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Multiomic mapping of acquired chromosome 1 copy number and structural variants to identify therapeutic vulnerabilities in multiple myeloma. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-14 Eileen M Boyle,Patrick Blaney,James H Stoeckle,Yubao Wang,Hussein Ghamlouch,Dylan Gagler,Marc Braunstein,Louis Williams,Avital Tenenbaum,Ariel Siegel,Xiaoyi Chen,Gaurav Varma,Jason Avigan,Alexander Li,Monica Jinsi,David Kaminetzky,Arnaldo Arbini,Lydia Montes,Jill Corre,Even H Rustad,Ola Landgren,Francesco Maura,Brian A Walker,Michael Bauer,Benedetto Bruno,Aristotelis Tsirigos,Faith E Davies,Gareth
PURPOSE Chromosome 1 (chr1) copy number abnormalities (CNAs) and structural variants (SV) are frequent in newly diagnosed multiple myeloma (NDMM) and associate with a heterogeneous impact on outcome the drivers of which are largely unknown. EXPERIMENTAL DESIGN A multiomic approach comprising CRISPR, gene mapping of CNA and SV, methylation, expression, and mutational analysis was used to document the
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HLA-I evolutionary divergence confers response to PD-1 blockade plus chemotherapy in untreated advanced non-small-cell lung cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-14 Tao Jiang,Qiqi Jin,Jiahao Wang,Fengying Wu,Jian Chen,Gongyan Chen,Yunchao Huang,Jianhua Chen,Ying Cheng,QiMing Wang,Yueyin Pan,Jianying Zhou,Jianhua Shi,Xingxiang Xu,LiZhu Lin,Wei Zhang,Yiping Zhang,Yunpeng Liu,Yong Fang,Jifeng Feng,Zhehai Wang,Sheng Hu,Jian Fang,Yongqian Shu,Jiuwei Cui,Yi Hu,Wenxiu Yao,Xingya Li,Xiaoyan Lin,Rui Wang,Yongsheng Wang,Wei Shi,Gaohua Feng,Jun Ni,Beibei Mao,Dandan Ren,Huaibo
PURPOSE PD-1 blockade plus chemotherapy has become the new standard of care in patients with untreated advanced non-small-cell lung cancer (NSCLC), whereas predictive biomarkers remain undetermined. PATIENTS AND METHODS We integrated clinical, genomic and survival data of 427 NSCLC patients treated with first-line PD-1 blockade plus chemotherapy or chemotherapy from two phase 3 trials (CameL and CameL-sq)
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Poor outcome in postpartum breast cancer patients is associated with distinct molecular and immunological features. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-14 Hanne Lefrère,Kat Moore,Giuseppe Floris,Joyce Sanders,Iris M Seignette,Tycho Bismeijer,Dennis Peters,Annegien Broeks,Erik Hooijberg,Kristel Van Calsteren,Patrick Neven,Ellen Warner,Fedro Alessandro Peccatori,Sibylle Loibl,Charlotte Maggen,Sileny N Han,Katarzyna J Jerzak,Daniela Annibali,Diether Lambrechts,Karin E de Visser,Lodewyk Wessels,Liesbeth Lenaerts,Frédéric Amant
PURPOSE Postpartum breast cancer patients diagnosed after cessation of breastfeeding (post-weaning, PP-BCPW), have a particularly poor prognosis compared to patients diagnosed during lactation (PP-BCDL), or to pregnant (Pr-BC) and nulliparous (NP-BC) patients, irrespective of standard prognostic characteristics. Animal studies point to a role of the involution process in stimulation of tumor growth
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MEDI0457 Plus Durvalumab in HPV-associated HNSCC-Letter. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-14 Keita Mori,Akifumi Notsu,Keita Miura,Yusuke Onozawa
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MEDI0457 Plus Durvalumab in HPV-associated HNSCC-Response. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-14 Charu Aggarwal,Maozhen Gong,Rakesh Kumar
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Editor's Note: Reduced miR-128 in Breast Tumor-Initiating Cells Induces Chemotherapeutic Resistance via Bmi-1 and ABCC5. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-14 Yinghua Zhu,Fengyan Yu,Yu Jiao,Juan Feng,Wei Tang,Herui Yao,Chang Gong,Jianing Chen,Fengxi Su,Yan Zhang,Erwei Song
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Considerations for Drug Development in Myelodysplastic Syndromes. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-14 Mikkael A Sekeres,Nina Kim,Amy E DeZern,Kelly J Norsworthy,Jacqueline S Garcia,R Angelo de Claro,Marc R Theoret,Emily Y Jen,Lori A Ehrlich,Amer M Zeidan,Rami S Komrokji
Myelodysplastic syndromes (MDS) have historically been challenging diseases for drug development due to their biology, preclinical modeling, and the affected patient population. In April 2022, the FDA convened a panel of regulators and academic experts in MDS to discuss approaches to improve MDS drug development. The panel reviewed challenges in MDS clinical trial design and endpoints and outlined
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ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-13 Lenka Stolarova,Petra Kleiblova,Petra Zemankova,Barbora Stastna,Marketa Janatova,Jana Soukupova,Maria Isabel Achatz,Christine Ambrosone,Paraskevi Apostolou,Banu K Arun,Paul Auer,Mollie Barnard,Birgitte Bertelsen,,Marinus J Blok,Nicholas Boddicker,Joan Brunet,Elizabeth S Burnside,Mariarosaria Calvello,Ian Campbell,Sock Hoai Chan,Fei Chen,Jian Bang Chiang,Anna Coppa,Laura Cortesi,Ana Crujeiras-González
PURPOSE Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT). EXPERIMENTAL DESIGN We collected 460 CHEK2 missense
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Dual role of CXCL8 in maintaining the mesenchymal state of glioblastoma stem cells and M2-like tumor-associated macrophages. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-13 Wei Yuan,Qian Zhang,Danling Gu,Chenfei Lu,Deobrat Dixit,Ryan C Gimple,Yisu Gao,Jiancheng Gao,Daqi Li,Danyan Shan,Lang Hu,Lu Li,Yangqing Li,Shusheng Ci,Hao You,Linping Yan,Kexin Chen,Ningwei Zhao,Chuanhai Xu,Jianyun Lan,Dong Liu,Junxia Zhang,Zhumei Shi,Qiulian Wu,Kailin Yang,Linjie Zhao,Zhixin Qiu,Deguan Lv,Wei Gao,Hui Yang,Fan Lin,Qianghu Wang,Jianghong Man,Chaojun Li,Weiwei Tao,Sameer Agnihotri,Xu
PURPOSE The dynamic interplay between glioblastoma stem cells (GSC) and tumor-associated macrophages (TAM) sculpts the tumor immune microenvironment (TIME) and promotes malignant progression of glioblastoma (GBM). However, the mechanisms underlying this interaction are still incompletely understood. Here, we investigate the role of CXCL8 in the maintenance of the mesenchymal state of glioblastoma stem
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A Phase 1b trial of AVID200, a TGFβ 1/3 trap, in patients with myelofibrosis. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-13 John Mascarenhas,Anna Rita Migliaccio,Heidi Kosiorek,Rupali Bhave,Jeanne Palmer,Andrew Kuykendall,Ruben Mesa,Raajit K Rampal,Aaron T Gerds,Abdulraheem Yacoub,Kristen Pettit,Moshe Talpaz,Rami Komrokji,Marina Kremyanskaya,Agapito Gonzalez,Frank Fabris,Kathryn Johnson,Mikaela Dougherty,Erin McGovern,Juan Arango Ossa,Dylan Domenico,Noushin Farnoud,Rona Singer Weinberg,Amy Kong,Vesna Najfeld,Alessandro
PURPOSE Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by systemic symptoms, cytopenias, organomegaly, and bone marrow fibrosis. JAK2 inhibitors afford symptom and spleen burden reduction but do not alter the disease course and frequently lead to thrombocytopenia. TGF-β, a pleiotropic cytokine elaborated by the MF clone, negatively regulates normal hematopoiesis, down-regulates
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Neoadjuvant Cabazitaxel Plus Abiraterone/Leuprolide Acetate in High-Risk Prostate Cancer Patients: ACDC-RP Phase II Trial. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-13 Neil E Fleshner,Rashid K Sayyid,Aaron R Hansen,Joseph L K Chin,Ricardo Fernandes,Eric Winquist,Theodorus van der Kwast,Joan Sweet,Katherine Lajkosz,Miran Kenk,Karen Hersey,Rosette Veloso,Doron Berlin,Jaime O Herrera-Caceres,Srikala Sridhar,Madeleine Moussa,Antonio Finelli,Robert J Hamilton,Girish S Kulkarni,Alexandre R Zlotta,Anthony M Joshua
PURPOSE Early treatment intensification with neoadjuvant therapy may improve outcomes in high-risk, localized prostate cancer (PCa) patients treated with radical prostatectomy (RP). Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to RP in localized, high-risk PCa patients. PATIENTS AND
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Evaluation of somatic mutations in urine samples as a non-invasive method for the detection and molecular classification of endometrial cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-13 Laura Costas,Irene Onieva,Beatriz Pelegrina,Fátima Marin,Alvaro Carmona,Marta López-Querol,Jon Frias-Gomez,Paula Peremiquel-Trillas,José Manuel Martínez,Eduard Dorca,Joan Brunet,Marta Pineda,Jordi Ponce,Xavier Matías-Guiu,Silvia de Sanjosé,Francesc Xavier Bosch,Laia Alemany,Sonia Paytubi
PURPOSE Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive procedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate endometrial cancer patients from controls. EXPERIMENTAL DESIGN Overall, 72 samples were analyzed using next-generation sequencing with molecular identifiers targeting 47 genes. We
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Development and multicenter case-control validation of urinary comprehensive genomic profiling for urothelial carcinoma diagnosis, surveillance, and risk prediction. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-13 Keyan Salari,Debasish Sundi,Jason J Lee,Shulin Wu,Chin-Lee Wu,Gabrielle DiFiore,Q Robert Yan,Andrew Pienkny,Chi K Lee,Daniel Oberlin,Greg Barme,Joel Piser,Robert Kahn,Edward Collins,Kevin G Phillips,Vincent M Caruso,Mahdi Goudarzi,Monica Garcia-Ransom,Peter S Lentz,Martha E Evans-Holm,Andrew R MacBride,Daniel S Fischer,Iden J Haddadzadeh,Brian C Mazzarella,Joe W Gray,Theresa M Koppie,Vincent T Bicocca
PURPOSE Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma (UC) and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. EXPERIMENTAL DESIGN This is a multicenter case-control study utilizing banked urine specimens collected
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Mutual ATRaction: Assessing synergy of berzosertib with sacituzumab govitecan. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-13 Stephanie A Berg,Atish D Choudhury
A phase 1 trial of the novel combination of the ATR inhibitor, berzosertib, plus the antibody-drug conjugate, sacituzumab govitecan, in patients with heavily pre-treatment tumors demonstrated some anti-tumor activity and no dose-limiting toxicities. This represents a new treatment paradigm which will be further explored in a phase 2 setting.
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BCR/integrin interaction in CLL: a physiological remnant with clinical relevance. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-13 Erika Tissino,Riccardo Bomben,Valter Gattei,Antonella Zucchetto
CD49d, the alpha chain of the VLA-4 integrin, has a negative prognostic impact in CLL treated with the BTK-inhibitors ibrutinib and acalabrutinib. Despite BTK inhibition, VLA-4 remains inside-out activated via BCR, an activation dampened by PI3K-inhibitors. Evaluation of CD49d expression in patients starting BTK-inhibitor therapy may improve their prognostic stratification.
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Circulating tumor DNA to drive treatment in metastatic colorectal cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-12 Giorgio Patelli,Gianluca Mauri,Federica Tosi,Alessio Amatu,Katia Bencardino,Erica Bonazzina,Elio Gregory Pizzutilo,Federica Villa,Gabriele Calvanese,Alberto Giuseppe Agostara,Stefano Stabile,Silvia Ghezzi,Giovanni Crisafulli,Federica Di Nicolantonio,Silvia Marsoni,Alberto Bardelli,Salvatore Siena,Andrea Sartore-Bianchi
In the evolving molecular treatment landscape of metastatic colorectal cancer (mCRC), the identification of druggable alterations is pivotal to achieve the best therapeutic opportunity for each patient. Since the number of actionable targets is expanding, there is the need to timely detect their presence or emergence to guide the choice of different available treatment options. Liquid biopsy, through
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A Novel HOXA10-Associated 5 Gene-Based Prognostic Signature for Stratification of Short-Term Survivors of Pancreatic Ductal Adenocarcinoma. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-11 Sophia G Kisling,Pranita Atri,Ashu Shah,Jesse L Cox,Sunandini Sharma,Lynette M Smith,Dario Ghersi,Surinder K Batra
PURPOSE Despite the significant association of molecular subtypes with poor prognosis in pancreatic ductal adenocarcinoma (PDAC) patients, little effort has been made to identify the underlying pathway(s) responsible for this prognosis. Identifying a clinically relevant prognosis-based gene signature may be the key to improving patient outcomes. EXPERIMENTAL DESIGN We analyzed the transcriptomic profiles
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Clinical and molecular features of long-term response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-11 Rohit Thummalapalli,Biagio Ricciuti,Chaitanya Bandlamudi,Daniel Muldoon,Hira Rizvi,Arielle Elkrief,Jia Luo,Joao V Alessi,Federica Pecci,Giuseppe Lamberti,Alessandro Di Federico,Lingzhi Hong,Jianjun Zhang,John V Heymach,Don L Gibbons,Andrew J Plodkowski,Vignesh Ravichandran,Mark T A Donoghue,Chad Vanderbilt,Marc Ladanyi,Charles M Rudin,Mark G Kris,Gregory J Riely,Jamie E Chaft,Matthew D Hellmann,Natalie
PURPOSE We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICIs), and how these might differ from features predictive of short-term response (STR). EXPERIMENTAL DESIGN We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs over ten years. LTR and
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Caveolin gene expression predicts clinical outcomes for early-stage HER2-negative breast cancer treated with paclitaxel-based chemotherapy in the GeparSepto trial. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-11 Terence M Williams,Andreas Schneeweiss,Christian Jackisch,Changxian Shen,Karsten E Weber,Peter A Fasching,Carsten Denkert,Jenny Furlanetto,Ernst Heinmöller,Sabine Schmatloch,Thomas Karn,Christopher W Szeto,Marion T van Mackelenbergh,Valentina Nekljudova,Elmar Stickeler,Patrick Soon-Shiong,Christian Schem,Thomas Mairinger,Volkmar Müller,Frederik Marme,Michael Untch,Sibylle Loibl
BACKGROUND Caveolin-1 and -2 (CAV1/2) dysregulation are implicated in driving cancer progression and may predict response to nab-paclitaxel. We explored the prognostic and predictive potential of CAV1/2 expression for early-stage HER2-negative (HER-) breast cancer (BC) patients receiving neoadjuvant paclitaxel-based chemotherapy regimens. PATIENTS AND METHODS We correlated tumor CAV1/2 RNA expression
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Beyond Neoantigens: Antigens Derived from Tumor Drivers as Cancer Vaccine Targets. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-10 Erika J Crosby,Zachary C Hartman,Herbert Kim Lyerly
A vaccine targeting HER2, a non-mutated but overexpressed tumor antigen, readily primed T-cells for ex vivo expansion and adoptive transfer with minimal toxicity. This regimen led to intramolecular epitope spreading in a majority of patients and offers a treatment modality that may improve outcomes for patients with metastatic breast cancer expressing HER2.
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PET imaging of nectin-4: A promising tool for personalized/precision oncology. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-07 Dawei Jiang,Xiaoli Lan,Weibo Cai
In a recent study, the authors developed a nectin-4-targeting bicyclic peptide-based radiotracer, 68Ga-N188, for PET imaging of advanced urothelial cancer. Preclinical investigation and first-in-human study in 14 patients demonstrated excellent specificity and sensitivity of 68Ga-N188 in detecting metastases. These promising results support 68Ga-N188 as a companion diagnostic for future personalized
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A prognostic model based on residual cancer burden and tumor-infiltrating lymphocytes on residual disease after neoadjuvant therapy in HER2+ breast cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-07 Federica Miglietta,Moira Ragazzi,Bethania Fernandes,Gaia Griguolo,Davide Massa,Fabio Girardi,Michele Bottosso,Alessandra Bisagni,Giovanni Zarrilli,Francesca Porra,Daniela Iannaccone,Leocadia Dore,Mariangela Gaudio,Giacomo Santandrea,Matteo Fassan,Marcello Lo Mele,Rita De Sanctis,Alberto Zambelli,Giancarlo Bisagni,Valentina Guarneri,Maria Vittoria Dieci
PURPOSE We aim to evaluate the prognostic significance of tumor-infiltrating lymphocyte on residual disease (RD-TIL) in HER2+ breast cancer (BC) patients who failed to achieve pathologic-complete response (pCR) after anti-HER2+chemotherapy (CT)-based neoadjuvant treatment (NAT). We assessed the feasibility of combining the prognostic information provided by residual cancer burden (RCB) and RD-TILs
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CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-06 Jordan L Kohlmeyer,Joshua J Lingo,Courtney A Kaemmer,Amanda Scherer,Akshaya Warrier,Ellen Voigt,Juan A Raygoza Garay,Gavin R McGivney,Qierra R Brockman,Amy Tang,Ana Calizo,Kai Pollard,Xiaochun Zhang,Angela C Hirbe,Christine A Pratilas,Mariah Leidinger,Patrick Breheny,Michael S Chimenti,Jessica C Sieren,Varun Monga,Munir R Tanas,David K Meyerholz,Benjamin W Darbro,Rebecca D Dodd,Dawn E Quelle
PURPOSE Malignant peripheral nerve sheath tumors (MPNSTs) are lethal, Ras-driven sarcomas that lack effective therapies. We investigated effects of targeting CDK4/6, MEK, and/or programmed death-ligand 1 (PD-L1) in preclinical MPNST models. EXPERIMENTAL DESIGN Patient-matched MPNSTs and precursor lesions were examined by FISH, RNAseq, IHC, and Connectivity-Map analyses. Antitumor activity of CDK4/6
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Combined CDK4/6 and ERK1/2 inhibition enhances anti-tumor activity in NF1-associated plexiform neurofibroma. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-05 Alyssa C Flint,Dana K Mitchell,Steven P Angus,Abbi E Smith,Waylan Bessler,Li Jiang,Henry Mang,Xiaohong Li,Qingbo Lu,Brooke Rodriguez,George E Sandusky,Andi R Masters,Chi Zhang,Pengtao Dang,Jenna Koenig,Gary L Johnson,Weihua Shen,Jiangang Liu,Amit Aggarwal,Gregory P Donoho,Melinda D Willard,Shripad V Bhagwat,D Wade Clapp,Steven D Rhodes
PURPOSE Plexiform neurofibromas (PNF) are peripheral nerve sheath tumors that cause significant morbidity in persons with neurofibromatosis type 1 (NF1), yet treatment options remain limited. To identify novel therapeutic targets for PNF, we applied an integrated multi-omic approach to quantitatively profile kinome enrichment in a mouse model that has predicted therapeutic responses in clinical trials
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Determinants of survival in HER2+ metastatic esophagogastric cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-05 Steven B Maron,Walid Chatila,Henry Walch,Joanne F Chou,Nicholas Ceglia,Ryan Ptashkin,Richard Kinh Gian Do,Viktoriya Paroder,Neeta Pandit-Taskar,Jason S Lewis,TIago Biachi De Castria,Shalom Sabwa,Fiona Socolow,Lara Feder,Jasmine Thomas,Isabell Schulze,Kwanghee Kim,Arijh Elzein,Viktoria Bojilova,Matthew Zatzman,Umesh Bhanot,Rebecca J Nagy,Jeeyun Lee,Marc Simmons,Michal Segal,Geoffrey Y Ku,David H Ilson
PURPOSE We report updated clinical outcomes from a phase II study of pembrolizumab, trastuzumab, and chemotherapy (PTC) in metastatic esophagogastric (EG) cancer in conjunction with outcomes from an independent MSK cohort. EXPERIMENTAL DESIGN The significance of pre-treatment 89Zr-trastuzumab PET, plasma circulating tumor DNA (ctDNA) dynamics, and tumor HER2 expression and whole exome sequencing was
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FDA Approval Summary: Axicabtagene Ciloleucel for Second-Line Treatment of Large B-cell Lymphoma. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-05 Poornima Sharma,Yvette L Kasamon,Xue Lin,Zhenzhen Xu,Marc R Theoret,Tejashri Purohit-Sheth
In April 2022, the U.S. FDA approved axicabtagene ciloleucel for adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Approval was based on ZUMA-7, a randomized (1:1), open-label trial in 359 patients with primary refractory LBCL (74%) or early relapse who were transplant candidates. The study
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Anticoagulants Enhance Molecular and Cellular Immunotherapy of Cancer by Improving Tumor Microcirculation Structure and Function and Redistributing Tumor Infiltrates. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-05 Fang Wei,Yuling Su,Yibo Quan,Xiaojia Li,Qi Zou,Liuxi Zhang,Shu Li,Mengmeng Jiang,Guohuan Lin,Ping Liang,Jie He,Keping Xie
PURPOSE Pancreatic ductal adenocarcinoma (PDA) resists immunotherapy of adoptive cell transfer (ACT) and immune checkpoint inhibitors. Understanding the mechanisms underlying this resistance will improve PDA immunotherapy. This study investigated therapeutic effects and underlying mechanisms of anticoagulants on immunotherapy in PDA. EXPERIMENTAL DESIGN The antitumor activity of immunotherapy was evaluated
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Phase I trial of ganitumab plus dasatinib to cotarget the insulin-like growth factor 1 receptor and Src family kinase YES in rhabdomyosarcoma. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-07-03 Srivandana Akshintala,R Taylor Sundby,Donna Bernstein,John W Glod,Rosandra N Kaplan,Marielle E Yohe,Andrea M Gross,Joanne Derdak,Haiyan Lei,Alexander Pan,Eva Dombi,Isabel Palacio-Yance,Kailey R Herrera,Markku M Miettinen,Helen X Chen,Seth M Steinberg,Lee J Helman,Leo Mascarenhas,Brigitte C Widemann,Fariba Navid,Jack F Shern,Christine M Heske
PURPOSE Antibodies against IGF-1R have shown meaningful but transient tumor responses in patients with rhabdomyosarcoma (RMS). The SRC family member YES has been shown to mediate IGF-1R antibody acquired resistance, and cotargeting IGF-1R and YES resulted in sustained responses in murine RMS models. We conducted a phase I trial of the anti-IGF-1R antibody ganitumab combined with dasatinib, a multi-kinase
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Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-30 Jonathan M J Derry,Connor Burns,Jason P Frazier,Emily Beirne,Marc Grenley,Christopher C DuFort,Emily Killingbeck,Michael Leon,Claire Williams,Mark Gregory,Jeffrey Houlton,Daniel Clayburgh,Paul Swiecicki,Dennis Huszar,Allison Berger,Richard A Klinghoffer
PURPOSE Cancer drug development is currently limited by a paradigm of preclinical evaluation that does not adequately recapitulate the complexity of the intact human tumor microenvironment (TME). To overcome this, we combined trackable intratumor microdosing (CIVOTM) with spatial biology readouts to directly assess drug effects in patient tumors in situ. PATIENTS AND METHODS In a first-of-its-kind
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Results of an Open-label, Phase 1a/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced or Metastatic Soft Tissue Sarcoma. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-29 Patrick Schöffski,Rastislav Bahleda,Andrew J Wagner,Melissa A Burgess,Niels Junker,Michael Chisamore,Patrick Peterson,Anna M Szpurka,Matteo Ceccarelli,William D Tap
PURPOSE The study evaluated safety and efficacy of olaratumab+pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma with disease progression on standard treatment. PATIENTS AND METHODS This was open-label, multicenter, nonrandomized, phase 1a/1b dose-escalation study followed by cohort expansion (olaratumab+pembrolizumab intravenous infusion). Primary objectives
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De novo and histologically transformed small cell lung cancer is sensitive to lurbinectedin treatment through the modulation of EMT and NOTCH signaling pathways. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-29 Subhamoy Chakraborty,Charles Coleman,Parvathy Manoj,Deniz Demircioglu,Nisargbhai Shah,Elisa de Stanchina,Charles M Rudin,Dan Hasson,Triparna Sen
PURPOSE Small cell lung cancer (SCLC) is a high-grade neuroendocrine tumor with dismal prognosis and limited treatment options. Lurbinectedin, conditionally approved as a second-line treatment for metastatic SCLC, drives clinical responses in about 35% of patients and the overall survival of those who benefit from it remains very low (~9.3 months). This highlights the need to develop improved mechanistic
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Impact of Frontline Ivosidenib on Volumetric Growth Patterns in Isocitrate Dehydrogenase (IDH) mutant Astrocytic and Oligodendroglial Tumors. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-29 David Olayinka Kamson,Sushant Puri,Yingying Sang,Meihui Jessica Shi,Lindsay Blair,Jaishri O Blakeley,John Laterra
PURPOSE Isocitrate dehydrogenase (IDH) mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients' most productive years. We report our experience using off-label first-inclass IDH1mut-inhibitor ivosidenib and its impact on tumor volume in IDHmut gliomas. EXPERIMENTAL DESIGN We retrospectively analyzed patients aged ≥18
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Dissecting the mechanisms underlying the Cytokine Release Syndrome (CRS) mediated by T Cell Bispecific Antibodies. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-28 Gabrielle Leclercq-Cohen,Nathalie Steinhoff,Llucia Albertí-Servera,Sina Nassiri,Sabrina Danilin,Emily Piccione,Emilio Yángüez,Tamara Hüsser,Sylvia Herter,Stephan Schmeing,Petra Gerber,Petra Schwalie,Johannes Sam,Stefanie Briner,Sylvia Jenni,Roberta Bianchi,Marlene Biehl,Floriana Cremasco,Katerina Apostolopoulou,Hélène Haegel,Christian Klein,Pablo Umana,Marina Bacac
PURPOSE Target-dependent TCB activity can result in strong and systemic release of cytokines that may develop into Cytokine Release Syndrome (CRS), highlighting the need to understand and prevent this complex clinical syndrome. EXPERIMENTAL DESIGN We explored the cellular and molecular players involved in TCB-mediated cytokine release by single cell RNA sequencing of whole blood treated with CD20-TCB
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Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non-Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-28 Jhanelle E Gray,Myung-Ju Ahn,Geoffrey R Oxnard,Frances A Shepherd,Fumio Imamura,Ying Cheng,Isamu Okamoto,Byoung Chul Cho,Meng-Chih Lin,Yi-Long Wu,Margarita Majem,Oliver Gautschi,Michael Boyer,Krishna C Bulusu,Aleksandra Markovets,J Carl Barrett,Rachel Hodge,Astrid McKeown,Ryan J Hartmaier,Juliann Chmielecki,Vassiliki A Papadimitrakopoulou,Suresh S Ramalingam
PURPOSE Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non-small cell lung cancer (NSCLC); monitoring dynamic ctDNA changes may be used to predict outcomes. EXPERIMENTAL DESIGN This was a retrospective, exploratory analysis of two phase III trials (AURA3 [NCT02151981], FLAURA [NCT02296125]). All patients had epidermal growth factor receptor mutation-positive (ex19del
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PD1 monotherapy reigns supreme in adjuvant melanoma…but for how long? Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-28 Ryan C Augustin,Jason J Luke
The results of CheckMate-238 led to the original FDA approval of anti-PD1 therapy in high-risk, resectable melanoma. In this CCR Translations, we discuss the 5-year update of this pivotal trial and contextualize its results in the face of limited survival data, neoadjuvant therapy, next-generation biomarkers, and novel immunotherapy combinations.
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Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-28 Espen B Ellingsen,Steven O'Day,Artur Mezheyeuski,Agnieszka Gromadka,Trevor Clancy,Timothy S Kristedja,Mohammed Milhem,Yousef Zakharia
PURPOSE Cancer vaccines represent a novel treatment modality with a complementary mode of action addressing a crucial bottleneck for checkpoint inhibitor (CPI) efficacy. CPIs are expected to release brakes in T-cell responses elicited by vaccination, leading to more robust immune responses. Increased anti-tumor T-cell responses may confer increased anti-tumor activity in patients with less immunogenic
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Driving Diversity and Inclusion in Cancer Drug Development - Industry and Regulatory Perspectives, Current Practices, Opportunities, and Challenges. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-28 Lola A Fashoyin-Aje,Craig Tendler,Bea Lavery,Serban Ghiorghiu,Brittany Gerald,Chitkala Kalidas,Nicole Richie,Kathleen Winson,Nicholas J H Warren,Tristen V Tellman,Jon Retzlaff,Margaret Foti,Richard Pazdur
In April 2022, the FDA issued draft guidance to help industry develop strategies to improve diversity in clinical trials. Historically, clinical trial sponsors have not systematically incorporated efforts to promote diversity, equity, and inclusion (DEI), particularly during the early design stages of clinical development plans and operational strategies. Unfortunately, a retrospective approach to
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Phase 1 Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-26 Mark Roschewski,Manish R Patel,Patrick M Reagan,Nakhle S Saba,Graham P Collins,Hendrik-Tobias Arkenau,Sven de Vos,Barret Nuttall,Melih Acar,Kathleen Burke,Rafael D White,Maria Udriste,Shringi Sharma,Brian Dougherty,Daniel Stetson,David Jenkins,Andrew Mortlock,Alessandra Forcina,Veerendra Munugalavadla,Ian Flinn
BACKGROUND Novel targeted and immunotherapies have improved outcomes in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but toxicities limit widespread use. The selective Bruton tyrosine kinase (BTK) inhibitor acalabrutinib has activity in patients with R/R DLBCL, but durable responses are uncommon. STAT3 inhibition has demonstrated clinical activity in DLBCL. METHODS Final results
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Genomic profiling of metastatic castration-resistant prostate cancer samples resistant to androgen-receptor pathway inhibitors. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-26 Naoual Menssouri,Loic Poiraudeau,Carole Helissey,Ludovic Bigot,Jonathan Sabio,Tony Ibrahim,Cedric Pobel,Claudio Nicotra,Maud Ngo-Camus,Ludovic Lacroix,Etienne Rouleau,Lambros Tselikas,Anne Chauchereau,Félix Blanc-Durand,Alice Bernard-Tessier,Anna Patrikidou,Natacha Naoun,Ronan Flippot,Emeline Colomba,Alina Fuerea,Laurence Albiges,Pernelle Lavaud,Paul van de Wiel,Eveline den Biezen-Timmermans,Yvonne
PURPOSE The androgen receptor axis inhibitors (ARPI) (e.g, enzalutamide, abiraterone acetate) are administered in daily practice for men with metastatic castration-resistant prostate cancer (mCRPC). However, not all patients respond, and mechanisms of both primary and acquired resistance remain largely unknown Experimental Design: In a prospective trial MATCH-R (NCT02517892), 59 mCRPC patients underwent
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Associations between AI-assisted tumor amphiregulin and epiregulin IHC and outcomes from anti-EGFR therapy in the routine management of metastatic colorectal cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-26 Christopher J M Williams,Faye Elliott,Nancy Sapanara,Faranak Aghaei,Liping Zhang,Andrea Muranyi,Dongyao Yan,Isaac Bai,Zuo Zhao,Michael Shires,Henry M Wood,Susan D Richman,Gemma Hemmings,Michael Hale,Daniel Bottomley,Leanne Galvin,Caroline Cartlidge,Sarah Dance,Chris M Bacon,Laura Mansfield,Kathe Young-Zvandasara,Ajay Sudan,Katy Lambert,Irena Bibby,Sarah E Coupland,Amir Montazeri,Natalie Kipling,Kathryn
PURPOSE High tumor production of the EGFR ligands, amphiregulin (AREG) and epiregulin (EREG), predicted benefit from anti-EGFR therapy for metastatic colorectal cancer (mCRC) in a retrospective analysis of clinical trial data. Here, AREG/EREG immunohistochemistry (IHC) was analyzed in a cohort of patients who received anti-EGFR therapy as part of routine care, including key clinical contexts not investigated
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Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-26 Ana Oaknin,Bhavana Pothuri,Lucy Gilbert,Renaud Sabatier,Jubilee Brown,Sharad Ghamande,Cara Mathews,David M O'Malley,Rebecca Kristeleit,Valentina Boni,Adriano Gravina,Susana Banerjee,Rowan Miller,Joanna Pikiel,Mansoor R Mirza,Ninad Dewal,Grace Antony,Yuping Dong,Eleftherios Zografos,Jennifer Veneris,Anna V Tinker
PURPOSE This interim report of the GARNET phase I trial presents efficacy and safety of dostarlimab in patients with advanced or recurrent endometrial cancer (EC), with an analysis of tumor biomarkers as prognostic indicators. PATIENTS AND METHODS A total of 153 patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and 161 patients with mismatch repair proficient (
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Efficacy and quality-of-life following involved nodal radiotherapy for head and neck squamous cell carcinoma: the INRT-AIR phase II clinical trial. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-26 David J Sher,Dominic H Moon,Dat Vo,Jing Wang,Liyuan Chen,Michael Dohopolski,Randall Hughes,Baran D Sumer,Chul Ahn,Vladimir Avkshtol
PURPOSE Elective neck irradiation (ENI) has long been considered mandatory when treating head and neck squamous cell carcinoma (HNSCC) with definitive radiotherapy, but it is associated with significant dose to normal organs-at-risk (OAR). In this prospective phase II study, we investigated the efficacy and tolerability of eliminating ENI and strictly treating involved and suspicious lymph nodes (LN)
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Dual targeting of apoptotic and signaling pathways in T-lineage acute lymphoblastic leukemia. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-26 Caner Saygin,Giorgia Giordano,Kathryn Shimamoto,Bart Eisfelder,Anika Thomas-Toth,Girish Venkataraman,Vijayalakshmi Ananthanarayanan,Tiffaney L Vincent,Adam DuVall,Anand A Patel,Yi Chen,Fenlai Tan,Stephen P Anthony,Yu Chen,Yue Shen,Olatoyosi Odenike,David T Teachey,Barbara L Kee,James LaBelle,Wendy Stock
PURPOSE Relapsed T-acute lymphoblastic leukemia (T-ALL) has limited treatment options. We investigated mechanisms of resistance to BH3 mimetics in T-ALL in order to develop rational combination strategies. We also looked at the preclinical efficacy of NWP-0476, a novel BCL-2/BCL-xL inhibitor, as single agent and combination therapy in T-ALL. METHODS We used BH3 profiling as a predictive tool for BH3
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Safety and efficacy of tucatinib, letrozole and palbociclib in patients with previously treated HR+/HER2+ breast cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-26 Elena Shagisultanova,William Gradishar,Ursa Brown-Glabberman,Pavani Chalasani,Andrew J Brenner,Alison Stopeck,Hannah Parris,Dexiang Gao,Tessa Mcspadden,Jose Mayordomo,Jennifer R Diamond,Peter Kabos,Virginia F Borges
PURPOSE To overcome resistance to anti-hormonal and HER2-targeted agents mediated by cyclin D1-CDK4/6 complex, we proposed an oral combination of the HER2 inhibitor Tucatinib, aromatase inhibitor Letrozole, and CDK4/6 inhibitor Palbociclib (TLP) for treatment of HR+/HER2+ metastatic breast cancer (MBC). PATIENTS AND METHODS Phase Ib/II TLP trial (NCT03054363) enrolled patients with HR+/HER2+ MBC treated
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Assessment of Homologous Recombination Deficiency in Ovarian Cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-22 Vikas Garg,Amit M Oza
Accurately assessing homologous recombination deficiency to use as predictive biomarker is an area of intense research in ovarian cancer. Validated assays have demonstrated utility in determining maintenance therapy following platinum sensitive chemotherapy. Novel functional assays promise the potential to reflect HRD in real time and predict response to PARP inhibitors.
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A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-21 David Levitz,Yogen Saunthararajah,Kateryna Fedorov,Lauren C Shapiro,Ioannis Mantzaris,Aditi Shastri,Noah Kornblum,R Alejandro Sica,Nishi Shah,Marina Konopleva,Kira Gritsman,Ira Braunschweig,Dennis L Cooper,Kith Pradhan,Amit Verma,Eric J Feldman,Mendel Goldfinger
PURPOSE Venetoclax (VEN) added to the hypomethylating agents (HMA) decitabine or azacitidine is the new standard of care for elderly patients with acute myeloid leukemia (AML) and is being evaluated in myelodysplastic syndrome (MDS). Current dosing of HMA/VEN relies on leukemia suppression through cytotoxicity which also impacts normal hematopoiesis. A regimen using once-weekly low-dose decitabine
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Discovery and targeting of a noncanonical mechanism of sarcoma resistance to ADI-PEG20 mediated by the microenvironment. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-20 Leonard C Rogers,Jeff C Kremer,Caitlyn B Brashears,Zongtao Lin,Zhixian Hu,Alliny C S Bastos,Adriana Baker,Nicole Fettig,Dong Zhou,Kooresh I Shoghi,Carina A Dehner,John S A Chrisinger,John S Bomalaski,Benjamin A Garcia,Toshinao Oyama,Eileen P White,Brian A Van Tine
PURPOSE Many cancers lack argininosuccinate synthetase 1 (ASS1), the rate limiting enzyme of arginine biosynthesis. This deficiency causes arginine auxotrophy, targetable by extracellular arginine-degrading enzymes such as ADI-PEG20. Long-term tumor resistance has thus far been attributed solely to ASS1 re-expression. This study examines the role of ASS1 silencing on tumor growth and initiation and
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The prognostic effect of immune cell infiltration depends on molecular subtype in Endometrioid Ovarian Carcinomas. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-20 Karolin Heinze,Evan S Cairns,Shelby Thornton,Bronwyn Harris,Katy Milne,Marcel Grube,Charlotte Meyer,Anthony N Karnezis,Sian Fereday,Dale W Garsed,Samuel C Y Leung,Derek S Chiu,Malak Moubarak,Philipp Harter,Florian Heitz,Jessica N McAlpine,Anna DeFazio,David D L Bowtell,Ellen L Goode,Malcolm Pike,Susan J Ramus,C Leigh Pearce,Annette Staebler,Martin Köbel,Stefan Kommoss,Aline Talhouk,Brad H Nelson,Michael
PURPOSE Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10-20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas (EC) including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, though tumor initiating events remain elusive. There is
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Identifying mechanisms of resistance by circulating tumour DNA in EVOLVE, a Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer at time of PARP Inhibitor Progression. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-16 Stephanie Lheureux,Stephenie D Prokopec,Leslie E Oldfield,Eduardo Gonzalez-Ochoa,Jeff P Bruce,Derek Wong,Arnavaz Danesh,Dax Torti,Jonathan Torchia,Alexander Fortuna,Sharanjit Singh,Matthew Irving,Kayla Marsh,Bernard Lam,Vanessa Speers,Aleksandra Yosifova,Ana Oaknin,Ainhoa Madariaga,Neesha C Dhani,Valerie Bowering,Amit M Oza,Trevor J Pugh
Purpose To evaluate the use of blood cell-free DNA (cfDNA) to identify emerging mechanisms of resistance to PARP inhibitors (PARPi) in high grade serous ovarian cancer (HGSOC). Patients and Methods We used targeted sequencing (TS) to analyse 78 longitudinal cfDNA samples collected from 30 patients with HGSOC enrolled in a phase II clinical trial evaluating cediranib (VEGF inhibitor) plus olaparib (PARPi)
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-----Gold nanostars obviate limitations to laser interstitial thermal therapy (LITT) for the treatment of intracranial tumors. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-16 Ethan S Srinivasan,Yang Liu,Ren A Odion,Pakawat Chongsathidkiet,Lucas P Wachsmuth,Aden P Haskell-Mendoza,Ryan M Edwards,Aidan J Canning,Gavin Willoughby,Joseph Hinton,Stephen J Norton,Christopher D Lascola,Paolo F Maccarini,Christopher L Mariani,Tuan Vo-Dinh,Peter E Fecci
PURPOSE Laser interstitial thermal therapy (LITT) is an effective minimally-invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT. EXPERIMENTAL DESIGN The impact of GNS on LITT coverage capacity was tested in ex vivo models utilizing clinical
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Bavituximab decreases immunosuppressive myeloid-derived suppressor cells in newly diagnosed glioblastoma patients. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-16 K Ina Ly,Leland G Richardson,Mofei Liu,Alona Muzikansky,Jonathan Cardona,Kevin Lou,Andrew L Beers,Ken Chang,James M Brown,Xiaoyue Ma,David A Reardon,Isabel C Arrillaga-Romany,Deborah A Forst,Justin T Jordan,Eudocia Q Lee,Jorg Dietrich,Lakshmi Nayak,Patrick Y Wen,Ugonma Chukwueke,Anita Giobbie-Hurder,Bryan D Choi,Tracy T Batchelor,Jayashree Kalpathy-Cramer,William T Curry,Elizabeth R Gerstner
PURPOSE We evaluated the efficacy of bavituximab - a monoclonal antibody with anti-angiogenic and immunomodulatory properties - in newly diagnosed glioblastoma (GBM) patients who also received radiation and temozolomide. Perfusion MRI and myeloid-related gene transcription and inflammatory infiltrates in pre-and post-treatment tumor specimens were studied to evaluate on-target effects (NCT03139916)
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Activin A-mediated polarization of cancer-associated fibroblasts and macrophages confers resistance to checkpoint immunotherapy in skin cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-16 Christine Pich-Bavastro,Laura Yerly,Jeremy Di Domizio,Stéphanie Tissot-Renaud,Michel Gilliet,François Kuonen
PURPOSE Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCCs), however with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy. EXPERIMENTAL DESIGN Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment
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Functional genetic variants in TGF-β1 and TGF-βR1 in microRNA binding sites predict outcomes in patients with HPV-positive oropharyngeal squamous cell carcinoma. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-16 Zihao Niu,Peng Sun,Hongliang Liu,Peng Wei,Jia Wu,Zhigang Huang,Neil D Gross,Sanjay Shete,Qingyi Wei,Mark E Zafereo,George A Calin,Guojun Li
PURPOSE TGF-β1 and TGF-βR1 participate in regulation of the host's immune system and inflammatory responses and may serve as prognostic biomarkers for HPV-associated OPSCC. EXPERIMENTAL DESIGN This study included 1013 patients with incident OPSCC, of whom 489 had tumor HPV16 status determined. All patients were genotyped for two functional polymorphisms: TGF-β1 rs1800470 and TGF-βR1 rs334348. Univariate
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Facts and hopes in colorectal cancer immunotherapy. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-16 Michael B Foote,Guillem Argiles,Benoit Rousseau,Neil H Segal
Although a minority of colorectal cancers exhibit mismatch-repair deficiency and associated sensitivity to immune checkpoint inhibitors, the vast majority of colorectal cancers arise in a tolerogenic microenvironment with mismatch-repair proficiency, low tumor-intrinsic immunogenicity, and negligible immunotherapy responsiveness. Treatment strategies to augment tumor immunity with combination immune
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FDA Approval Summary: Tucatinib with trastuzumab for advanced unresectable or metastatic, chemotherapy refractory, HER2 positive RAS wild type colorectal cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-15 Sandra J Casak,M Naomi Horiba,Mengdie Yuan,Joyce Cheng,Steven J Lemery,Yuan Li Shen,Wentao Fu,Jason N Moore,Yangbing Li,Youwei Bi,Doris Auth,Nataliya Fesenko,Paul G Kluetz,Richard Pazdur,Lola A Fashoyin-Aje
On January 29, 2023, the FDA granted accelerated approval to tucatinib in combination with trastuzumab for the treatment of patients with unresectable or metastatic RAS wild-type, HER2-positive colorectal cancer who have received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Approval was based on the pooled analysis of patients receiving tucatinib in combination with trastuzumab
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B-cell receptor pathway mutations are infrequent in patients with chronic lymphocytic leukemia on continuous ibrutinib therapy. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-14 Jennifer A Woyach,Paolo Ghia,John C Byrd,Inhye E Ahn,Carol Moreno,Susan M O'Brien,Daniel Jones,Leo W K Cheung,Elizabeth Chong,Kevin Kwei,James P Dean,Danelle F James,Adrian Wiestner
PURPOSE Acquired mutations in Bruton's tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) treated with BTK inhibitors. Data on mutation rates in patients without PD on ibrutinib treatment are limited. EXPERIMENTAL DESIGN We evaluated frequency and time to detection of BTK and PLCG2 mutations
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RETaliation - tackling rare resistance alterations to osimertinib. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-14 Matthew G Krebs,Sanjay Popat
RET fusions occur as a rare mechanism of acquired resistance to osimertinib in epidermal growth factor receptor mutation (EGFRm) positive non-small cell lung cancer (NSCLC) patients. Inhibiting RET alongside osimertinib shows promising clinical activity but innovative approaches are needed to seek regulatory approvals in these rare treatment resistance settings.
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Prognosis to Radiation Unlocked: How Hypoxia Methylome may hold the Key in HNSCC. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-13 Molly E Heft Neal,J Chad Brenner
Hypoxia in head and neck tumors has proven to be predictive of outcomes. Current hypoxia signatures have failed for patient treatment selection. In a recent study, the authors identified a hypoxia methylation signature as a more robust biomarker in HNSCC and shed light into the mechanism of hypoxia-mediated treatment resistance.
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Accessible Data Collections for Improved Decision Making in Neuro-Oncology Clinical Trials. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-13 Rifaquat Rahman,Steffen Ventz,Robert Redd,Timothy Cloughesy,Brian M Alexander,Patrick Y Wen,Lorenzo Trippa
Drug development can be associated with slow timelines, particularly for rare or difficult-to-treat solid tumors such as glioblastoma. The use of external data in the design and analysis of trials has attracted significant interest because it has the potential to improve the efficiency and precision of drug development. A recurring challenge in the use of external data for clinical trials, however
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Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer. Clin. Cancer Res. (IF 11.5) Pub Date : 2023-06-13 Jamie M Sperger,Kyle T Helzer,Charlotte N Stahlfeld,Dawei Jiang,Anupama Singh,Katherine R Kaufmann,David J Niles,Erika Heninger,Nicholas R Rydzewski,Liguo Wang,Liewei Wang,Rendong Yang,Yanan Ren,Jonathan W Engle,Peng Huang,Christos E Kyriakopoulos,Susan F Slovin,Howard R Soule,Shuang G Zhao,Manish Kohli,Scott T Tagawa,Weibo Cai,Scott M Dehm,Joshua M Lang
PURPOSE Men with metastatic castration-resistant prostate cancer (mCRPC) frequently develop resistance to androgen receptor signaling inhibitor (ARSI) treatment; therefore, new therapies are needed. Trophoblastic cell-surface antigen (TROP-2) is a transmembrane protein identified in prostate cancer and overexpressed in multiple malignancies. TROP-2 is a therapeutic target for antibody-drug conjugates