Changes in diffuse-optical-tomography images during early stages of neoadjuvant chemotherapy correlate with tumor response in different breast cancer subtypes.
This study's primary objective is to evaluate the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the tumor volume of patients with breast carcinoma receiving neoadjuvant chemotherapy (NAC). EXPERIMENTAL DESIGN: In this analysis of 105 patients with stage II-III breast cancer, normalized mean values of total hemoglobin (ctTHbN), oxyhemoglobin (ctO2HbN), deoxy-hemoglobin concentration (ctHHbN), water and oxygen saturation (StO2N) percentages were collected at different time points during NAC and compared with baseline measurements. This report compared...
Source: Clinical Cancer Research - January 15, 2021 Category: Cancer & Oncology Authors: Altoe M, Kalinsky K, Marone A, Kim HK, Guo H, Hibshoosh H, Tejada M, Crew KD, Accordino M, Trivedi MS, Hershman DL, Hielscher AH Tags: Clin Cancer Res Source Type: research

Phase 1 Study of the CD47 Blocker TTI-621 in Patients with Relapsed or Refractory Hematologic Malignancies.
CONCLUSIONS: TTI-621 was well tolerated and demonstrated activity as monotherapy in patients with R/R B-NHL and T-NHL and combined with rituximab in patients with R/R B-NHL. PMID: 33451977 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 15, 2021 Category: Cancer & Oncology Authors: Ansell SM, Maris M, Lesokhin AM, Chen R, Flinn IW, Sawas A, Minden MD, Villa D, Percival MM, Advani AS, Foran JM, Horwitz S, Mei M, Zain J, Savage KJ, Querfeld C, Akilov OE, Johnson LD, Catalano T, Petrova PS, Uger RA, Sievers EL, Milea A, Roberge K, Shou Tags: Clin Cancer Res Source Type: research

Randomized phase II trial of sipuleucel-T with or without radium-223 in men with bone-metastatic castration-resistant prostate cancer.
CONCLUSION: Our data raise the possibility of greater clinical activity with the combination of sipuleucel-T and radium-223 in men with asymptomatic bone mCRPC, despite the paradoxically lower immune responses observed. Additional study to confirm these findings in a larger trial is warranted. PMID: 33451978 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 15, 2021 Category: Cancer & Oncology Authors: Marshall CH, Fu W, Wang H, Park JC, DeWeese TL, Tran PT, Song DY, King S, Afful M, Hurrelbrink J, Manogue CE, Cotogno P, Moldawer NP, Barata P, Drake CG, Posadas EM, Armstrong AJ, Sartor O, Antonarakis ES Tags: Clin Cancer Res Source Type: research

HAND1 and BARX1 act as transcriptional and anatomic determinants of malignancy in gastrointestinal stromal tumor.
Conclusions: Our results define anatomic and transcriptional determinants of GIST and molecular origins of clinical phenotypes. Assessment of HAND1 and BARX1 expression in GIST may provide prognostic information and improve clinical decisions on the administration of adjuvant therapy. PMID: 33451979 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 15, 2021 Category: Cancer & Oncology Authors: Hemming ML, Coy S, Lin JR, Andersen JL, Przybyl J, Mazzola E, Abdelhamid Ahmed AH, van de Rijn M, Sorger PK, Armstrong SA, Demetri GD, Santagata S Tags: Clin Cancer Res Source Type: research

A MET Targeting Antibody-Drug Conjugate Overcomes Gemcitabine Resistance in Pancreatic Cancer.
CONCLUSIONS: Together these results suggest the promise of agents such as TR1801-ADC as a novel approach to the treatment of pancreatic cancer. PMID: 33451980 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 15, 2021 Category: Cancer & Oncology Authors: Cazes A, Betancourt O, Esparza E, Mose ES, Jaquish D, Wong E, Wascher AA, Tiriac H, Gymnopoulos M, Lowy AM Tags: Clin Cancer Res Source Type: research

A bispecific single domain antibody boosts autologous V γ9Vδ2-T cell responses towards CD1d in chronic lymphocytic leukemia.
CONCLUSION: Collectively, our data demonstrate the immunotherapeutic potential of this novel CD1d-specific Vγ9Vδ2-T cell engager in CLL. PMID: 33451981 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 15, 2021 Category: Cancer & Oncology Authors: de Weerdt I, Lameris R, Ruben JM, de Boer R, Kloosterman J, King LA, Levin MD, Parren PWHI, de Gruijl TD, Kater AP, van der Vliet HJ Tags: Clin Cancer Res Source Type: research

The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers.
Abstract PURPOSE: Using RNA sequencing, we recently developed the 52-gene-based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. EXPERIMENTAL DESIGN: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and che...
Source: Clinical Cancer Research - January 14, 2021 Category: Cancer & Oncology Authors: Hu Z, Cunnea P, Zhong Z, Lu H, Osagie OI, Campo L, Artibani M, Nixon K, Ploski J, Santana Gonzalez L, Alsaadi A, Wietek N, Damato S, Dhar S, Blagden SP, Yau C, Hester J, Albukhari A, Aboagye EO, Fotopoulou C, Ahmed A Tags: Clin Cancer Res Source Type: research

Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score {greater than or equal to}10.
CONCLUSIONS: This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS{greater than or equal to}10 G/GEJ cancer. PMID: 33446564 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 14, 2021 Category: Cancer & Oncology Authors: Wainberg ZA, Fuchs CS, Tabernero J, Shitara K, Muro K, Van Cutsem E, Bang YJ, Chung HC, Yamaguchi K, Varga E, Chen JS, Hochhauser D, Thuss-Patience PC, Al-Batran SE, Garrido M, Kher U, Shih CS, Shah S, Bhagia P, Chao J Tags: Clin Cancer Res Source Type: research

Diffusion-weighted imaging allows for downgrading MR BI-RADS 4 lesions in contrast-enhanced MRI of the breast to avoid unnecessary biopsy.
CONCLUSIONS: An ADC cut-off of {greater than or equal to}1.5*10-3 mm2/s allows downgrading of lesions classified as BI-RADS 4 on breast CE-MRI. One-third of unnecessary biopsies could thus be avoided. PMID: 33446565 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 14, 2021 Category: Cancer & Oncology Authors: Clauser P, Krug B, Bickel H, Dietzel M, Pinker-Domenig K, Neuhaus VF, Marino MA, Moschetta M, Troiano N, Helbich TH, Baltzer PA Tags: Clin Cancer Res Source Type: research

Clinical Proteomics of Metastatic Melanoma Reveals Profiles of Organ-Specificity and Treatment Resistance.
CONCLUSIONS: Altogether, the proteomic data provided novel molecular determinants of critical clinical features, including the effects of sequential treatments and metastatic locations. These results can be the basis for development of site-specific treatments toward treatment personalization. PMID: 33446566 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 14, 2021 Category: Cancer & Oncology Authors: Geiger T, Beck L, Harel M, Yu S, Markovits E, Boursi B, Markel G Tags: Clin Cancer Res Source Type: research

Whole Exome Sequencing in Penile Squamous Cell Carcinoma Uncovers Novel Prognostic Categorization and Drug Targets Similar to Head and Neck Squamous Cell Carcinoma.
We report the first whole exome sequencing analysis and compare the molecular landscape of PSCC to other SCCs, with the goal to identify common novel targets. PATIENTS AND METHODS: PSCC and matched normal penile tissues from 34 prospectively followed patients, underwent genomic whole exome sequencing and human papilloma virus testing. We performed tumor mutation signature estimation by two methods, first to identify APOBEC-related mutation enrichments and second to classify PSCC enriched mutational patterns based on their association with the COSMIC mutation signatures. We performed an extensive genomic comparison bet...
Source: Clinical Cancer Research - January 13, 2021 Category: Cancer & Oncology Authors: Chahoud J, Gleber-Netto FO, McCormick BZ, Rao P, Lu X, Guo M, Morgan MB, Chu RA, Martinez-Ferrer M, Eterovic AK, Pickering CR, Pettaway CA Tags: Clin Cancer Res Source Type: research

Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors.
CONCLUSIONS: This TIM-3 and PD-L1 bispecific format was associated with unexpected immunogenicity targeting both arms of the bispecific antibody, resulting in early study termination. Epitope specificity analysis revealed an initial response towards the TIM-3 arm and presence of pre‑existing ADAs to the bispecific molecule in the general population. This experience emphasizes the importance of thorough analyses for pre‑existing ADAs as part of immunogenicity risk assessment of novel antibodies. PMID: 33441294 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 13, 2021 Category: Cancer & Oncology Authors: Hellmann MD, Bivi N, Calderon B, Shimizu T, Delafontaine B, Liu ZT, Szpurka AM, Copeland V, Hodi FS, Rottey S, Aftimos P, Piao Y, Gandhi L, Galvao VR, Leow CC, Doi T Tags: Clin Cancer Res Source Type: research

PSA-targeted Alpha-, Beta- and Positron Emitting Immuno-Theranostics in Murine Prostate Cancer Models and Non-Human Primates.
t D Abstract PURPOSE: Most prostate cancer (PCa) patients treated with androgen receptor (AR)-signaling inhibitors develop therapeutic resistance due to restoration of AR-functionality. Thus, there is a critical need for novel treatment approaches. Here we investigate the theranostic potential of hu5A10, a humanized monoclonal antibody specifically targeting free prostate-specific antigen (KLK3). EXPERIMENTAL DESIGN: LNCaP-AR xenografts (NSG mice) and KLK3_Hi-Myc transgenic mice were imaged with 89Zr- or treated with 90Y- or 225Ac-labeled hu5A10; biodistribution and subcellular localization were analyzed by g...
Source: Clinical Cancer Research - January 13, 2021 Category: Cancer & Oncology Authors: Veach D, Storey CM, Lueckerath K, Braun K, von Bodman C, Lamminmäki U, Kalidindi TM, Strand SE, Strand J, Altai M, Damoiseaux R, Zanzonico PB, Benabdallah N, Pankov D, Scher HI, Scardino P, Larson SM, Lilja HG, McDevitt MR, Thorek DL, Ulmert D Tags: Clin Cancer Res Source Type: research

Follicular lymphoma-associated BTK mutations are inactivating resulting in augmented AKT activation.
CONCLUSIONS: Altogether, our data uncover novel unexpected properties of FL-associated BTK mutations with direct implications for targeted therapy development in FL. PMID: 33419778 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 8, 2021 Category: Cancer & Oncology Authors: Malek S, Hu N, Wang F, Sun T, Xu Z, Zhang J, Bernard D, Xu S, Wang S, Kaminski MS, Devata S, Phillips T Tags: Clin Cancer Res Source Type: research

Targeting oxidative phosphorylation to increase the efficacy of radio- and immune- combination therapy.
Abstract As tumors grow, they upregulate glycolytic and oxidative metabolism to support their increased and altered energetic demands. These metabolic changes have major effects on the tumor microenvironment (TME). One of the properties leading to this aberrant metabolism is hypoxia, which occurs when tumors outgrow their, often chaotic, vasculature. This scarcity of oxygen is known to induce radioresistance, but can also have a disrupting effect on the anti-tumor immune response. Hypoxia inhibits immune effector cell function, while immune cells with a more suppressing phenotype become more active. Therefore, hyp...
Source: Clinical Cancer Research - January 8, 2021 Category: Cancer & Oncology Authors: Boreel DF, Span PN, Heskamp S, Adema GJ, Bussink J Tags: Clin Cancer Res Source Type: research

Network for biomarker immunoprofiling for cancer immunotherapy: Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC).
piridion B, Ranasinghe S, Pichavant M, Del Valle DM, Yu J, Janssens S, Peterson-Klaus J, Rowe C, Bongers G, Jenq RR, Chang CC, Abrams JS, Mooney M, Doroshow JH, Harris LN, Thurin M Abstract Immunoprofiling to identify biomarkers and integration with clinical trials outcome are critical to improve immunotherapy approaches for cancer patients. However, the translational potential of individual studies is often limited by small sample size of trials and the complexity of immuno-oncology biomarkers. Variability in assays further limits comparison and interpretation of data across studies and laboratories. To enable a ...
Source: Clinical Cancer Research - January 8, 2021 Category: Cancer & Oncology Authors: Chen HX, Song M, Maecker HT, Gnjatic S, Patton D, Lee JJ, Adam SJ, Moravec R, Liu XS, Cerami E, Lindsay J, Hodi FS, Wu C, Wistuba II, Al-Atrash G, Bernatchez C, Bendall SC, Hewitt SM, Sharon E, Streicher H, Enos RA, Bowman MD, Tatard-Leitman VM, Sanchez-E Tags: Clin Cancer Res Source Type: research

Interventional radiology for local immunotherapy in oncology.
Abstract Human intratumoral immunotherapy (HIT-IT) is under rapid development with promising preliminary results and high expectations for current phase 3 trials. While outcomes remain paramount for patients and the referring oncologists, the technical aspects of drug injection are critical to the interventional radiologist in order to ensure optimal and reproducible outcomes. The technical considerations for HIT-IT impact the safety, efficacy and further development of this treatment option. Image-guided access to the tumor allows to enhance the therapeutic index of a treatment by increasing the intra-tumoral dru...
Source: Clinical Cancer Research - January 8, 2021 Category: Cancer & Oncology Authors: Tselikas L, Champiat S, Sheth RA, Yevich S, Ammari S, Deschamps F, Farhane S, Roux C, Susini S, Mouraud S, Delpla A, Raoult T, Robert C, Massard C, Barlesi F, Soria JC, Marabelle A, De Baere T Tags: Clin Cancer Res Source Type: research

The State of Melanoma: Emergent Challenges and Opportunities.
In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome and offer recommendations for the best path forward. PMID: 33414132 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2021 Category: Cancer & Oncology Authors: Atkins MB, Curiel-Lewandrowski C, Fisher DE, Swetter SM, Tsao H, Aguirre-Ghiso JA, Soengas MS, Weeraratna AT, Flaherty KT, Herlyn M, Sosman JA, Tawbi HA, Pavlick AC, Cassidy PB, Chandra S, Chapman PB, Daud A, Eroglu Z, Ferris LK, Fox BA, Gerhsenwald JE, G Tags: Clin Cancer Res Source Type: research

ARID1A mutation may define an immunologically active subgroup in patients with microsatellite-stable colorectal cancer.
Abstract PURPOSE: ARID1A is commonly mutated in colorectal cancer (CRC), frequently resulting in truncation and loss of protein expression. ARID1A recruits MSH2 for mismatch-repair during DNA replication. ARID1A deficiency promotes hypermutability and immune activation in preclinical models but its role in CRC patients is being explored. EXPERIMENTAL DESIGN: The DNA sequencing and gene expression profiling of CRC patients were extracted from TCGA and MDACC databases, with validation utilizing external databases, and correlation between ARID1A and immunologic features. Immunohistochemistry for T-cell markers w...
Source: Clinical Cancer Research - January 7, 2021 Category: Cancer & Oncology Authors: Mehrvarz Sarshekeh A, Alshenaifi J, Roszik J, Manyam G, Advani SM, Katkhuda R, Verma A, Lam M, Willis JA, Shen JP, Morris JS, Davis JS, Loree JM, Lee HM, Ajani JA, Maru DM, Overman MJ, Kopetz S Tags: Clin Cancer Res Source Type: research

Double-hit signature with TP53 abnormalities predicts poor survival in patients with germinal center type diffuse large B-cell lymphoma treated with R-CHOP.
CONCLUSIONS: We propose a practical schema to utilize genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies. PMID: 33414134 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2021 Category: Cancer & Oncology Authors: Song JY, Perry AM, Herrera AF, Chen L, Skrabek P, Nasr M, Ottesen R, Nikowitz J, Bedell V, Murata-Collins JL, Li Y, McCarthy C, Pillai RK, Wang J, Wu X, Popplewell L, Kwak LW, Nademanee A, Niland JC, Scott DW, Gong Q, Chan WC, Weisenburger D Tags: Clin Cancer Res Source Type: research

BRCA2, ATM, and CDK12 defects differentially shape prostate tumor driver genomics and clinical aggression.
CONCLUSIONS: BRCA2, ATM, and CDK12 defects are each linked to distinct prostate cancer driver genomics and aggression. The consistency of DDR status in longitudinal samples and resolution of allelic status underscores the potential for ctDNA as a diagnostic tool. PMID: 33414135 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2021 Category: Cancer & Oncology Authors: Warner EW, Herberts C, Fu S, Yip SM, Wong A, Wang G, Ritch E, Murtha AJ, Vandekerkhove G, Fonseca N, Angeles A, Beigi A, Schönlau E, Beja K, Annala M, Khalaf DJ, Chi KN, Wyatt AW Tags: Clin Cancer Res Source Type: research

Molecular Characterization and Therapeutic Targeting of Colorectal Cancers Harboring Receptor Tyrosine Kinase Fusions.
CONCLUSIONS: RTK fusions in CRC are a rare but important disease subgroup that occur in RAS and BRAF wild-type tumors. Despite enrichment in acquired MMR-D tumors, RTK fusions also occur in microsatellite-stable CRC and provide an important therapeutic target. PMID: 33414136 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2021 Category: Cancer & Oncology Authors: Singh H, Li YY, Spurr LF, Shinagare AB, Abhyankar R, Reilly E, Brais LK, Nag A, Ducar MD, Thorner AR, Shapiro GI, Keller RB, Siletti C, Clark JW, Farago AF, Lin JJ, Demetri GD, Gujrathi R, Kulke MH, MacConaill LE, Ligon AH, Sicinska E, Meyerson M, Meyerha Tags: Clin Cancer Res Source Type: research

Combining neratinib with CDK4/6, mTOR and MEK inhibitors in models of HER2-positive cancer.
CONCLUSION: Taken together, our results provide strong preclinical evidence for combining neratinib with CDK4/6, mTOR and MEK inhibitors for the treatment of HER2+ cancer. PMID: 33414137 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2021 Category: Cancer & Oncology Authors: Zhao M, Scott S, Evans KW, Yuca E, Saridogan T, Zheng X, Wang H, Korkut A, Cruz Pico CX, Demirhan ME, Kirby B, Kopetz S, Diala I, Lalani AS, Piha-Paul S, Meric-Bernstam F Tags: Clin Cancer Res Source Type: research

Integrated Molecular Characterization of Fumarate Hydratase-deficient Renal Cell Carcinoma.
CONCLUSIONS: These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC. PMID: 33414138 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 7, 2021 Category: Cancer & Oncology Authors: Sun G, Zhang X, Liang J, Pan X, Zhu S, Liu Z, Armstrong CM, Chen J, Lin W, Liao B, Lin T, Huang R, Zhang M, Zheng L, Yin X, Nie L, Shen PF, Zhao J, Zhang H, Dai J, Shen Y, Li Z, Liu JY, Chen J, Liu J, Wang Z, Zhu X, Ni Y, Qin D, Yang L, Chen Y, Wei Q, Li Tags: Clin Cancer Res Source Type: research

PET imaging of TIGIT expression on tumor-infiltrating lymphocytes.
CONCLUSIONS: This study develops and validates novel TIGIT-specific 64Cu and 89Zr PET probes for quantifying TIGIT expression on TILs for diagnosis of patient selection for anti-TIGIT therapies. PMID: 33408249 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 6, 2021 Category: Cancer & Oncology Authors: Shaffer T, Natarajan A, Gambhir SS Tags: Clin Cancer Res Source Type: research

Inflammation mediates the development of aggressive breast cancer following radiotherapy.
CONCLUSIONS: These data show that radiation acts via non-mutational mechanisms to promote markedly immunosuppressive features of aggressive, radiation-preceded breast cancers. PMID: 33402361 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 5, 2021 Category: Cancer & Oncology Authors: Ma L, Gonzalez-Junca A, Zheng Y, Ouyang H, Illa-Bochaca I, Horst KC, Krings G, Wang Y, Fernandez-Garcia I, Chou W, Barcellos-Hoff MH Tags: Clin Cancer Res Source Type: research

Selected Articles from This Issue.
Authors: PMID: 33397678 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 1, 2021 Category: Cancer & Oncology Tags: Clin Cancer Res Source Type: research

Drug-Radiotherapy Combination Trial Developments-Letter.
PMID: 33397679 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 1, 2021 Category: Cancer & Oncology Authors: Evans JR, Cuneo KC, Lawrence TS Tags: Clin Cancer Res Source Type: research

Drug-Radiotherapy Combination Trial Developments-Response.
PMID: 33397680 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 1, 2021 Category: Cancer & Oncology Authors: Deutsch E, Chargari C, Weichselbaum RR, Levy A Tags: Clin Cancer Res Source Type: research

Correction: Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-unrelated Head and Neck Cancer: A Multicenter, Phase II Trial.
, Jo VY, Stachler MD, Hanna GJ, Kass J, Haddad R, Schoenfeld JD, Gjini E, Lako A, Thorstad W, Gay HA, Daly M, Rodig SJ, Hagemann IS, Kallogjeri D, Piccirillo JF, Chernock RD, Griffith M, Griffith OL, Adkins DR PMID: 33397681 [PubMed] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 1, 2021 Category: Cancer & Oncology Authors: Uppaluri R, Campbell KM, Egloff AM, Zolkind P, Skidmore ZL, Nussenbaum B, Paniello RC, Rich JT, Jackson R, Pipkorn P, Michel LS, Ley J, Oppelt P, Dunn GP, Barnell EK, Spies NC, Lin T, Li T, Mulder DT, Hanna Y, Cirlan I, Pugh TJ, Mudianto T, Riley R, Zhou Tags: Clin Cancer Res Source Type: research

Correction: Immune Checkpoint Blockade in Combination with Stereotactic Body Radiotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma.
PMID: 33397682 [PubMed] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 1, 2021 Category: Cancer & Oncology Authors: Xie C, Duffy AG, Brar G, Fioravanti S, Mabry-Hrones D, Walker M, Bonilla CM, Wood BJ, Citrin DE, Gil Ramirez EM, Escorcia FE, Redd B, Hernandez JM, Davis JL, Gasmi B, Kleiner D, Steinberg SM, Jones JC, Greten TF Tags: Clin Cancer Res Source Type: research

A Blood-based Assay for Assessment of Tumor Mutational Burden in First-line Metastatic NSCLC Treatment: Results from the MYSTIC Study.
CONCLUSIONS: Our study demonstrates the feasibility, accuracy, and reproducibility of the GuardantOMNI ctDNA platform for quantifying bTMB from plasma samples. Using the new bTMB algorithm and an optimal bTMB cut-off of ≥20 mut/MB, high bTMB was predictive of clinical benefit with durvalumab + tremelimumab versus chemotherapy. PMID: 33355200 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 22, 2020 Category: Cancer & Oncology Authors: Si H, Kuziora M, Quinn KJ, Helman E, Ye J, Liu F, Scheuring U, Peters S, Rizvi NA, Brohawn P, Ranade K, Higgs BW, Banks KC, Chand VK, Raja R Tags: Clin Cancer Res Source Type: research

LXH254, a potent and selective ARAF-sparing inhibitor of BRAF and CRAF for the treatment of MAPK-driven tumors.
CONCLUSIONS: LXH254 is a novel RAF-inhibitor able to inhibit dimerized BRAF and CRAF as well as monomeric BRAF while largely sparing ARAF. PMID: 33355204 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 22, 2020 Category: Cancer & Oncology Authors: Monaco KA, Delach S, Yuan J, Mishina Y, Fordjour P, Labrot E, McKay D, Guo R, Higgins S, Wang HQ, Liang J, Bui K, Green J, Aspesi P, Ambrose J, Mapa F, Griner L, Jaskelioff M, Fuller J, Crawford K, Pardee G, Widger S, Hammerman PS, Engelman JA, Stuart DD, Tags: Clin Cancer Res Source Type: research

VLA4-nanoparticles hijack cell adhesion mediated drug resistance (CAM-DR) to target refractory myeloma cells and prolong survival.
CONCLUSIONS: V-CP may be a safe and effective strategy to prevent or treat relapsing or refractory myeloma. V-NP targeting of resistant cells may suggest a new approach to environment-induced resistance in cancer. CONCLUSIONS: V-CP may be a safe and effective strategy to prevent or treat relapsing or refractory myeloma. V-NP targeting of resistant cells may suggest a new approach to environment-induced resistance in cancer. PMID: 33355244 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 22, 2020 Category: Cancer & Oncology Authors: Fontana F, Scott MJ, Allen JS, Yang X, Cui G, Pan D, Yanaba N, Fiala MA, O'Neal J, Schmieder-Atteberry AH, Ritchey J, Rettig M, Simons K, Fletcher S, Vij R, DiPersio J, Lanza G Tags: Clin Cancer Res Source Type: research

177Lu-DOTA-EB-TATE, A Radiolabeled Analog of Somatostatin Receptor Type 2, for the Imaging and Treatment of Thyroid Cancer.
Abstract PURPOSE: The goal of this study was to analyze the role of somatostatin receptor type 2 (SSTR2) as a molecular target for the imaging and treatment of thyroid cancer (TC) through analysis of SSTR2 expression and its epigenetic modulation and testing tumor uptake of different radiolabeled SSTR2 analogs. EXPERIMENTAL DESIGN: We analyzed SSTR2 expression by immunostaining of 92 TC tissue samples and quantified standard uptake values (SUVmax) of SSTR2 analog 68Ga-DOTATATE by positron emission/computed tomography (PET/CT) imaging in 25 patients with metastatic TC. We utilized human TC cell lines character...
Source: Clinical Cancer Research - December 22, 2020 Category: Cancer & Oncology Authors: Thakur S, Daley B, Millo C, Cochran C, Jacobson O, Lu H, Wang Z, Kiesewetter DO, Chen X, Vasko VV, Klubo-Gwiezdzinska J Tags: Clin Cancer Res Source Type: research

Genome methylation accurately predicts neuroendocrine tumor origin - an online tool.
CONCLUSIONS: This DNA methylation-based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID. PMID: 33355250 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 22, 2020 Category: Cancer & Oncology Authors: Hackeng WM, Dreijerink KMA, de Leng WWJ, Morsink FH, Valk GD, Vriens MR, Offerhaus GJA, Geisenberger C, Brosens LAA Tags: Clin Cancer Res Source Type: research

Tarloxotinib is a hypoxia-activated pan-HER kinase inhibitor active against a broad range of HER-family oncogenes.
CONCLUSIONS: Experimental data with tarloxotinib validate the novel mechanism of action of a hypoxia-activated prodrug in cancer models by concentrating active drug in the tumor vs. normal tissue and this activity can translate into clinical activity in patients. PMID: 33355298 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 22, 2020 Category: Cancer & Oncology Authors: Estrada-Bernal A, Le AT, Doak AE, Tirunagaru VG, Silva S, Bull MR, Smaill JB, Patterson AV, Kim C, Liu SV, Doebele RC Tags: Clin Cancer Res Source Type: research

MEK-ing the most of it: strategies to co-target G αq and MAPK in uveal melanoma.
MEK-ing the most of it: strategies to co-target Gαq and MAPK in uveal melanoma. Clin Cancer Res. 2020 Dec 22;: Authors: Neelature Sriramareddy S, Smalley KSM Abstract Most uveal melanomas harbor mutations in Gαq and show constitutive MAPK activation. Although MEK inhibition has some efficacy against uveal melanoma, clinical responses are typically poor. The Gαq inhibitor-MEK inhibitor combination showed prolonged suppression of MAPK signaling in preclinical uveal melanoma models and led to improved therapeutic responses. PMID: 33355300 [PubMed - as supplied by publisher] (Source...
Source: Clinical Cancer Research - December 22, 2020 Category: Cancer & Oncology Authors: Neelature Sriramareddy S, Smalley KSM Tags: Clin Cancer Res Source Type: research

Phase I Study of MK-4166, an Anti-Human Glucocorticoid-Induced Tumor Necrosis Factor Receptor Antibody, Alone or With Pembrolizumab in Advanced Solid Tumors.
CONCLUSIONS: MK-4166 900 mg IV Q3W as monotherapy and with pembrolizumab was tolerable. Responses were observed with combination therapy, mostly in patients with ICI-naive melanoma. PMID: 33355238 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 21, 2020 Category: Cancer & Oncology Authors: Papadopoulos KP, Autio KA, Golan T, Dobrenkov K, Chartash E, Chen Q, Wnek R, Long GV Tags: Clin Cancer Res Source Type: research

Early discontinuation of endocrine therapy and recurrence of breast cancer among premenopausal women.
CONCLUSION: These results highlight the importance of clinical follow-up and behavioral interventions that support persistence of adjuvant endocrine therapy to prevent breast cancer recurrence. PMID: 33334905 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 17, 2020 Category: Cancer & Oncology Authors: Collin LJ, Cronin-Fenton D, Ahern TP, Goodman M, McCullough LE, Waller LA, Kjærsgaard A, Damkier P, Christiansen PM, Ejlertsen B, Jensen MB, Sorensen HT, Lash TL Tags: Clin Cancer Res Source Type: research

Attenuation of SRC kinase activity augments PARP inhibitor-mediated synthetic lethality in BRCA2-altered prostate tumors.
CONCLUSIONS: This work suggests that SRC activation may be a potential mechanism of PARPi resistance and that treatment with SRC inhibitors may overcome this resistance. Our preclinical study demonstrates that combining PARPi and SRC inhibitors may be a promising therapeutic strategy for patients with BRCA2-null mCRPC. PMID: 33334906 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 17, 2020 Category: Cancer & Oncology Authors: Chakraborty G, Khan Patail N, Hirani R, Nandakumar S, Mazzu YZ, Yoshikawa Y, Atiq MO, Jehane L, Stopsack KH, Lee GM, Abida W, Morris MJ, Mucci LA, Danila DC, Kantoff PW Tags: Clin Cancer Res Source Type: research

Osimertinib Plus Ramucirumab: The Best of Both Worlds?
Abstract Both osimertinib and the combination of erlotinib plus ramuciumab are approved for initial therapy of advanced epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC). Osimertinib is also approved in previously treated T790M mutation positive patients. The accompanying manuscript reports on a study combining osimertinib with ramucirumab. PMID: 33334907 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 17, 2020 Category: Cancer & Oncology Authors: Garon EB Tags: Clin Cancer Res Source Type: research

Combined PD-1/VEGFR blockade: a new era of treatment for hepatocellular cancer.
Abstract Combination immunotherapy is an expanding therapeutic modality in hepatocellular carcinoma (HCC), a disease where single-agent immunotherapy has failed to lead to survival benefit. The RESCUE trial adds camrelizumab and apatinib to the therapeutic armamentarium of advanced HCC, raising questions around the optimal positioning of various combination regimens in liver cancer. PMID: 33328343 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 16, 2020 Category: Cancer & Oncology Authors: Pinato DJ, Fessas P, Cortellini A, Rimassa L Tags: Clin Cancer Res Source Type: research

Transcription strikes back: clinical utility of lung adenocarcinoma subtypes.
Abstract Using transcriptional profiling, three robust subtypes of non-squamous NSCLC are defined, independently of initiating oncogenic driver events. Subtype-specific differential sensitivity to MEK1/2 inhibitors is reported and an interaction between the mucinous subtype, STK11/LKB1 genomic alterations and inferior clinical outcomes with atezolizumab in the OAK clinical trial is identified. PMID: 33328344 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 16, 2020 Category: Cancer & Oncology Authors: Skoulidis F Tags: Clin Cancer Res Source Type: research

Predicting CAR-T cell immunotherapy success through immunoPET.
Abstract Chimeric antigen receptor (CAR) T cell therapy has generated unprecedent advances in the treatment of hematologic cancers, but readily translatable imaging approaches to visualize the in vivo dynamics of CAR-T cells are lacking. Non-invasive positron emission tomography (PET) imaging is the ideal tool to monitor CAR-T cells. PMID: 33328345 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 16, 2020 Category: Cancer & Oncology Authors: Volpe A, Nagle VL, Lewis JS, Ponomarev V Tags: Clin Cancer Res Source Type: research

Selected Articles from This Issue.
Authors: PMID: 33323361 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2020 Category: Cancer & Oncology Tags: Clin Cancer Res Source Type: research

Correction: The First-week Proliferative Response of Peripheral Blood PD-1+CD8+ T Cells Predicts the Response to Anti-PD-1 Therapy in Solid Tumors.
PMID: 33323362 [PubMed] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2020 Category: Cancer & Oncology Authors: Kim KH, Cho J, Ku BM, Koh J, Sun JM, Lee SH, Ahn JS, Cheon J, Min YJ, Park SH, Park K, Ahn MJ, Shin EC Tags: Clin Cancer Res Source Type: research

The genetic evolution of treatment-resistant cutaneous, acral and uveal melanomas.
CONCLUSIONS: In four patients who received immunotherapy, we found 1-3 putative acquired and intrinsic resistance mechanisms coexisting in the same patient, including mechanisms that were shared by all tumors within each patient, suggesting that future therapies directed at overcoming intrinsic resistance mechanisms may be broadly effective. PMID: 33323400 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2020 Category: Cancer & Oncology Authors: Makohon-Moore AP, Lipson EJ, Hooper JE, Zucker A, Hong J, Bielski CM, Hayashi A, Tokheim C, Baez P, Kappagantula R, Kohutek Z, Makarov V, Riaz N, Postow MA, Chapman PB, Karchin R, Socci ND, Solit DB, Chan TA, Taylor BS, Topalian SL, Iacobuzio-Donahue CA Tags: Clin Cancer Res Source Type: research

Efficacy and biomarker analysis of camrelizumab in combination with apatinib in patients with advanced non-squamous NSCLC previously treated with chemotherapy.
CONCLUSIONS: Combined apatinib and camrelizumab showed encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced non-squamous NSCLC. Patients with STK11/KEAP1 mutation might derive more benefits from this combination. We will validate these results in an ongoing phase III trial (NCT04203485). PMID: 33323401 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2020 Category: Cancer & Oncology Authors: Zhou C, Wang Y, Zhao J, Chen G, Liu Z, Gu K, Huang M, He J, Chen J, Ma Z, Feng J, Shi J, Yu X, Cheng Y, Yao Y, Chen Y, Guo R, Lin X, Wang ZH, Gao G, Wang QR, Li W, Yang X, Wu L, Zhang J, Ren S Tags: Clin Cancer Res Source Type: research

Cross-site concordance evaluation of tumor DNA and RNA sequencing platforms for the CIMAC-CIDC network.
CONCLUSIONS: The CIMAC collaborating laboratory platforms effectively generated consistent WES and RNA-seq data and enable robust cross-trial comparisons and meta-analyses of highly complex immuno-oncology biomarker data across the NCI CIMAC-CIDC Network. PMID: 33323402 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - December 15, 2020 Category: Cancer & Oncology Authors: Zeng Z, Fu J, Cibulskis C, Jhaveri A, Gumbs C, Das B, Sanchez-Espiridion B, Janssens S, Taing L, Wang J, Lindsay J, Vilimas T, Zhang J, Tokheim C, Das Sahu A, Jiang P, Yan C, Duose DY, Cerami E, Chen L, Cohen D, Chen QR, Enos RA, Huang X, Lee JJ, Liu Y, N Tags: Clin Cancer Res Source Type: research