A Clinical Applicable Gene Expression Classifier Reveals Intrinsic and Extrinsic Contributions to Consensus Molecular Subtypes in Primary and Metastatic Colon Cancer.
CONCLUSION: We describe the utility of a Nanostring panel for CMS classification of FFPE clinical samples. Our work reveals the impact of intrinsic and extrinsic factors on CRC heterogeneity during disease progression. PMID: 31004000 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 19, 2019 Category: Cancer & Oncology Authors: Piskol R, Huw LY, Sergin I, Kim D, Kljavin NM, Tam R, Patel R, Burton J, Penuel E, Qu X, Koeppen H, Sumiyoshi T, de Sauvage FJ, Lackner MR, de Sousa E Melo F, Kabbarah O, Klijn C, Modrusan Z Tags: Clin Cancer Res Source Type: research

Tumor lysis, adverse events, and dose adjustments in 297 venetoclax treated CLL in routine clinical practice.
CONCLUSION: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety. PMID: 31004001 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 19, 2019 Category: Cancer & Oncology Authors: Roeker LE, Fox CP, Eyre TA, Brander D, Allan JN, Schuster SJ, Nabhan C, Hill BT, Shah NN, Lansigan F, Sarraf Yazdy M, Cheson BD, Lamanna N, Singavi AK, Coombs CC, Barr PM, Skarbnik AP, Shadman M, Ujjani CS, Tuncer HH, Winter AM, Rhodes J, Dorsey C, Morse Tags: Clin Cancer Res Source Type: research

Co-targeting of BCL2 with venetoclax and MCL1 with S63845 is synthetically lethal in vivo in relapsed mantle cell lymphoma.
CONCLUSIONS: Our data strongly support investigation of VTX in combination with S63845 as an innovative treatment strategy for chemoresistant MCL patients with adverse cytogenetics in the clinical grounds. PMID: 31004002 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 19, 2019 Category: Cancer & Oncology Authors: Prukova D, Andera L, Nahacka Z, Karolova J, Svaton M, Klanova M, Havranek O, Soukup J, Svobodova K, Zemanova Z, Tuskova D, Pokorna E, Helman K, Forsterova K, Pacheco-Blanco M, Vockova P, Berkova A, Fronkova E, Trneny M, Klener P Tags: Clin Cancer Res Source Type: research

A constitutional activating MET mutation makes the genetic link between malignancies and chronic inflammatory diseases.
CONCLUSIONS: Our study opens a considerable field of application in the domain of constitutional genetics, to establish genetic links between cancers and other very different severe diseases. PMID: 31004003 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 19, 2019 Category: Cancer & Oncology Authors: Morad EB, Do Cruzeiro M, Leboeuf C, Loisel-Ferreira I, Fédronie C, Ferreira C, Ait El Far R, Ziol M, Espié M, Falgarone G, Cassinat B, Kiladjian JJ, Feugeas JP, Janin A, Bousquet G Tags: Clin Cancer Res Source Type: research

Down-regulation of human DAB2IP Gene Expression in Renal Cell Carcinoma Results in Resistance to Ionizing Radiation.
CONCLUSIONS: In this study, we unveil that loss of DAB2IP resulted in elevated PARP-1 protein is associated with IR-resistance in RCC. These results provide a new targeting strategy to improve the efficacy of radiotherapy of RCC. PMID: 31000589 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 18, 2019 Category: Cancer & Oncology Authors: Yun EJ, Lin CJ, Dang A, Hernandez E, Guo J, Chen WM, Allison J, Kim N, Kapur P, Brugarolas J, Wu K, He D, Lai CH, Lin H, Saha D, Baek ST, Chen BPC, Hsieh JT Tags: Clin Cancer Res Source Type: research

A novel mechanism driving poor-prognosis prostate cancer: overexpression of the DNA repair gene, ribonucleotide reductase small subunit M2 (RRM2).
CONCLUSIONS: We propose that increased expression of RRM2 is a mechanism driving poor patient outcomes in PC and that its inhibition may be of significant therapeutic value. PMID: 30996073 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 17, 2019 Category: Cancer & Oncology Authors: Mazzu YZ, Armenia J, Chakraborty G, Yoshikawa Y, Coggins S, Nandakumar S, Gerke T, Pomerantz M, Qiu X, Zhao H, Atiq MO, Khan NA, Komura K, Lee GM, Fine SW, Bell C, O'Connor E, Long H, Freedman M, Kim B, Kantoff PW Tags: Clin Cancer Res Source Type: research

Developments in the space of new MAPK pathway inhibitors for BRAF-mutant melanoma.
Abstract The characterization of the MAPK signaling pathway has led to the development of multiple promising targeted therapy options for a subset of patients with metastatic melanoma. The combination of BRAF and MEK inhibitors represents an FDA-approved standard of care in patients with metastatic and resected BRAF mutated melanoma. There are currently three FDA-approved BRAF/MEK inhibitor combinations for the treatment of patients with BRAF mutated melanoma. While there have been significant advances in the field of targeted therapy, further exploration of new targets within the MAPK pathway will strengthen ther...
Source: Clinical Cancer Research - April 16, 2019 Category: Cancer & Oncology Authors: Cohen JV, Sullivan RJ Tags: Clin Cancer Res Source Type: research

Comparative analysis of AR variant AR-V567es mRNA detection systems reveals eminent variability and questions the role as a clinical biomarker in prostate cancer.
CONCLUSIONS: Validation of biomarker detection approaches is one of the most critical steps prior to transfer into clinical application. By performing comparative analysis of different detection approaches we revealed eminent variability among previously described systems. Furthermore, we demonstrate an overestimation of AR-V567es in PC, presumably due to non-specific detection of AR-FL mRNA. Therefore, any correlation between AR-V567es expression and clinical responses is highly doubtful and does not reflect the biological nature of the disease. PMID: 30992298 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2019 Category: Cancer & Oncology Authors: Bernemann C, Humberg V, Thielen B, Steinestel J, Chen X, Duensing S, Schrader AJ, Boegemann M Tags: Clin Cancer Res Source Type: research

Multidrug cancer therapy in metastatic castrate-resistant prostate cancer: An evolution-based strategy.
CONCLUSION: Mathematical models can integrate evolutionary dynamics into multidrug cancer clinical trials. This has the potential to improve outcomes and to develop clinical trials in which these mathematical models are also used to estimate the mechanism(s) of treatment failure and explore alternative strategies to improve outcomes in future trials. PMID: 30992299 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2019 Category: Cancer & Oncology Authors: West JB, Dinh MN, Brown JS, Zhang J, Anderson AR, Gatenby RA Tags: Clin Cancer Res Source Type: research

Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence.
CONCLUSIONS: This study demonstrates that patient-specific ctDNA analysis can be a sensitive and specific approach for disease surveillance for breast cancer patients. More importantly, earlier detection of up to two years provides a possible window for therapeutic intervention. PMID: 30992300 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2019 Category: Cancer & Oncology Authors: Coombes C, Page K, Salari R, Hastings RK, Armstrong AC, Ahmed S, Ali S, Cleator SJ, Kenny LM, Stebbing J, Rutherford MJ, Sethi H, Boydell AR, Swenerton R, Fernandez-Garcia D, Gleason K, Goddard KS, Guttery DS, Assaf Z, Wu HT, Natarajan P, Moore DA, Primro Tags: Clin Cancer Res Source Type: research

A Phase 1/2 Trial of MEC (Mitoxantrone, Etoposide, Cytarabine) in Combination with Ixazomib for Relapsed/ Refractory Acute Myeloid Leukemia.
CONCLUSIONS: These results are encouraging but a randomized trial is needed to address whether the addition of ixazomib to MEC improves outcome. Gene expression profiling also helped us identify predictors of response and potentially novel therapeutic targets. PMID: 30992301 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2019 Category: Cancer & Oncology Authors: Advani A, Cooper BW, Visconte V, Elson P, Chan R, Carew JS, Wei W, Mukherjee S, Gerds A, Carraway H, Nazha A, Hamilton B, Sobecks RM, Caimi PF, Tomlinson B, Malek E, Little J, Miron A, Pink JJ, Maciejewski JP, Kalaycio ME, De Lima M, Unger A, Sekeres MA Tags: Clin Cancer Res Source Type: research

Machine Learning to Build and Validate a Model for Radiation Pneumonitis Prediction in Patients with Non-Small-Cell Lung Cancer.
Conclusion By machine learning, this study has developed and validated a comprehensive model integrating inflammatory cytokines with clinical variables to predict RP2 before RT which provides an opportunity to guide clinicians. PMID: 30992302 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2019 Category: Cancer & Oncology Authors: Yu H, Wu H, Wang W, Jolly S, Jin JY, Hu C, Kong FS Tags: Clin Cancer Res Source Type: research

Clinical Utility of Comprehensive Cell-Free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non-Small Cell Lung Cancer.
Abstract PURPOSE: Complete and timely tissue genotyping is challenging, leading to significant numbers of patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) being undergenotyped for all eight genomic biomarkers recommended by professional guidelines. We aimed to demonstrate non-inferiority of comprehensive cell-free DNA (cfDNA) relative to physician discretion standard-of-care (SOC) tissue genotyping to identify guideline-recommended biomarkers in patients with mNSCLC. EXPERIMENTAL DESIGN: Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretio...
Source: Clinical Cancer Research - April 15, 2019 Category: Cancer & Oncology Authors: Leighl NB, Page RD, Raymond VM, Daniel DB, Divers SG, Reckamp KL, Villalona-Calero MA, Dix D, Odegaard JI, Lanman RB, Papadimitrakopoulou VA Tags: Clin Cancer Res Source Type: research

Phase I study of intermittent high dose lapatinib alternating with capecitabine for HER2-positive breast cancer patients with central nervous system metastases.
CONCLUSIONS: High dose lapatinib is tolerable when given intermittently and sequentially with capecitabine. Antitumor activity was noted in both CNS and non-CNS sites of disease. This novel administration regimen is feasible and efficacious in HER2-positive breast cancer patients with CNS metastasis and warrants further investigation. PMID: 30988080 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2019 Category: Cancer & Oncology Authors: Morikawa A, de Stanchina E, Pentsova E, Kemeny MM, Li BT, Tang K, Patil S, Fleisher M, Van Poznak C, Norton L, Seidman AD Tags: Clin Cancer Res Source Type: research

Tumor-associated macrophages as prognostic and predictive biomarkers for postoperative adjuvant chemotherapy in patients with stage II colon cancer.
CONCLUSIONS: For stage II colon cancer, CD206/CD68 ratio is a better prognostic and predictive biomarker for postoperative adjuvant chemotherapy. Together with clinicopathological high-risk factors, it will aid in precision treatment. PMID: 30988081 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2019 Category: Cancer & Oncology Authors: Feng Q, Chang W, Mao Y, He G, Zheng P, Tang W, Wei Y, Ren L, Zhu D, Ji M, Tu Y, Qin X, Xu JM Tags: Clin Cancer Res Source Type: research

Detection of NRG1 gene fusions in solid tumors.
CONCLUSION: NRG1 fusions can be detected at a low incidence across multiple tumor types with significant heterogeneity in fusion partner. PMID: 30988082 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2019 Category: Cancer & Oncology Authors: Jonna S, Feldman RA, Swensen J, Gatalica Z, Korn WM, Borghaei H, Ma PC, Nieva JJ, Spira AI, VanderWalde AM, Wozniak AJ, Kim ES, Liu SV Tags: Clin Cancer Res Source Type: research

Correction: Epigenetic Therapy with Panobinostat Combined with Bicalutamide Rechallenge in Castration-Resistant Prostate Cancer.
PMID: 30988096 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2019 Category: Cancer & Oncology Authors: Ferrari AC, Alumkal JJ, Stein MN, Taplin ME, Babb J, Barnett ES, Gomez-Pinillos A, Liu X, Moore D, DiPaola R, Beer TM Tags: Clin Cancer Res Source Type: research

Correction: Simultaneous Expression of Furin and Vascular Endothelial Growth Factor in Human Oral Tongue Squamous Cell Carcinoma Progression.
PMID: 30988097 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2019 Category: Cancer & Oncology Authors: de Cicco RL, Watson JC, Bassi DE, Litwin S, Klein-Szanto AJ Tags: Clin Cancer Res Source Type: research

Correction: Inhibition of Furin-mediated Processing Results in Suppression of Astrocytoma Cell Growth and Invasiveness.
PMID: 30988098 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2019 Category: Cancer & Oncology Authors: Mercapide J, De Cicco RL, Bassi DE, Castresana JS, Thomas G, Klein-Szanto AJP Tags: Clin Cancer Res Source Type: research

Retraction: FRA-1 Expression in Hyperplastic and Neoplastic Thyroid Diseases.
PMID: 30988099 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2019 Category: Cancer & Oncology Authors: Chiappetta G, Tallini G, De Biasio MC, Pentimalli F, de Nigris F, Losito S, Fedele M, Battista S, Verde P, Santoro M, Fusco A Tags: Clin Cancer Res Source Type: research

Precision Targeting with EZH2 and HDAC Inhibitors in Epigenetically Dysregulated Lymphomas.
CONCLUSIONS: Inhibition of EZH2 and HDAC is synergistic and leads to the dissociation of PRC2 complex. Our findings support the clinical translation of the combination of EZH2 and HDAC inhibition in EZH2 dysregulated lymphomas. PMID: 30979734 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Lue JK, Prabhu SA, Liu Y, Gonzalez Y, Verma A, Mundi PS, Abshiru NA, Camarillo JM, Mehta S, Chen EI, Qiao C, Nandakumar R, Cremers S, Kelleher NL, Elemento O, Amengual JE Tags: Clin Cancer Res Source Type: research

Combined CD28 and 4-1BB costimulation potentiates affinity-tuned Chimeric Antigen Receptor-engineered T cells.
Abstract PURPOSE: Targeting non-specific, tumor associated antigens (TAA) with chimeric antigen receptors (CARs) requires specific attention to restrict possible detrimental on-target/off-tumor effects. A reduced affinity may direct CAR-engineered T (CAR-T) cells to tumor cells expressing high TAA levels while sparing low expressing normal tissues. However, decreasing the affinity of the CAR-target binding may compromise the overall anti-tumor effects. Here, we demonstrate the prime importance of the type of intracellular signaling on the function of low affinity CAR-T cells. EXPERIMENTAL DESIGN: We used a se...
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Drent E, Poels R, Ruiter R, van de Donk NWCJ, Zweegman S, Yuan H, de Bruijn J, Sadelain M, Lokhorst HM, Groen R, Mutis T, Themeli M Tags: Clin Cancer Res Source Type: research

A Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab followed by Bevacizumab Monotherapy in Patients with Advanced Kaposi Sarcoma.
CONCLUSIONS: Pegylated liposomal doxorubicin in combination with bevacizumab has activity in advanced KS, but it is unclear if the combination yields better outcomes than liposomal doxorubicin used alone. PMID: 30979736 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Ramaswami R, Uldrick TS, Polizzotto MN, Wyvill KM, Goncalves P, Widell A, Lurain K, Steinberg SM, Figg WD, Tosato G, Whitby D, Yarchoan R Tags: Clin Cancer Res Source Type: research

Activity and Safety of Palbociclib in Patients with Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib: A Biomarker-driven Phase 2 study.
CONCLUSION: Palbociclib has no significant clinical activity as a single agent in P16/CDKN2A deleted GIST refractory to Imatinib and Sunitinib. PMID: 30979737 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Toulmonde M, Bellera CA, Blay JY, Bouche O, Mir O, Penel N, Isambert N, Duffaud F, Esnaud T, Boidot R, Geneste D, Ghiringhelli F, Lucchesi C, Le Loarer F, Italiano A Tags: Clin Cancer Res Source Type: research

IL-23-producing human lung cancer cells promote tumor growth via conversion of innate lymphoid cell 1 (ILC1) into ILC3.
CONCLUSIONS: Conversion from ILC1 into ILC3 by IL-23-producing SqCCs promotes IL-17-mediated tumor progression, resulting in a poor prognosis. PMID: 30979738 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Koh J, Kim HY, Lee Y, Park IK, Kang CH, Kim YT, Kim JE, Choi M, Lee WW, Jeon YK, Chung DH Tags: Clin Cancer Res Source Type: research

Non-canonical TGFb pathway relieves the blockade of IL-1b/TGFb-mediated crosstalk between tumour and stroma: TGFBR1TAK1 inhibition in colorectal cancer.
CONCLUSION: Our findings provide a translational rationale for the inhibition of TAK1 and TGFBR1 to remove the chemoprotection conferred by CAFs. PMID: 30979739 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Díaz-Maroto NG, Sanz-Pamplona R, Berdiel-Acer M, Cimas FJ, García E, Gonçalves-Ribeiro S, Albert N, Garcia-Vicién G, Capella G, Moreno V, Salazar R, Villanueva A, Mollevi DG Tags: Clin Cancer Res Source Type: research

Mutational diversity and therapy response in breast cancer - a sequencing analysis in the neoadjuvant GeparSepto trial.
a V, Untch M, Carsten D Abstract PURPOSE: Next-generation-sequencing (NGS) can be used for comprehensive investigation of molecular events in breast cancer (BC). We evaluated the relevance of genomic alterations for response to neoadjuvant chemotherapy (NACT) in the GeparSepto trial. EXPERIMENTAL DESIGN: 851 pretherapeutic FFPE core biopsies from GeparSepto study were sequenced. The panel included 16 genes for mutational (AKT1, BRAF, CDH1, EGFR, ERBB2, ESR1, FBXW7, FGFR2, HRAS, KRAS, NRAS, SF3B1, TP53, HNF1A, PIK3CA, PTEN) and 8 genes for copy number alteration analysis (CCND1, ERBB2, FGFR1, PAK1, PIK3CA, TOP...
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Loibl S, Treue D, Budczies J, Weber K, Stenzinger A, Schmitt WD, Weichert W, Jank P, Furlanetto J, Klauschen F, Karn T, Pfarr N, von Minckwitz G, Möbs M, Jackisch C, Sers C, Scneeweiss A, Fasching PA, Schem C, Hummel M, van Mackelenbergh MT, Nekljudova V Tags: Clin Cancer Res Source Type: research

Profiling the mutational landscape in known driver genes and novel genes in African American non-small cell lung cancer patients.
Abstract PURPOSE: Identifying novel driver genes and mutations in African American non-small cell lung cancer (NSCLC) cases can inform targeted therapy and improve outcomes for this traditionally under-represented population. EXPERIMENTAL DESIGN: Tumor DNA, RNA and germline DNA was collected from African American NSCLC patients who participated in research conducted at the Karmanos Cancer Institute (KCI) in Detroit, MI. Known mutations were ascertained through the Sequenom LungCarta panel of 214 mutations in 26 genes, RET/ROS1 fusions, amplification of FGFR1, and expression of ALK. Paired tumor and normal DNA...
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Lusk CM, Watza D, Dyson G, Craig DB, Ratliff V, Wenzlaff AS, Lonardo F, Bollig-Fischer A, Bepler G, Purrington KS, Gadgeel S, Schwartz AG Tags: Clin Cancer Res Source Type: research

Antibody Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index.
Abstract Since the first approval of gemtuzumab ozogamicin (Mylotarg; CD33 targeted), 2 additional antibody drug conjugates (ADCs)-brentuximab vedotin (Adcetris; CD30 targeted) and inotuzumab ozogamicin (Besponsa; CD22 targeted)-have been approved for hematologic cancers and 1 ADC, trastuzumab emtansine (Kadcyla; HER2 targeted), has been approved to treat breast cancer. Despite a clear clinical benefit being demonstrated for all 4 approved ADCs, the toxicity profiles are comparable to those of standard-of-care chemotherapeutics, with dose-limiting toxicities associated with the mechanism of activity of the cytotox...
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Coats S, Williams M, Kebble B, Dixit R, Tseng L, Yao NS, Tice DA, Soria JC Tags: Clin Cancer Res Source Type: research

Proteomics derived biomarker panel improves diagnostic precision to classify endometrioid and high-grade serous ovarian carcinoma.
l M Abstract PURPOSE: Ovarian carcinomas are a group of distinct diseases classified by histotypes. As histotype-specific treatment evolves, accurate classification will become critical for optimal precision medicine approaches. EXPERIMENTAL DESIGN: To uncover differences between the two most common histotypes - high-grade serous (HGSC) and endometrioid carcinoma (EC) - we performed label-free quantitative proteomics on freshly frozen tumour tissues (HGSC, n=10; EC, n=10). Eight candidate protein biomarkers specific to EC were validated by immunohistochemistry using tissue microarrays representing 361 cases o...
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Postovit LM, Dieters-Castator DZ, Rambau PF, Kelemen LE, Siegers GM, Lajoie GA, Köbel M Tags: Clin Cancer Res Source Type: research

Genome-wide RNAi screening identifies RFC4 as a factor that mediates radioresistance in colorectal cancer by facilitating non-homologous end joining repair.
CONCLUSIONS: RFC4 was identified as a radioresistance factor that promotes NHEJ-mediated DNA repair in CRC cells. Additionally, the expression level of RFC4 predicted radiotherapy responsiveness and the outcome of neoadjuvant radiotherapy in LARC patients. PMID: 30979744 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Wang XC, Yue X, Zhang R, Liu TY, Pan Z, Yang MJ, Lu Z, Wang ZY, Peng J, Le LY, Wang G, Peng Q, Meng Y, Huang W, Liu RY Tags: Clin Cancer Res Source Type: research

High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma.
CONCLUSIONS: FAK and Aurora kinase B inhibitors synergistically impair Ewing sarcoma cell viability and significantly inhibit tumor progression. This study provides preclinical support for the consideration of a clinical trial testing the safety and efficacy of this combination for patients with Ewing sarcoma. PMID: 30979745 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 12, 2019 Category: Cancer & Oncology Authors: Wang S, Hwang EE, Guha R, O'Neill AF, Melong N, Veinotte CJ, Saur Conway A, Wuerthele K, Shen M, McKnight C, Alexe G, Lemieux ME, Wang A, Hughes E, Xu X, Boxer MB, Hall MD, Kung AL, Berman JN, Davis MI, Stegmaier K, Crompton BD Tags: Clin Cancer Res Source Type: research

Application of Artificial Intelligence for Preoperative Diagnostic and Prognostic Prediction in Epithelial Ovarian Cancer Based on Blood Biomarkers.
Conclusions: Machine learning systems can provide critical diagnostic and prognostic prediction for patients with EOC before initial intervention, and the use of predictive algorithms may facilitate personalized treatment options through pretreatment stratification of patients. PMID: 30979733 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 11, 2019 Category: Cancer & Oncology Authors: Kawakami E, Tabata J, Yanaihara N, Ishikawa T, Koseki K, Iida Y, Saito M, Komazaki H, Shapiro JS, Goto C, Akiyama Y, Saito R, Saito M, Takano H, Yamada K, Okamoto A Tags: Clin Cancer Res Source Type: research

PI3K/AKT/mTOR pathway alterations promote malignant progression and xenograft formation in oligodendroglial tumors.
Ryo A, Yamanaka S, Curry WT, Dias-Santagata D, Yamamoto T, Ichimura K, Batchelor T, Chi AS, Iafrate AJ, Wakimoto H, Cahill DP Abstract PURPOSE: Oligodendroglioma (OD) has a relatively favorable prognosis, however, often undergoes malignant progression. We hypothesized that preclinical models of OD could facilitate identification of therapeutic targets in progressive OD. We established multiple OD xenografts to determine if PI3K/AKT/mTOR signaling pathway drives tumor progression. EXPERIMENTAL DESIGN: Two anatomically distinct tumor samples from a patient who developed progressive anaplastic oligodendroglioma...
Source: Clinical Cancer Research - April 11, 2019 Category: Cancer & Oncology Authors: Tateishi K, Nakamura T, Juratli TA, Williams EA, Matsushita Y, Miyake S, Nishi M, Miller JJ, Tummala SS, Fink AL, Lelic N, Koerner MVA, Miyake Y, Sasame J, Fujimoto K, Tanaka T, Minamimoto R, Matsunaga S, Mukaihara S, Shuto T, Taguchi H, Udaka N, Murata H Tags: Clin Cancer Res Source Type: research

Prognostic Value of Deep Learning PET/CT-based Radiomics: Potential Role for Future Individual Induction Chemotherapy in Advanced Nasopharyngeal Carcinoma.
Abstract PURPOSE: We aimed to evaluate the value of deep learning on PET/CT-based radiomics for individual induction chemotherapy (IC) in advanced nasopharyngeal carcinoma (NPC). EXPERIMENTAL DESIGN: We constructed radiomics signatures and nomogram for predicting disease-free survival (DFS) based on the extracted features from PET and CT images in training set (n=470), and then validated it on a test set (n=237). Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis were applied to evaluate the discriminatory ability of radiomics nomogram, and compare ra...
Source: Clinical Cancer Research - April 11, 2019 Category: Cancer & Oncology Authors: Peng H, Dong D, Fang M, Li L, Tang LL, Chen L, Li WF, Mao YP, Fan W, Liu LZ, Tian L, Lin AH, Sun Y, Tian J, Ma J Tags: Clin Cancer Res Source Type: research

Survival Following Chemotherapy in Ovarian Clear Cell Carcinoma is Not Associated with Pathological Misclassification of Tumor Histotype.
CONCLUSIONS: Survival benefit following chemotherapy in OCCC was not associated with pathological misclassification of tumor histotype. HNF1B loss may help identify the subset of patients with OCCC with a more favorable outcome. PMID: 30967419 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 9, 2019 Category: Cancer & Oncology Authors: Takenaka M, Köbel M, Garsed DW, Fereday S, Pandey A, Etemadmoghadam D, Hendley J, Kawabata A, Noguchi D, Yanaihara N, Takahashi H, Kiyokawa T, Ikegami M, Takano H, Isonishi S, Ochiai K, Traficante N, Gadipally SR, Semple T, Vassiliadis D, Amarasinghe KC, Tags: Clin Cancer Res Source Type: research

Association of Systemic Inflammation Index and Body Mass Index With Survival in Patients With Renal Cell Cancer Treated With Nivolumab.
ta C, Sternberg C Abstract PURPOSE: Inflammation indexes and body mass index (BMI) are easily evaluated, predict survival and are potentially modifiable. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of patients with renal cell carcinoma (RCC) undergoing immune checkpoint inhibitor therapy. EXPERIMENTAL DESIGN: A prospective cohort of patients with metastatic RCC treated with nivolumab enrolled in the Italian Expanded Access Program (EAP) from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil to lymph...
Source: Clinical Cancer Research - April 9, 2019 Category: Cancer & Oncology Authors: De Giorgi U, Procopio G, Giannarelli D, Sabbatini R, Bearz A, Buti S, Basso U, Mitterer M, Ortega C, Bidoli P, Ferraù F, Crinò L, Frassoldati A, Marchetti P, Mini E, Scoppola A, Verusio C, Fornarini G, Cartenì G, Caserta C, Sternberg C Tags: Clin Cancer Res Source Type: research

Class 1, 2 and 3 BRAF mutated metastatic colorectal cancer: a detailed clinical, pathological and molecular characterization.
ei Tos AP, De Maglio G, Martini M, Bergamo F, Zagonel V, Loupakis F, Fassan M Abstract Purpose BRAF mutations are grouped in activating RAS-independent signaling as monomers (class 1 - V600E) or as dimers (class 2 - codons 597/601), and RAS-dependent with impaired kinase activity (class 3 - codons 594/596). While clinical, pathological and molecular features of V600E BRAF mutated metastatic colorectal cancer (mCRC) are well known, limited data are available from the two other classes. Experimental Design Data from 117 BRAF (92 class 1, 12 class 2, and 13 class 3) mutated mCRC patients were collected. 540 BRAF wt m...
Source: Clinical Cancer Research - April 9, 2019 Category: Cancer & Oncology Authors: Schirripa M, Biason P, Lonardi S, Pella N, Pino MS, Urbano F, Antoniotti C, Cremolini C, Corallo S, Pietrantonio F, Gelsomino F, Cascinu S, Orlandi A, Munari G, Malapelle U, Saggio S, Fontanini G, Rugge M, Mescoli C, Lazzi S, Reggiani Bonetti L, Lanza G, Tags: Clin Cancer Res Source Type: research

Leukemia inhibitory factor promotes castration-resistant prostate cancer and neuroendocrine differentiation by activated ZBTB46.
CONCLUSIONS: Our findings suggest that LIF is a potent serum biomarker for diagnosing advanced prostate cancer and that targeting the ZBTB46-LIF axis may therefore inhibit CRPC development and NE differentiation after ADT. PMID: 30962287 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 8, 2019 Category: Cancer & Oncology Authors: Liu YN, Niu S, Chen WY, Zhang Q, Tao Y, Chen WH, Jiang KC, Chen X, Shi H, Liu A, Li J, Li Y, Lee YC, Zhang X, Huang J Tags: Clin Cancer Res Source Type: research

Therapeutic Targeting of Non-Oncogene Dependencies in High-Risk Neuroblastoma.
CONCLUSIONS: Our results establish a gene-expression-based strategy to interrogate cancer biology and inform drug discovery and repositioning for high-risk neuroblastoma. PMID: 30952635 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Huang CT, Hsieh CH, Lee WC, Liu YL, Yang TS, Hsu WM, Oyang YJ, Huang HC, Juan HF Tags: Clin Cancer Res Source Type: research

MicroRNA 31-3p expression and benefit from anti-EGFR inhibitors in metastatic colorectal cancer patients enrolled in the prospective phase II PROSPECT-C trial.
Conclusions: Our study validates the role of microRNA-31-3p as potential predictive biomarker of selection for anti-EGF mABs. PMID: 30952636 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Anandappa G, Lampis A, Cunningham D, Khan KH, Kouvelakis K, Vlachogiannis G, Hedayat S, Tunariu N, Rao S, Watkins D, Starling N, Braconi C, Darvish Damavandi M, Lote H, Thomas J, Peckitt C, Kalaitzaki E, Khan N, Fotiadis N, Rugge M, Begum R, Rana I, Bryan Tags: Clin Cancer Res Source Type: research

A novel autocrine CXCL14/ACKR2 axis: The Achilles' heel of cancer metastasis?
Abstract Cancer-associated fibroblasts (CAFs) are essential for cancer hallmarks. While CAFs are molecularly heterogeneous, a CXCL14-expressing subset has been a critical player in the cancer context. In breast cancer, an autocrine fibroblast CXCL14/ACKR2 axis mediates epithelial-to-mesenchymal transition (EMT) and endows metastatic traits, which offers novel therapeutic potential in the clinical setting. PMID: 30952637 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Zhang Q, Zhou N, Wang W, Zhou S Tags: Clin Cancer Res Source Type: research

Molecular characterization of neuroendocrine-like bladder cancer.
CONCLUSION: A single patient classifier was developed that identifies patients with histological urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC which may require different treatment. PMID: 30952638 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Batista da Costa J, Gibb EA, Bivalacqua TJ, Liu Y, Oo HZ, Miyamoto DT, Alshalalfa M, Davicioni E, Wright JL, Dall'Era M, Douglas J, Boormans JL, van der Heijden MS, Wu CL, van Rhijn BW, Gupta S, Grivas P, Mouw KW, Murugan P, Fazli L, Ra S, Konety BR, Seil Tags: Clin Cancer Res Source Type: research

First-in-Human Phase I Study of the Selective MET Inhibitor, Savolitinib, in Patients with Advanced Solid Tumors: Safety, Pharmacokinetics and Anti-Tumor Activity.
CONCLUSION: The tolerability profile of savolitinib was acceptable and the RP2D was established as 600 mg QD. Preliminary anti-tumor activity was demonstrated supporting further study in patients with PRCC. PMID: 30952639 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Gan HK, Millward MJ, Hua Y, Qi C, Sai Y, Su W, Wang J, Zhang L, Frigault MM, Morgan S, Yang L, Lickliter JD Tags: Clin Cancer Res Source Type: research

A Phase I/II Trial of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma.
CONCLUSIONS: This trial is the first to report outcomes using a triplet regimen of high-dose carfilzomib. KDD was well tolerated and appears efficacious in RRMM. Additional study is needed to more precisely determine patient outcomes with this regimen and its utility compared to other carfilzomib containing salvage regimens. PMID: 30952640 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Schroeder MA, Fiala MA, Huselton E, Cardone MH, Jaeger S, Jean SR, Shea K, Ghobadi A, Wildes T, Stockerl-Goldstein KE, Vij R Tags: Clin Cancer Res Source Type: research

About Face: Molecular Aberrations in Head and Neck Mucosal Melanomas.
Abstract Detailed molecular characterization of a large cohort of mucosal melanomas, most arising from head and neck primaries, suggests that chromosomal translocations and other complex rearrangements have prognostic importance. CDK4 amplification is a frequent event in these rare tumors, and CDK4/6 inhibition may represent a rational clinical trial strategy. PMID: 30952641 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Shoushtari AN Tags: Clin Cancer Res Source Type: research

Efficacy of combined VEGFR1-3, PDGF α/β, and FGFR1-3 blockade using nintedanib for esophagogastric cancer.
CONCLUSIONS: Nintedanib treatment resulted in modest disease stabilization in patients with metastatic esophagogastric cancer. Alterations in cell cycle pathway genes and increased global copy-number alteration burden warrant further study as prognostic or predictive biomarkers. PMID: 30952642 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Won E, Basunia A, Chatila WK, Hechtman JF, Chou JF, Ku GY, Chalasani SB, Boyar MS, Goldberg Z, Desai AM, Tuvy Y, Berger MF, Tang LH, Kelsen DP, Schattner M, Ilson DH, Capanu M, Solit DB, Schultz N, Janjigian YY Tags: Clin Cancer Res Source Type: research

Targeting High Mobility Group Box-1 (HMGB1) Promotes Cell Death in Myelodysplastic Syndrome.
CONCLUSIONS: Inhibition of HMGB1 could promote MDS cell death and alter innate immune responses via suppression of NFkB pathways. PMID: 30952643 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: Kam AYF, Piryani SO, McCall CM, Park HS, Rizzieri DA, Doan PL Tags: Clin Cancer Res Source Type: research

Clinical and Genome-Wide Analysis of Cisplatin-Induced Tinnitus Implicates Novel Ototoxic Mechanisms.
, Dolan ME Abstract PURPOSE: Cisplatin, a commonly used chemotherapeutic, results in tinnitus, the phantom perception of sound. Our purpose was to identify the clinical and genetic determinants of tinnitus among testicular cancer survivors (TCS) following cisplatin-based chemotherapy. EXPERIMENTAL DESIGN: TCS (n= 762) were dichotomized to cases (moderate/severe tinnitus; n=154) and controls (none; n=608). Logistic regression was used to evaluate associations with comorbidities and SNP dosages in GWAS following quality control and imputation (covariates: age, noise exposure, cisplatin dose, genetic principal c...
Source: Clinical Cancer Research - April 5, 2019 Category: Cancer & Oncology Authors: El Charif O, Mapes B, Trendowski MR, Wheeler HE, Wing C, Dinh PC, Frisina RD, Feldman DR, Hamilton R, Vaughn DJ, Fung C, Kollmannsberger C, Mushiroda T, Kubo M, Gamazon ER, Cox N, Huddart R, ArdeshirRouhaniFard S, Monahan P, Fossa SD, Einhorn LH, Travis L Tags: Clin Cancer Res Source Type: research

The Intersection Between Tumor Angiogenesis and Immune Suppression.
Abstract Both immune checkpoint inhibitors (ICIs) and anti-angiogenesis agents have changed the landscape of cancer treatment in the modern era. While anti-angiogenesis agents have demonstrated activities in tumors with high vascularization including renal cell carcinoma (RCC) and colorectal cancer (CRC), the effect of ICIs have been seen mainly in immunologically recognized tumors, with highly immune infiltrative lymphocytes. The main challenge in ICIs drug development is moving their activities to non-inflamed tumors and overcoming resistance that is driven in part by the immune suppressive microenvironment. Ang...
Source: Clinical Cancer Research - April 3, 2019 Category: Cancer & Oncology Authors: Rahma OE, Hodi FS Tags: Clin Cancer Res Source Type: research