Induction of peripheral effector CD8 T cell proliferation by combination of paclitaxel, carboplatin and bevacizumab in non-small cell lung cancer patients.
CONCLUSIONS: Paclitaxel/ carboplatin/ bevacizumab induces proliferation of CD8 T cells, consisting of effector cells expressing co-inhibitory checkpoint molecules. Induction of proliferation was not correlated to clinical outcome in the current clinical setting. Our findings provide a rationale for combining PCB with checkpoint inhibition in lung cancer. PMID: 30642911 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 14, 2019 Category: Cancer & Oncology Authors: de Goeje PL, Poncin M, Bezemer K, Kaijen-Lambers MEH, Groen HJ, Smit EF, Dingemans AC, Kunert A, Hendriks RW, Aerts JG Tags: Clin Cancer Res Source Type: research

Immunologic correlates of the abscopal effect in a SMARCB1/INI1-negative Poorly Differentiated Chordoma after EZH2 inhibition and radiotherapy.
CONCLUSIONS: These observations are the first demonstration in patient samples confirming that EZH2 inhibition can promote a sustained antitumor response that ultimately leads to T cell exhaustion and checkpoint activation. This suggests that targeted altering of the epigenetic landscape may sensitize some tumors to checkpoint inhibitors. PMID: 30642912 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 14, 2019 Category: Cancer & Oncology Authors: Gounder MM, Zhu G, Roshal L, Lis E, Daigle SR, Blakemore SJ, Michaud NR, Hameed M, Hollmann TJ Tags: Clin Cancer Res Source Type: research

Immunotherapy for the first-line treatment of patients with metastatic non-small cell lung cancer.
Abstract Immunotherapy has fundamentally changed the treatment landscape for many patients with cancer. Monoclonal antibodies targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 immune checkpoints have received regulatory approval across a wide range of tumor types, including non-small cell lung cancer (NSCLC). Indeed, treatment approaches for a majority of patients with newly diagnosed metastatic NSCLC are evolving rapidly. Only for the small proportion of patients with metastatic NSCLC and genomic-driven tumors with epidermal growth fac...
Source: Clinical Cancer Research - January 14, 2019 Category: Cancer & Oncology Authors: Martinez P, Peters S, Stammers T, Soria JC Tags: Clin Cancer Res Source Type: research

No Cell Left Unturned: Intraductal Papillary Mucinous Neoplasm Heterogeneity.
This study utilizes single cell RNA-seq to describe the dynamic landscape of epithelial, immune, and stromal cells during IPMN progression to invasive cancer. PMID: 30642914 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 14, 2019 Category: Cancer & Oncology Authors: Hernandez-Barco YG, Bardeesy N, Ting DT Tags: Clin Cancer Res Source Type: research

Combination Paclitaxel and Palbociclib: Results of a Phase I Trial in Advanced Breast Cancer.
CONCLUSIONS: Alternating sequential palbociclib/paclitaxel in patients with Rb+ ABC is feasible and safe, without evidence of additive toxicity. This represents a new application for CDK 4/6 inhibitors in Rb+ breast cancer, regardless of subtype; efficacy trials are warranted. PMID: 30635336 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 11, 2019 Category: Cancer & Oncology Authors: Clark AS, McAndrew NP, Troxel A, Feldman M, Lal P, Rosen M, Burrell J, Redlinger C, Gallgher M, Bradbury AR, Domchek SM, Fox KR, O'Dwyer PJ, DeMichele AM Tags: Clin Cancer Res Source Type: research

Autophagy inhibition to augment mTOR inhibition: A phase I/II trial of everolimus and hydroxychloroquine in patients with previously treated renal cell carcinoma.
Conclusion Combined HCQ 600mg twice daily with 10 mg daily everolimus was tolerable. The primary endpoint of>40% 6 month PFS rate was met. HCQ is a tolerable autophagy inhibitor in future RCC or other trials. PMID: 30635337 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 11, 2019 Category: Cancer & Oncology Authors: Haas NB, Appleman LJ, Stein M, Redlinger M, Wilks M, Xu X, Onorati A, Kalavacharla A, Kim T, Zhen CJ, Kadri S, Segal JP, Gimotty PA, Davis LE, Amaravadi RK Tags: Clin Cancer Res Source Type: research

Vaccine-induced memory CD8+ T cells provide clinical benefit in HER2 expressing breast cancer: a mouse to human translational study.
CONCLUSIONS: VRP-HER2 increased HER2-specific memory CD8 T cells and had anti-tumor effects in preclinical and clinical studies. The expansion of HER2-specific memory CD8 T cells in vaccinated patients was significantly correlated with increased PFS. Subsequent studies will seek to enhance T cell activity by combining with anti-PD-1. PMID: 30635338 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 11, 2019 Category: Cancer & Oncology Authors: Crosby EJ, Gwin WR, Blackwell K, Marcom PK, Chang S, Maecker HT, Broadwater G, Hyslop TM, Kim S, Rogatko A, Lubkov V, Snyder JC, Osada T, Hobeika A, Morse MA, Lyerly HK, Hartman ZC Tags: Clin Cancer Res Source Type: research

WNT/ β-catenin pathway activation correlates with immune exclusion across human cancers.
CONCLUSIONS: Activation of tumor-intrinsic WNT/β-catenin signaling is enriched in non-T cell-inflamed tumors. These data provide a strong rationale for development of pharmacologic inhibitors of this pathway with the aim of restoring immune cell infiltration and augmenting immunotherapy. PMID: 30635339 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 11, 2019 Category: Cancer & Oncology Authors: Luke JJ, Bao R, Sweis RF, Spranger S, Gajewski TF Tags: Clin Cancer Res Source Type: research

The Misclassification of Diffuse Gliomas: Rates and Outcomes.
CONCLUSIONS: Based on 1p/19q, IDH, ATRX, and p53, the misclassification rates of histologically-encoded oligodendrogliomas, astrocytomas, and glioblastomas are ~21-35%, ~6-9%, and ~9%, respectively; with significant clinical implications. Our findings suggest that when compared to historical histology-only classified data-in national registry, as well as, institutional databases-there is the potential for false-positive results in contemporary trials of molecularly-classified diffuse gliomas, which could contribute to a seemingly positive phase II trial (based on historical comparison) failing at the phase III stage. Criti...
Source: Clinical Cancer Research - January 11, 2019 Category: Cancer & Oncology Authors: Iorgulescu JB, Torre M, Harary M, Smith TR, Aizer AA, Reardon DA, Barnholtz-Sloan JS, Perry A Tags: Clin Cancer Res Source Type: research

PRMT5-mediated H4R3sme2 confers cell differentiation in Pediatric B-cell Precursor Acute Lymphoblastic Leukemia.
CONCLUSIONS: We demonstrate that enhanced PRMT5 promotes BCP-ALL leukemogenesis partially by the dysregulation of B cell lineage differentiation. H4R3sme2 and PRMT5 may serve as potential sensitive biomarkers of pediatric BCP-ALL. Suppression of the activation of PRMT5 and its downstream targets may offer a promising therapeutic strategy against pediatric BCP-ALL. PMID: 30635341 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 11, 2019 Category: Cancer & Oncology Authors: Mei M, Zhang R, Zhou Z, Ying Z, Wang J, Zhang H, Zheng H, Bao S Tags: Clin Cancer Res Source Type: research

Distinct Molecular Profiles and Immunotherapy Treatment Outcomes of V600E and V600K BRAF-Mutant Melanoma.
Conclusions: BRAF V600K melanomas appear to benefit less from BRAFi±MEKi than V600E, potentially due to less reliance on ERK pathway activation and greater use of alternative pathways. In contrast, these melanomas have higher mutational load and respond better to immunotherapy. PMID: 30630828 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 10, 2019 Category: Cancer & Oncology Authors: Pires da Silva I, Wang KYX, Wilmott JS, Holst J, Carlino MS, Park JJ, Quek C, Wongchenko M, Yan Y, Mann G, Johnson DB, McQuade JL, Rai R, Kefford RF, Rizos H, Scolyer RA, Yang JYH, Long GV, Menzies AM Tags: Clin Cancer Res Source Type: research

Mapping physical tumor microenvironment and drug delivery.
Abstract The physical microenvironment of pancreatic tumors is highly abnormal, and this causes significant challenges for drug delivery through multiple mechanisms. Measurements of tissue elasticity could be used as a physical biomarker to assess aberrant drug delivery, and potentially guide stroma-targeting treatment strategies and patient stratification. PMID: 30630829 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 10, 2019 Category: Cancer & Oncology Authors: Nia HT, Munn LL, Jain RK Tags: Clin Cancer Res Source Type: research

Low-Pass Whole-Genome Sequencing of Circulating Cell-Free DNA Demonstrates Dynamic Changes in Genomic Copy Number in a Squamous Lung Cancer Clinical Cohort.
CONCLUSION: LP-WGS offers an unbiased and high-throughput way to investigate CNVs and tumor fraction in cfDNA of cancer patients. It may also be valuable for monitoring treatment response, detecting disease progression early, and identifying emergent clones associated with therapeutic resistance. PMID: 30617129 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Chen X, Chang CW, Spoerke JM, Yoh K, Kapoor V, Baudo CD, Aimi J, Yu M, Liang-Chu MMY, Suttman R, Huw LY, Gendreau S, Cummings CA, Lackner MR Tags: Clin Cancer Res Source Type: research

Brentuximab Vedotin Plus Chemotherapy in North American Patients with Newly Diagnosed Stage III or IV Hodgkin Lymphoma.
CONCLUSIONS: The efficacy benefit and manageable toxicity profile observed in the NA subgroup of ECHELON-1 support A+AVD as a frontline treatment option for Stage III or IV cHL patients. PMID: 30617130 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Ramchandren R, Advani RH, Ansell SM, Bartlett NL, Chen R, Connors JM, Feldman T, Forero A, Friedberg JW, Gopal AK, Gordon LI, Kuruvilla J, Savage KJ, Younes A, Engley G, Manley TJ, Fenton K, Straus DJ Tags: Clin Cancer Res Source Type: research

Circulating microRNAs and PD-L1 tumor expression are associated with survival in advanced NSCLC patients treated with immunotherapy: a prospective study.
Abstract PURPOSE: Immune-checkpoint inhibitors (ICIs) have improved the survival of NSCLC patients. However, only a subset of patients benefit from ICIs, and the role of PD-L1 as predictive biomarker is still debated. A plasma immune-related microRNA-signature classifier (MSC) was established in lung cancer screening settings in order to identify the lethal form of the disease in early stages. In the present exploratory study, we tested the efficacy of the MSC as prognostic marker in advanced NSCLC patients treated with ICIs. EXPERIMENTAL DESIGN: The MSC risk level was prospectively assessed in a consecutive ...
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Boeri M, Milione M, Proto C, Signorelli D, Lo Russo G, Galeone C, Verri C, Mensah M, Centonze G, Martinetti A, Sottotetti E, Pastorino U, Garassino MC, Sozzi G Tags: Clin Cancer Res Source Type: research

The sTRA Plasma Biomarker: Blinded Validation of Improved Accuracy over CA19-9 in Pancreatic Cancer Diagnosis.
We examined sTRA and CA19-9 expression and secretion in panels of cell lines, patient-derived xenografts, and primary tumors. We developed candidate biomarkers from sTRA and CA19-9 in a training set of 147 plasma samples and used the panels to make case/control calls, based on predetermined thresholds, in a 50-sample validation set and a blinded, 147-sample test set. RESULTS: The sTRA glycan was produced and secreted by pancreatic tumors and models that did not produce and secrete CA19-9. Two biomarker panels improved upon CA19-9 in the training set, one optimized for specificity, which included CA19-9 and two version...
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Haab BB, Staal B, Barnett D, Hsueh P, He Z, Gao CF, Partyka K, Hurd MW, Singhi AD, Drake RR, Huang Y, Liu Y, Brand RE, Maitra A Tags: Clin Cancer Res Source Type: research

Multiplex quantitative analysis of tumor-infiltrating lymphocytes and immunotherapy outcome in metastatic melanoma.
CONCLUSION: Pretreatment lymphocytic infiltration is associated with anti-PD-1 response in metastatic melanoma. Quantitative TIL analysis has potential for application in digital precision immuno-oncology as an "indicative" companion diagnostic. PMID: 30617133 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Wong PF, Wei W, Smithy JW, Acs B, Toki MI, Blenman KR, Zelterman D, Kluger HM, Rimm DL Tags: Clin Cancer Res Source Type: research

Integrated Molecular Analysis of Undifferentiated Uterine Sarcomas Reveals Clinically Relevant Molecular Subtypes.
CONCLUSIONS: Molecular evaluation of UUS provides novel insights into the biology, prognosis, phenotype and possible treatment of these tumors. PMID: 30617134 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Binzer-Panchal A, Hardell E, Viklund B, Ghaderi M, Bosse T, Nucci MR, Lee CH, Hollfelder N, Corcoran P, Gonzalez-Molina J, Moyano-Galceran L, Bell DA, Schoolmeester JK, Måsbäck A, Kristensen GB, Davidson B, Lehti K, Isaksson A, Carlson JW Tags: Clin Cancer Res Source Type: research

NQO1-dependent, tumor-selective radiosensitization of non-small cell lung cancers.
CONCLUSION: Our data suggest that combination of sublethal doses of ß-lap and IR is a viable approach to selectively treat NQO1-overexpressing NSCLC and warrant a clinical trial using low-dose IR + ß-lapachone against patients with NQO1+ NSCLCs. PMID: 30617135 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Motea EA, Huang X, Singh N, Kilgore JA, Williams NS, Xie XJ, Gerber DE, Beg M, Bey EA, Boothman DA Tags: Clin Cancer Res Source Type: research

Eradication of neuroblastoma by T cells redirected with an optimized GD2-specific chimeric antigen receptor and interleukin-15.
CONCLUSION: Our results guide new therapeutic options for GD2.CAR-Ts in patients with NB, and CAR-T development for a broad range of solid tumors. PMID: 30617136 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Chen Y, Sun C, Landoni E, Metelitsa LS, Dotti G, Savoldo B Tags: Clin Cancer Res Source Type: research

Genomic Landscape of Pancreatic Adenocarcinoma in Younger vs Older Patients: Does Age Matter?
CONCLUSIONS: These exploratory analyses suggest that there may be somatic gene alterations within the population of early onset PDAC patients that involve unique cellular pathways compared with average onset PDAC. Former studies imply these cellular pathways may play a role in smoking-related PDAC carcinogenesis. Larger genomic datasets are warranted for future evaluation to extend these observations. PMID: 30617137 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Ben-Aharon I, Elkabets M, Pelossof R, Yu KH, Iacobuzio-Donahue CA, Leach SD, Lowery MA, Goodman KA, O'Reilly EM Tags: Clin Cancer Res Source Type: research

Immune exclusion-Wnt/CTNNB1 class predicts resistance to immunotherapies in HCC.
Abstract Next generation sequencing has provided information on actionable targets and biomarkers of response in oncology. In HCC, Wnt/CTNNB1 mutations characterize the immune excluded class (cold tumors) and might represent the biomarkers predicting resistance to immune checkpoint inhibitors. Large-scale validation of this data is needed to customize immunotherapy in advanced HCC. PMID: 30617138 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Pinyol R, Sia D, Llovet JM Tags: Clin Cancer Res Source Type: research

Efficacy & Safety of Biosimilar ABP 215 Compared with Bevacizumab in Patients with Advanced Non-small Cell Lung Cancer(MAPLE):A Randomized,Double-blind,Phase 3 Study.
CONCLUSIONS: ABP 215 is similar to bevacizumab RP with respect to clinical efficacy, safety, immunogenicity, and pharmacokinetics. The totality of evidence supports clinical equivalence of ABP 215 and bevacizumab. PMID: 30617139 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Thatcher N, Goldschmidt JH, Thomas M, Schenker M, Pan Z, Paz-Ares L, Breder V, Ostoros G, Hanes V Tags: Clin Cancer Res Source Type: research

Developing allogeneic double negative T cells as a novel off-the-shelf adoptive cellular therapy for cancer.
CONCLUSION: We have established a method to generate therapeutic numbers of clinical-grade DNTs that fulfill the requirements of an off-the-shelf ACT. PMID: 30617140 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2019 Category: Cancer & Oncology Authors: Lee JB, Kang H, Fang L, D'Souza C, Adeyi O, Zhang L Tags: Clin Cancer Res Source Type: research

Exosome-Transmitted PSMA3 and PSMA3-AS1 Promotes Proteasome Inhibitors Resistance in Multiple Myeloma.
CONCLUSION: This study suggested a unique role of exosomal PSMA3 and PSMA3-AS1 in transmitting PIs resistance from MSCs to MM cells, through a novel exosomal PSMA3-AS1/PSMA3 signaling pathway. Exosomal PSMA3 and PSMA3-AS1 might act as promising therapeutic targets for PIs resistance and prognostic predictors for clinical response. PMID: 30610101 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2019 Category: Cancer & Oncology Authors: Xu H, Han H, Song S, Yi N, Qian C, Qiu Y, Zhou W, Hong Y, Zhuang W, Li Z, Li B, Zhuang W Tags: Clin Cancer Res Source Type: research

TP53 and prognosis in mCRPC Survival: Biology or Coincidence?
Abstract Cell-free circulating tumour DNA (ctDNA) or circulating tumour cell (CTC) assays are potentially powerful in the treatment of metastatic castration-resistant prostate cancer (mCRPC). A new study suggests that mutation of TP53 supercedes AR in predicting mCRPC survival. A role for TP53 mutation as a driver for mCRPC remains unexplored. PMID: 30610102 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2019 Category: Cancer & Oncology Authors: Rebello RJ, Oing C, Gillessen S, Bristow RG Tags: Clin Cancer Res Source Type: research

CKAP4, a DKK1 receptor, is a biomarker in exosomes derived from pancreatic cancer and a molecular target for therapy.
CONCLUSIONS: CKAP4 secreted in exosomes may represent a biomarker for PDAC. Anti-CKAP4 mAbs can contribute to the development of novel diagnostic methods and therapeutics. PMID: 30610103 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 4, 2019 Category: Cancer & Oncology Authors: Kimura H, Yamamoto H, Harada T, Fumoto K, Osugi Y, Sada R, Maehara N, Hikita H, Mori S, Eguchi H, Ikawa M, Takehara T, Kikuchi A Tags: Clin Cancer Res Source Type: research

Central Nervous System Metastasis in Patients With HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival From SystHERs.
Conclusions Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice. PMID: 30593513 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 28, 2018 Category: Cancer & Oncology Authors: Hurvitz SA, O'Shaughnessy J, Mason G, Yardley D, Jahanzeb M, Brufsky AM, Rugo HS, Swain SM, Kaufman PA, Tripathy D, Chu L, Li H, Antao V, Cobleigh M Tags: Clin Cancer Res Source Type: research

TAp73 modifies metabolism and positively regulates growth of cancer stem-like cells in a redox-sensitive manner.
CONCLUSION: Collectively, we reveal a clinically relevant aspect of cancer cell growth and stemness regulation through TAp73-mediated redox-sensitive metabolic reprogramming. PMID: 30593514 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 28, 2018 Category: Cancer & Oncology Authors: Sharif T, Dai C, Martell E, Saleh M, Hanes M, Murphy P, Kennedy B, Venugopal C, Subapanditha MK, Giacomantonio CA, Marcato P, Singh SK, Gujar S Tags: Clin Cancer Res Source Type: research

Mutational analysis of 472 urothelial carcinoma across grades and anatomic sites.
Abstract PURPOSE: Characterize the mutational landscape across the spectrum of urothelial carcinoma (UC) to identify mutational features and potential therapeutic targets. EXPERIMENTAL DESIGN: Using targeted exome sequencing (n=237 genes), we analyzed the mutation spectra of 82 low-grade non-muscle-invasive bladder cancers (LG-NMIBC), 126 high-grade (HG) NMIBC, 199 muscle-invasive bladder cancers (MIBC), 10 LG-upper tract urothelial cancers (LG-UTUC), and 55 HG-UTUC. RESULTS: FGFR3 and KDM6A mutations were significantly more common in LG-NMIBC (72% and 44%, respectively) versus other bladder subtypes. FG...
Source: Clinical Cancer Research - December 28, 2018 Category: Cancer & Oncology Authors: Nassar AH, Umeton R, Kim J, Lundgren K, Harshman LC, Van Allen EM, Preston MA, Dong F, Bellmunt J, Mouw KW, Choueiri TK, Sonpavde G, Kwiatkowski DJ Tags: Clin Cancer Res Source Type: research

Elevated WBP2 expression in HER2-positive breast cancers correlates with sensitivity to trastuzumab-based neo-adjuvant therapy:A Retrospective and Multicentric Study.
CONCLUSIONS: WBP2 expression correlates with the response of HER2-positive breast cancer to trastuzumab-based neoadjuvant chemotherapy. PMID: 30593516 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 28, 2018 Category: Cancer & Oncology Authors: Kang SA, Guan JS, Tan HJ, Chu T, Thike AA, Bernadó Morales C, Arribas J, Wong CY, Tan PH, Gudi M, Putti TC, Sohn J, Lim SH, Lee SC, Lim YP Tags: Clin Cancer Res Source Type: research

AR Variant Positive CTC: A Surrogate for a Surrogate for Taxane Therapy Outcome?
Abstract CTCs biomarkers may become indicators for selection of therapy. The presence of AR variant positive CTCs may be markers indicating need for switching therapy. Methods for AR variant mRNA isolation from CTCs and confirmation of expression are critical factors needed for these techniques to be clinically applicable. PMID: 30591516 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 27, 2018 Category: Cancer & Oncology Authors: Dehm SM, Montgomery B, Plymate SR Tags: Clin Cancer Res Source Type: research

SMAD4 loss in colorectal cancer patients correlates with recurrence, loss of immune infiltrate, and chemoresistance.
Cercek A, Ganesh K, Kemeny NE, Dhawan P, Yaeger R, Sawyers CL, Garcia-Aguilar J, Giannakis M, Shia J, Smith JJ Abstract PURPOSE: SMAD4 has shown promise in identifying patients with colorectal cancer (CRC) at high risk of recurrence or death. EXPERIMENTAL DESIGN: A discovery cohort and independent validation cohort were classified by SMAD4 status. SMAD4 status and immune infiltrate measurements were tested for association with recurrence-free survival (RFS). Patient-derived xenografts from SMAD4-deficient and SMAD4-retained tumors were used to examine chemoresistance. RESULTS: The discovery cohort consis...
Source: Clinical Cancer Research - December 26, 2018 Category: Cancer & Oncology Authors: Wasserman I, Lee LH, Ogino S, Marco MR, Wu C, Chen X, Datta J, Sadot E, Szeglin B, Guillem J, Paty PB, Weiser MR, Nash GM, Saltz L, Barlas A, Manova K, Uppada SB, Elghouayel AE, Ntiamoah P, Glickman JN, Hamada T, Kosumi K, Inamura K, Chan AT, Nishihara R, Tags: Clin Cancer Res Source Type: research

Dynamic contrast-enhanced MRI detects responses to stroma-directed therapy in mouse models of pancreatic ductal adenocarcinoma.
Abstract PURPOSE: The dense stroma underlies the drug resistance of pancreatic ductal adenocarcinoma (PDA) and has motivated the development of stroma-directed drugs. Our objective is to test the concept that dynamic contrast-enhanced (DCE) MRI using FDA-approved contrast media, an imaging method sensitive to the tumor microenvironment, can detect early responses to stroma-directed drug. EXPERIMENTAL DESIGN: Imaging studies were performed in three mouse models exhibiting high desmoplastic reactions: the autochthonous PDA in genetically engineered mice (KPC), an orthotopic model in syngeneic mice and a xenogra...
Source: Clinical Cancer Research - December 26, 2018 Category: Cancer & Oncology Authors: Cao J, Pickup S, Clendenin C, Blouw B, Choi H, Kang D, Rosen M, O'Dwyer PJ, Zhou R Tags: Clin Cancer Res Source Type: research

An Epithelial-to-Mesenchymal transcriptional switch triggers evolution of Pulmonary Sarcomatoid Carcinoma (PSC) and identifies dasatinib as new therapeutic option.
Conclusions: Our data provide new insights into PSC evolution and provide the rationale for further clinical studies with dasatinib. PMID: 30587547 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 26, 2018 Category: Cancer & Oncology Authors: Manzotti G, Torricelli F, Donati B, Lococo F, Sancisi V, Rossi G, Piana S, Ciarrocchi A Tags: Clin Cancer Res Source Type: research

Biomarkers for immunotherapy toxicity: are cytokines the answer?
Abstract Immune checkpoint inhibitors induce durable responses in some advanced cancer patients, but may simultaneously trigger auto-inflammatory immune-related adverse events (irAEs). The pathogenesis of irAEs may relate to genetic predisposition, environmental insults, or tumor-host interactions. Elevated expression of certain cytokines may signal subclinical inflammation that evolves into severe irAEs with treatment. PMID: 30587548 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 26, 2018 Category: Cancer & Oncology Authors: Johnson DB, Balko JM Tags: Clin Cancer Res Source Type: research

Epigenetic silencing of miRNA-338-5p and miRNA-421 drives SPINK1-positive prostate cancer.
CONCLUSION: Our findings revealed that miRNA-338-5p/-421 are epigenetically silenced in SPINK1-positive PCa, while restoring the expression of these miRNAs using epigenetic drugs or synthetic mimics could abrogate SPINK1-mediated oncogenesis. PMID: 30587549 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 26, 2018 Category: Cancer & Oncology Authors: Bhatia V, Yadav A, Tiwari R, Nigam S, Goel S, Carskadon S, Gupta N, Goel A, Palanisamy N, Ateeq B Tags: Clin Cancer Res Source Type: research

A Pilot Trial of the Combination of Transgenic NY-ESO-1-reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination With or Without Ipilimumab.
CONCLUSIONS: ACT of fresh NY-ESO-1 transgenic T cells prepared via a short ex vivo protocol and given with DC vaccination, with or without ipilimumab, is feasible and results in transient antitumor activity, with no apparent clinical benefit of the addition of ipilimumab. Improvements are needed to maintain tumor responses. PMID: 30573690 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 20, 2018 Category: Cancer & Oncology Authors: Nowicki TS, Berent-Maoz B, Cheung-Lau GC, Huang RR, Wang X, Tsoi J, Kaplan-Lefko PJ, Cabrera P, Tran J, Pang J, Macabali MH, Perez Garcilazo I, Baselga Carretero I, Kalbasi A, Cochran AJ, Grasso CS, Hu-Lieskovan S, Chmielowski B, Comin-Anduix B, Singh AS, Tags: Clin Cancer Res Source Type: research

Clinical and Genomic Implications of Luminal and Basal Subtypes Across Carcinomas.
CONCLUSIONS: This first pan-carcinoma luminal/basal subtyping across epithelial tumors reveals global similarities across carcinomas in the transcriptome, genome, clinical outcomes, and drug sensitivity, emphasizing the biological and translational importance of these luminal vs. basal subtypes. PMID: 30573691 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 20, 2018 Category: Cancer & Oncology Authors: Zhao SG, Chen WS, Das R, Chang SL, Tomlins SA, Chou J, Quigley DA, Dang HX, Barnard TJ, Mahal BA, Gibb EA, Liu Y, Davicioni E, Duska LR, Posadas EM, Jolly S, Spratt DE, Nguyen PL, Maher CA, Small EJ, Feng FY Tags: Clin Cancer Res Source Type: research

Molecular Classification of Lymph Node Metastases Subtypes Predict for Survival in Head and Neck Cancer.
CONCLUSIONS: The transcriptional profiles of LNMs better predict outcomes than transcriptional profiles of primary tumors. The LNMs display site-specific subtypes associated with worse disease control and survival across multiple cancer types. PMID: 30573692 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 20, 2018 Category: Cancer & Oncology Authors: Huang L, David O, Cabay RJ, Valyi-Nagy K, Macias V, Zhong R, Wenig B, Feldman L, Weichselbaum RR, Spiotto MT Tags: Clin Cancer Res Source Type: research

Tumor infiltrating lymphocytes - location for prognostic evaluation.
Abstract Tumor infiltrating lymphocytes (TIL) are crucial for the success of immunotherapy and their density can predict prognosis. It has now been shown that computer-based analysis of the spatial organization of TIL adds prognostic value in early-stage non-small cell lung cancer, possibly improving the treatment algorithm to prevent recurrence. PMID: 30567833 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 19, 2018 Category: Cancer & Oncology Authors: Peled M, Onn A, Herbst RS Tags: Clin Cancer Res Source Type: research

A Phase II Study of Talazoparib After Platinum or Cytotoxic Nonplatinum Regimens in Patients With Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO).
CONCLUSIONS: Talazoparib exhibited promising antitumor activity in patients with aBC and germline BRCA mutation. PMID: 30563931 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 18, 2018 Category: Cancer & Oncology Authors: Turner NC, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmaña J, Fasching PA, Hurvitz SA, Wardley AM, Chappey C, Hannah AL, Robson ME Tags: Clin Cancer Res Source Type: research

PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a multi-center, randomized double-blind, placebo-controlled phase 3 trial.
CONCLUSIONS: Short-term treatment with standard diabetic doses of metformin does not reduce tumor proliferation in women with endometrioid endometrial cancer awaiting hysterectomy. This study does not support a biological effect of metformin in endometrial cancer and casts doubt on its potential application in the primary and adjuvant treatment settings. PMID: 30563932 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 18, 2018 Category: Cancer & Oncology Authors: Kitson S, Maskell Z, Sivalingam VN, Allen JL, Ali S, Burns S, Gilmour K, Latheef R, Slade RJ, Pemberton P, Shaw J, Ryder WD, Kitchener HC, Crosbie EJ Tags: Clin Cancer Res Source Type: research

YAP1-mediated CDK6 Activation Confers Radiation Resistance in Esophageal Cancer - Rationale for the combination of YAP1 and CDK4/6 inhibitors in Esophageal Cancer.
CONCLUSIONS: Our results document that a positive crosstalk of YAP1 and CDK6 confers radiation resistance to EC cells. Targeting both YAP1 and CDK6 pathways could be novel therapeutic strategies to overcome resistance in EC. PMID: 30563933 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 18, 2018 Category: Cancer & Oncology Authors: Li F, Xu Y, Liu B, Singh PK, Zhao W, Jin J, Han G, Scott AW, Dong X, Huo L, Ma L, Pool Pizzi M, Wang Y, Li Y, Harada K, Xie M, Skinner HD, Ding S, Wang L, Krishnan S, Johnson RL, Song S, Ajani JA Tags: Clin Cancer Res Source Type: research

Phase IB Dose-Escalation and Expansion Study of AKT kinase inhibitor Afuresertib with Carboplatin and Paclitaxel in Recurrent Platinum-Resistant Ovarian Cancer.
Abstract PURPOSE: Preclinically, AKT kinase inhibition restores drug sensitivity in platinum-resistant tumors.Here the pan-AKT kinase inhibitor afuresertib was given in combination with paclitaxel and carboplatin (PC) in patients with recurrent platinum-resistant epithelial ovarian cancer (PROC) and primary platinum refractory ovarian cancer (PPROC). EXPERIMENTAL DESIGN: Part I was a combination 3+3 dose-escalation study for recurrent ovarian cancer. Patients received daily continuous oral afuresertib at 50-150 mg/day with three-weekly intravenous paclitaxel (175 mg/m2) and carboplatin (AUC5) for 6 cycles fol...
Source: Clinical Cancer Research - December 18, 2018 Category: Cancer & Oncology Authors: Blagden SP, Hamilton AL, Mileshkin L, Wong S, Michael A, Hall M, Goh JC, Lisyanskaya AS, DeSilvio M, Frangou E, Stronach EA, Gopalakrishna P, Meniawy TM, Gabra H Tags: Clin Cancer Res Source Type: research

Broad spectrum activity of the checkpoint kinase 1 inhibitor prexasertib as a single agent or chemopotentiator across a range of preclinical pediatric tumor models.
CONCLUSION: Prexasertib has significant anti-tumor effects as a monotherapy or in combination with chemotherapy in multiple preclinical models of pediatric cancer. These findings support further investigation of prexasertib in pediatric malignancies. PMID: 30563935 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 18, 2018 Category: Cancer & Oncology Authors: Lowery CD, Dowless M, Renschler M, Blosser W, VanWye AB, Stephens JR, Iversen PW, Bence Lin A, P Beckmann R, Krytska K, Cole KA, Maris JM, Hawkins DS, Rubin BP, Kurmasheva RT, Houghton PJ, Gorlick R, Kolb EA, Kang MH, Reynolds CP, Erickson SW, Teicher BA, Tags: Clin Cancer Res Source Type: research

Nuclear-cytoplasmic transport is a therapeutic target in myelofibrosis.
CONCLUSIONS: Our data implicate NCT as a potential therapeutic target in MF and provide a rationale for clinical evaluation in ruxolitinib exposed MF patients. PMID: 30563936 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 18, 2018 Category: Cancer & Oncology Authors: Yan D, Pomicter AD, Tantravahi S, Mason CC, Senina AV, Ahmann JM, Wang Q, Than H, Patel AB, Heaton W, Eiring AM, Clair PM, Gantz KC, Redwine HM, Swierczek SI, Halverson BJ, Baloglu E, Shacham S, Khorashad JS, Kelley TW, Salama ME, Miles RR, Boucher KM, Pr Tags: Clin Cancer Res Source Type: research

Arylsulfonamide 64B inhibits hypoxia/HIF-induced expression of c-Met and CXCR4 and reduces primary tumor growth and metastasis of uveal melanoma.
Abstract PURPOSE: Uveal melanoma (UM) is the most prevalent and lethal intraocularmalignancy in adults. Here, we examined the importance of hypoxia in UM growth and tested the anti-tumor effects of arylsulfonamide 64B, an inhibitor of the hypoxia-induced factor (HIF) pathway in animal models of UM and investigated the related mechanisms. EXPERIMENTAL DESIGN: UM cells were implanted in the uvea of mice eyes and mice systemically treated with 64B. Drug effect on primary eye tumor growth, circulating tumor cells, metastasis formation in liver and survival were examined. 64B effects on UM cell growth, invasion an...
Source: Clinical Cancer Research - December 18, 2018 Category: Cancer & Oncology Authors: Van Meir EG, Dong L, You S, Zhang Q, Osuka S, Devi NS, Kaluz S, Holmes JN, Yang H, Chen G, Wang B, Grossniklaus HE Tags: Clin Cancer Res Source Type: research

Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers.
Conclusions: Binimetinib with gemcitabine and cisplatin did not show an improvement in PFS 6 and RR. Molecular profiling may help select patients who may benefit from this triplet therapy, which is not planned at this time. PMID: 30563938 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 18, 2018 Category: Cancer & Oncology Authors: Lowery MA, Bradley M, Chou JF, Capanu M, Gerst S, Harding JJ, Dika IE, Berger M, Zehir A, Ptashkin R, Wong P, Rasalan-Ho T, Yu KH, Cercek A, Morgono E, Salehi E, Valentino E, Hollywood E, O'Reilly EM, Abou-Alfa GK Tags: Clin Cancer Res Source Type: research

Human breast cancer xenograft model implicates peroxisome proliferator-activated receptor signaling as driver of cancer-induced muscle fatigue.
CONCLUSIONS: Collectively, these data demonstrate that the BC-PDOX model recapitulates the expected BC-induced SkM fatigue and further identify aberrant PPAR signaling as an integral factor in the pathology of this condition. PMID: 30559167 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 17, 2018 Category: Cancer & Oncology Authors: Wilson HE, Rhodes KK, Rodriguez D, Chahal I, Stanton DA, Bohlen J, Davis M, Infante AM, Hazard-Jenkins H, Klinke DJ, Pugacheva EN, Pistilli EE Tags: Clin Cancer Res Source Type: research