz K, Thomas T, Nehs MA, Marqusee E, Lee SL, Janne PA, Lorch JH Tags: Clin Cancer Res Source Type: research

p53-reactive T cells are associated with clinical benefit in patients with platinum-resistant epithelial ovarian cancer after treatment with a p53 vaccine and gemcitabine chemotherapy.
CONCLUSIONS: p53MVA was well tolerated, but gemcitabine without steroid pre-treatment was intolerable in some patients. However, elevated p53-reactive CD4+ and CD8+T cell responses post therapy correlated with longer PFS. Therefore, if responses to p53MVA could be enhanced with alternative agents, superior clinical responses may be achievable. PMID: 29301826 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Hardwick NR, Frankel P, Ruel C, Kilpatrick J, Tsai W, Kos F, Kaltcheva TI, Leong L, Morgan R, Chung V, Tinsley R, Eng M, Wilczynski SP, Ellenhorn JDI, Diamond DJ, Cristea M Tags: Clin Cancer Res Source Type: research

Thy1-Targeted Microbubbles for Ultrasound Molecular Imaging of Pancreatic Ductal Adenocarcinoma.
Abstract PURPOSE: To engineer a dual human and murine Thy1-binding single-chain-antibody ligand (Thy1-scFv) for contrast microbubble-enhanced ultrasound molecular imaging of pancreatic ductal adenocarcinoma (PDAC). EXPERIMENTAL DESIGN:  Thy1-scFv were engineered using yeast-surface-display techniques. Binding to soluble human and murine Thy1 and to Thy1-expressing cells was assessed by flow cytometry. Thy1-scFv was then attached to gas-filled microbubbles to create MB Thy1-scFv. Thy1 binding of MB Thy1-scFv to Thy1-expressing cells was evaluated under flow shear stress conditions in flow-chamber experime...
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Abou-Elkacem L, Wang H, Chowdhury SM, Kimura RH, Bachawal SV, Gambhir SS, Tian L, Willmann JK Tags: Clin Cancer Res Source Type: research

Pancreatic juice mutation concentrations can help predict the grade of dysplasia in patients undergoing pancreatic surveillance.
Conclusions: Pancreatic juice mutation analysis using digital NGS has potential diagnostic utility in the evaluation of patients undergoing pancreatic surveillance. . PMID: 29301828 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Suenaga M, Yu J, Shindo K, Tamura K, Almario JAN, Zaykoski CM, Witmer PD, Fesharakizadeh S, Borges M, Lennon AM, Shin EJ, Canto MI, Goggins MG Tags: Clin Cancer Res Source Type: research

Identification of a novel, EBV-based antibody risk stratification signature for early detection of nasopharyngeal carcinoma in Taiwan.
Abstract BACKGROUND: Epstein-Barr virus (EBV) is necessary for the development of nasopharyngeal carcinoma (NPC). By adulthood, ~90% of individuals test EBV-positive, but only a fraction develop cancer. Factors that identify which individuals are most likely to develop disease, including differential antibody response to the virus, could facilitate detection at early stages when treatment is most effective. METHODS: We measured anti-EBV IgG and IgA antibody responses in 607 Taiwanese individuals. Antibodies were measured using a custom protein microarray targeting 199 sequences from 86 EBV proteins. Variation...
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Coghill AE, Pfeiffer RM, Proietti C, Hsu WL, Chien YC, Lekieffre L, Krause L, Teng A, Pablo J, Yu KJ, Lou PJ, Wang CP, Liu Z, Chen CJ, Middeldorp JM, Mulvenna JP, Bethony J, Hildesheim A, Doolan DL Tags: Clin Cancer Res Source Type: research

Activation of 4-1BB on liver myeloid cells triggers hepatitis via an interleukin-27 dependent pathway.
CONCLUSIONS: 4-1BB agonist antibodies trigger hepatitis via activation and expansion of interleukin-27-producing liver Kupffer cells and monocytes. Co-administration of CTLA-4 and/or CCR2 blockade may minimize hepatitis, but yield equal or greater antitumor immunity. PMID: 29301830 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Bartkowiak T, Jaiswal AR, Ager CR, Chin R, Chen CH, Budhani P, Ai M, Reilley MJ, Sebastian MM, Hong DS, Curran MA Tags: Clin Cancer Res Source Type: research

Efficacy, safety and pharmacokinetics of axitinib in nasopharyngeal carcinoma: a preclinical and phase 2 correlative study.
CONCLUSIONS: Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients. PMID: 29301831 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Hui EP, Ma BBY, Loong H, Mo F, Li L, King AD, Wang K, Ahuja AT, Chan CM, Hui CW, Wong CH, Chan AT Tags: Clin Cancer Res Source Type: research

Pharmacological inhibition of NOS activates ASK1/JNK pathway augmenting docetaxel-mediated apoptosis in triple negative breast cancer.
CONCLUSION: iNOS is a critical target for docetaxel resistance in TNBC. Pharmacological inhibition of NOS enhanced chemotherapy response in TNBC PDX models. Combination therapy may improve prognosis and prevent relapse in TNBC patients who have failed conventional chemotherapy. PMID: 29301832 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Dávila-González D, Choi DS, Rosato RR, Granados-Principal S, Kuhn JG, Li WF, Qian W, Chen W, Kozielski AJ, Wong HH, Dave B, Chang JC Tags: Clin Cancer Res Source Type: research

Establishing A Preclinical Multidisciplinary Board for Brain Tumors.
CONCLUSIONS:  We report a comprehensive preclinical trial platform to assess the therapeutic activity of conventional and novel treatments among rare brain tumor subtypes. It also enables the development of complex, combination treatment regimens that should deliver optimal trial designs for clinical testing.  Post-irradiation gemcitabine infusion should be tested as new treatments of SEP and CPC. PMID: 29301833 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2018 Category: Cancer & Oncology Authors: Nimmervoll B, Boulos N, Bianski BM, Dapper J, DeCuypere M, Shelat AA, Terranova S, Terhune HE, Gajjar A, Patel YT, Freeman BB, Onar-Thomas A, Stewart CF, Roussel MF, Guy RK, Merchant TE, Calabrese C, Wright KD, Gilbertson RJ Tags: Clin Cancer Res Source Type: research

Development and preclinical validation of a cysteine knottin peptide targeting Integrin αvβ6 for near-infrared fluorescent-guided surgery in pancreatic cancer.
Development and preclinical validation of a cysteine knottin peptide targeting Integrin αvβ6 for near-infrared fluorescent-guided surgery in pancreatic cancer. Clin Cancer Res. 2018 Jan 03;: Authors: Tummers WS, Kimura RH, Abou-Elkacem L, Vahrmeijer AL, Swijnenburg RJ, Willmann JK, Gambhir SS Abstract PURPOSE: Intraoperative near-infrared fluorescence (NIRF) imaging could help stratification for the proper primary treatment for patients with pancreatic ductal adenocarcinoma (PDAC), and achieve complete resection since it allows visualization of cancer in real time. Integrin αvβ6,...
Source: Clinical Cancer Research - January 3, 2018 Category: Cancer & Oncology Authors: Tummers WS, Kimura RH, Abou-Elkacem L, Vahrmeijer AL, Swijnenburg RJ, Willmann JK, Gambhir SS Tags: Clin Cancer Res Source Type: research

Development and validation of a gene signature for patients with head and neck squamous cell carcinomas treated by postoperative radio(chemo)therapy.
SE, Mönnich D, Zips D, Baretton GB, Buchholz F, Baumann M, Krause M, Löck S Abstract PURPOSE: The aim of this study was to identify and independently validate a novel gene signature predicting loco-regional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C). EXPERIMENTAL DESIGN: Gene expression analyses were performed using nanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patie...
Source: Clinical Cancer Research - January 3, 2018 Category: Cancer & Oncology Authors: Schmidt S, Linge A, Zwanenburg A, Leger S, Lohaus F, Krenn C, Appold S, Gudziol V, Nowak A, von Neubeck C, Tinhofer I, Budach V, Sak A, Stuschke M, Balermpas P, Rödel C, Bunea H, Grosu AL, Abdollahi A, Debus J, Ganswindt U, Belka C, Pigorsch SU, Combs SE Tags: Clin Cancer Res Source Type: research

Phase 1 trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF- β, in advanced solid tumors.
CONCLUSIONS: M7824 has a manageable safety profile in patients with heavily pretreated advanced solid tumors. Early signs of efficacy are encouraging and multiple expansion cohorts are ongoing in a range of tumors. PMID: 29298798 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 3, 2018 Category: Cancer & Oncology Authors: Strauss J, Heery C, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes LM, Christensen O, Mahnke L, Helwig C, Gulley JL Tags: Clin Cancer Res Source Type: research

Targeting HER2 Aberrations in Non-Small Cell Lung Cancer with Osimertinib.
CONCLUSIONS: Overall, our data indicated robust anti-tumor efficacy of osimertinib against multiple HER2 aberrations in lung cancer, either as a single agent or in combination with JQ1. Our study provides a strong rationale for future clinical trials using osimertinib either alone or in combination with epigenetic drugs to target aberrant HER2 in NSCLC patients. PMID: 29298799 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 3, 2018 Category: Cancer & Oncology Authors: Liu S, Li S, Hai J, Wang X, Chen T, Quinn MM, Gao P, Zhang Y, Ji H, Cross D, Wong KK Tags: Clin Cancer Res Source Type: research

FDG PET and FES PET Predict PFS on Endocrine Therapy-Letter.
PMID: 29298807 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 1, 2018 Category: Cancer & Oncology Authors: Mammatas LH, van Helden EJ, Verheul HMW, Menke-van der Houven van Oordt CW Tags: Clin Cancer Res Source Type: research

FDG PET and FES PET Predict PFS on Endocrine Therapy-Response.
PMID: 29298808 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 1, 2018 Category: Cancer & Oncology Authors: Kurland BF, Peterson LM, Linden HM, Mankoff DA Tags: Clin Cancer Res Source Type: research

RING-finger protein 6 amplification activates JAK/STAT3 pathway by modifying SHP-1 ubiquitylation and associates with poor outcome in colorectal cancer.
Conclusions Genomic amplification drives RNF6 overexpression in CRC. RNF6 may be a novel biomarker in colorectal carcinogenesis, and RNF6 may increase pSTAT3 level via promoting SHP-1 ubiquitylation and degradation. Targeting the RNF6/SHP-1/STAT3 axis provides a potential therapeutic option for RNF6-amplified tumors. PMID: 29288235 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 29, 2017 Category: Cancer & Oncology Authors: Liang Q, Ma D, Zhu X, Wang Z, Sun TT, Shen C, Yan T, Tian X, Yu T, Guo F, Tang J, Lin Y, Chen H, Zhou C, Ge Z, Zhong M, Chen J, Liu Q, Wang Z, Fang JY, Chen HY, Hong J Tags: Clin Cancer Res Source Type: research

CD47 Blockade as an Adjuvant Immunotherapy for Resectable Pancreatic Cancer.
CONCLUSIONS: These findings suggest that following surgical resection of PDAC, adjuvant immunotherapy with anti-CD47 antibody could lead to substantially improved outcomes for patients. PMID: 29288236 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 29, 2017 Category: Cancer & Oncology Authors: Michaels AD, Newhook TE, Adair SJ, Morioka S, Goudreau BJ, Nagdas S, Mullen MG, Persily JB, Bullock T, Slingluff CL, Ravichandran KS, Parsons JT, Bauer TW Tags: Clin Cancer Res Source Type: research

Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer - Early Results from the COMPASS Trial.
CONCLUSIONS: Prospective genomic profiling of advanced PDAC is feasible and our early data indicate that chemotherapy response differs among patients with different genomic/transcriptomic subtypes. PMID: 29288237 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 29, 2017 Category: Cancer & Oncology Authors: Aung KL, Fischer SE, Denroche RE, Jang GH, Dodd A, Creighton S, Southwood B, Liang SB, Chadwick D, Zhang A, O'Kane GM, Albaba HAA, Moura S, Grant RC, Miller JK, Mbabaali F, Pasternack D, Lungu IM, Bartlett JMS, Ghai S, Lemire M, Holter S, Connor AA, Moffi Tags: Clin Cancer Res Source Type: research

Immunotherapy of MDS: you can run, but you can't hide.
Abstract The hypomethylating agent decitabine induces expression of the cancer testis antigen NY-ESO-1 in the myeloid cells of patients with myelodysplastic syndrome (MDS).  MDS patients treated with decitabine and an NY-ESO-1 vaccine developed NY-ESO-1-specific T cell responses directed against their abnormal myeloid cells, raising hopes for combinatorial immunotherapy of this disease. PMID: 29284705 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 28, 2017 Category: Cancer & Oncology Authors: Fuchs EJ Tags: Clin Cancer Res Source Type: research

PIK3CA C2 domain deletions hyperactivate phosphoinositide 3-kinase (PI3K), generate oncogene dependence and are exquisitely sensitive to PI3K α inhibitors.
CONCLUSIONS: C2 domain deletions in PIK3CA generate PI3K dependence and should be considered biomarkers of sensitivity to PI3K inhibitors. PMID: 29284706 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 28, 2017 Category: Cancer & Oncology Authors: Croessmann S, Sheehan JH, Lee KM, Sliwoski GR, He J, Nagy RJ, Riddle DA, Mayer IA, Balko JM, Lanman RB, Miller V, Cantley LC, Meiler J, Arteaga CL Tags: Clin Cancer Res Source Type: research

Structural alterations of MET trigger response to MET kinase inhibition in lung adenocarcinoma patients.
CONCLUSIONS: Crizotinib leads to a clinical response in patients with MET rearrangements. Our functional analyses together with the clinical data suggest that these structural alterations may represent actionable targets in lung cancer patients. PMID: 29284707 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 28, 2017 Category: Cancer & Oncology Authors: Plenker D, Bertrand M, de Langen AJ, Riedel R, Lorenz C, Scheel AH, Müller JN, Brägelmann J, Daßler-Plenker J, Kobe C, Persigehl T, Kluge A, Wurdinger T, Schellen P, Hartmann G, Zacherle T, Menon R, Thunnissen E, Büttner R, Griesinger F, Wolf J, Heuka Tags: Clin Cancer Res Source Type: research

ESR1 methylation: a liquid biopsy-based epigenetic assay for the follow up of patients with metastatic breast cancer receiving endocrine treatment.
CONCLUSIONS: We report for the first time the detection of ESR1 methylation in CTCs and a high concordance with paired plasma-ctDNA. ESR1 methylation in CTCs was associated with lack of response to everolimus/exemestane regimen. ESR1 methylation should be further evaluated as a potential liquid biopsy-based biomarker. PMID: 29284708 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 28, 2017 Category: Cancer & Oncology Authors: Mastoraki S, Strati A, Tzanikou E, Chimonidou M, Politaki H, Voutsina A, Psyrri A, Georgoulias V, Lianidou ES Tags: Clin Cancer Res Source Type: research

Exploration of a Novel Intermediate Response Endpoint in Immunotherapy Clinical Studies.
CONCLUSION: The IME was moderately associated with OS, and the association appeared to be stronger than the association observed between RECIST-defined ORR and OS.  However, the analyses conducted in this research are exploratory and further evaluation is needed before using this endpoint in future studies. PMID: 29279318 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 26, 2017 Category: Cancer & Oncology Authors: Gao X, Zhang L, Sridhara R Tags: Clin Cancer Res Source Type: research

Survival of cancer stem-like cells under metabolic stress via CaMK2 α-mediated upregulation of sarco/endoplasmic reticulum calcium ATPase expression.
CONCLUSIONS: The current study provides compelling evidence that CaMK2α acts as a key anti-apoptosis regulator in metabolic stress-resistant CSCs by activating NFκB. The latter induces expression of SERCA, allowing survival in glucose-deprived conditions. Importantly, our combination therapeutic strategy provides a novel approach for the clinical application of CSC treatment. PMID: 29279319 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 26, 2017 Category: Cancer & Oncology Authors: Park KC, Kim SW, Jeon JY, Jo AR, Choi HJ, Kim JM, Lee HG, Kim Y, Mills GB, Noh SH, Lee MG, Park ES, Cheong JH Tags: Clin Cancer Res Source Type: research

Biomarker Based Therapy in Pancreatic Ductal Adenocarcinoma: An Emerging Reality?
Abstract Over the last decade many of the major solid organ cancers have seen improvements in survival due to development of novel therapeutics and corresponding biomarkers that predict treatment efficacy or resistance. In contrast, in pancreatic ductal adenocarcinoma (PDAC) favorable outcomes remain challenging, in part related to the lack of validated biomarkers for patient and treatment selection and thus optimal clinical decision-making. Nonetheless, increasingly therapeutic development for PDAC is accompanied by bioassays to evaluate response and study mechanism of actions with a corresponding increase in the...
Source: Clinical Cancer Research - December 21, 2017 Category: Cancer & Oncology Authors: Krantz BA, O'Reilly EM Tags: Clin Cancer Res Source Type: research

Alteration of the tumor stroma using a consensus DNA vaccine targeting Fibroblast Activation Protein (FAP) synergizes with anti-tumor vaccine therapy in mice.
CONCLUSIONS: These results suggest that immune therapy targeting tumor antigens in combination with a micro-consensus FAP vaccine provides a two fisted punch inducing responses that target both the tumor microenvironment and tumor cells directly. PMID: 29269377 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 21, 2017 Category: Cancer & Oncology Authors: Duperret EK, Trautz A, Ammons D, Perales-Puchalt A, Wise MC, Yan J, Reed C, Weiner DB Tags: Clin Cancer Res Source Type: research

Tumor side as model of  integrative molecular classification of colorectal cancer.
Tumor side as model of integrative molecular classification of colorectal cancer. Clin Cancer Res. 2017 Dec 21;: Authors: Dienstmann R Abstract It has long since been recognized that colorectal cancer is molecularly heterogeneous and its clinical behavior differs if primary tumor was located in the right or left side of the colon. Recent studies have shown that part of this heterogeneity is captured by the anatomical location of the tumor. PMID: 29269378 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 21, 2017 Category: Cancer & Oncology Authors: Dienstmann R Tags: Clin Cancer Res Source Type: research

Loss-of-function mutations in Calcitonin receptor (CALCR) identify highly aggressive glioblastoma with poor outcome.
Conclusions We demonstrate CT-CALCR signaling axis is an important tumor suppressor pathway in glioma and establish CALCR as a novel therapeutic target for GBM. PMID: 29263181 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 20, 2017 Category: Cancer & Oncology Authors: Pal J, Patil V, Kumar A, Kaur K, Sarkar C, Somasundaram K Tags: Clin Cancer Res Source Type: research

Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer.
CONCLUSIONS: Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease. PMID: 29263182 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 20, 2017 Category: Cancer & Oncology Authors: Tucker DW, Getchell CR, McCarthy ET, Ohman AW, Sasamoto N, Xu S, Ko JY, Gupta M, Shafrir AL, Medina JE, Lee JJ, Macdonald LA, Malik A, Hasselblatt KT, Li W, Zhang H, Kaplan SJ, Murphy G, Hirsch MS, Liu J, Matulonis UA, Terry KL, Lian CG, Dinulescu DM Tags: Clin Cancer Res Source Type: research

Optical analysis of glioma: Fourier-transform infrared spectroscopy reveals the IDH1 mutation status.
Conclusions: Here, we show that vibrational spectroscopy reveals the IDH1 genotype of glioma. Because it can provide information in seconds, an implementation into the intraoperative workflow might allow simple and rapid online diagnosis of IDH1 genotype. The intraoperative confirmation of IDH1 mutation status might guide the decision to pursue definitive neurosurgical resection and guide future in situ therapies of infiltrative gliomas. PMID: 29259030 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 19, 2017 Category: Cancer & Oncology Authors: Uckermann O, Juratli TA, Galli R, Conde M, Wiedemuth R, Krex D, Geiger KD, Temme A, Schackert G, Koch E, Steiner G, Kirsch M Tags: Clin Cancer Res Source Type: research

Novel Targeting of Transcription and Metabolism in Glioblastoma.
CONCLUSIONS: TG02 inhibits multiple survival mechanisms and synergistically decreases energy production with temozolomide, representing a promising therapeutic strategy in GBM, currently under investigation in an ongoing clinical trial. PMID: 29254993 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 18, 2017 Category: Cancer & Oncology Authors: Su YT, Chen R, Wang H, Song H, Zhang Q, Chen LY, Lappin H, Vasconcelos G, Lita A, Maric D, Li A, Celiku O, Zhang W, Meetze KA, Estok T, Larion M, Abu-Asab M, Zhuang Z, Yang C, Gilbert MR, Wu J Tags: Clin Cancer Res Source Type: research

Homologous Recombination Deficiency and Platinum-Based Therapy Outcomes in Advanced Breast Cancer.
Conclusions: Our findings not only independently validate HRDetect, but also provide the first evidence of its association with platinum response in advanced breast cancer. We demonstrate that HRD mutation signatures may offer clinically relevant information independently of BRCA1/2 mutation status and hope this work will guide the development of clinical trials. Clin Cancer Res; 23(24); 7521-30. ©2017 AACR. PMID: 29246904 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2017 Category: Cancer & Oncology Authors: Zhao EY, Shen Y, Pleasance E, Kasaian K, Leelakumari S, Jones M, Bose P, Ch'ng C, Reisle C, Eirew P, Corbett R, Mungall KL, Thiessen N, Ma Y, Schein JE, Mungall AJ, Zhao Y, Moore RA, Den Brok W, Wilson S, Villa D, Shenkier T, Lohrisch C, Chia S, Yip S, Ge Tags: Clin Cancer Res Source Type: research

Genome-wide association study identifies a new locus at 7q21.13 associated with hepatitis B virus-related hepatocellular carcinoma.
CONCLUSIONS: Our findings highlight a novel locus at 7q21.13 conferring both susceptibility and prognosis to HBV-related HCC, and suggest the CDK14 gene to be the functional target of the 7q21.13 locus. PMID: 29246937 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2017 Category: Cancer & Oncology Authors: Zhou GQ, Zhang H, He F, Li Y, Zhai Y, Song Q, Zhang H, Cao P, Ping J, Liu X, Guo B, Liu G, Song J, Zhang Y, Yang A, Yan H, Yang L, Cui Y, Ma Y, Xing J, Shen X, Zhang H, An J, Bei JX, Jia W, Kang L, Liu L, Yuan D, Hu Z, Shen H, Lu L, Wang X, Li H, Liu TT Tags: Clin Cancer Res Source Type: research

Ipilimumab plus Lenalidomide after Allogeneic and Autologous Stem Cell Transplantation for Patients with Lymphoid Malignancies.
CONCLUSIONS: Our early-phase data suggested that ipilimumab plus lenalidomide is well tolerated after HSCT. Adverse events did not differ significantly between the allogeneic and autologous groups. PMID: 29246938 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2017 Category: Cancer & Oncology Authors: Khouri IF, Fernandez Curbelo I, Turturro F, Jabbour E, Milton DR, Bassett RL, Vence L, Allison JP, Gulbis AM, Sharma P Tags: Clin Cancer Res Source Type: research

Merkel cell carcinoma patients presenting without a primary lesion have elevated markers of immunity, higher tumor mutation burden and improved survival.
Abstract PURPOSE: Patients presenting with nodal Merkel cell carcinoma without an identifiable (unknown) primary lesion (MCC-UP) are nearly twice as likely to survive compared to similarly staged patients with known primary lesions (MCC-KP). The basis of this previously reported finding is unclear. EXPERIMENTAL DESIGN: Survival analyses and markers of immunity were evaluated in 123 patients with advanced MCC. Whole exome sequence data was analyzed from 16 tumors. RESULTS: As in prior studies, patients with nodal MCC-UP had strikingly improved MCC-specific survival as compared to MCC-KP patients (HR 0.297, p
Source: Clinical Cancer Research - December 15, 2017 Category: Cancer & Oncology Authors: Vandeven NA, Lewis CW, Makarov V, Riaz N, Paulson KG, Hippe DS, Bestick A, Doumani R, Marx T, Takagishi SR, Chan TA, Choi J, Nghiem P Tags: Clin Cancer Res Source Type: research

HSP27-mediated Extracellular and Intracellular Signaling Pathways Synergistically Confer Chemo-Resistance in Squamous Cell Carcinoma of Tongue.
CONCLUSIONS: HSP27 plays pivotal role in chemo-resistance of SCCT cells via a synergistic extracellular and intracellular signaling. HSP27 may represent a potential biomarker and therapeutic target for precision SCCT treatment. PMID: 29246940 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2017 Category: Cancer & Oncology Authors: Zheng G, Zhang Z, Liu H, Xiong Y, Luo L, Jia X, Peng C, Zhang Q, Li N, Gu Y, Lu M, Song Y, Pan H, Liu J, Liu W, He Z Tags: Clin Cancer Res Source Type: research