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Anti-4-1BB×PD-L1 Bispecific Antibody Reinvigorates Tumor-Specific Exhausted CD8+ T Cells and Enhances the Efficacy of Anti-PD-1 Blockade Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-14 Seung Hyuck Jeon, Gihoon You, Junsik Park, Youseung Chung, Kyungjin Park, Hyunjoo Kim, Jaehyoung Jeon, Youngkwang Kim, Woo-Chan Son, Da Som Jeong, Eui-Cheol Shin, Jung-Yun Lee, Dai Hoon Han, Jaeho Jung, Su-Hyung Park
Purpose: To overcome the limited efficacy of immune checkpoint blockade, there is a need to find novel cancer immunotherapeutic strategies for the optimal treatment of cancer. The novel anti-4-1BB×PD-L1 bispecific antibody—ABL503 (also known as TJ-L14B)—was designed to simultaneously target PD-L1 and 4-1BB, and demonstrated strong antitumor T-cell responses without considerable toxicity. Here, we investigated
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Project Optimus elicits the "holistic" benefits of PK/PD modeling of immunotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-14 Mathangi Gopalakrishnan, Rodabe N. Amaria
Leveraging a heterogeneous dataset, a recent article demonstrated the application of pharmacometric modeling to inform dosing of nivolumab-relatlimab fixed-dose combination in special populations, including adolescents lacking clinical data. Use of model-informed approaches during clinical drug development can be cost effective, ensuring faster access to drugs, thus enhancing patient outcomes.
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Bystander effects, pharmacokinetics, and linker-payload stability of EGFR-targeting antibody-drug conjugates Losatuxizumab vedotin and Depatux-M in glioblastoma models Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-14 Sonia Jain, Jessica I. Griffith, Kendra A. Porath, Sneha Rathi, Jiayan Le, Tugce I. Pasa, Paul A. Decker, Shiv K. Gupta, Zeng Hu, Brett L. Carlson, Katrina Bakken, Danielle M. Burgenske, Thomas M. Feldsien, Didier R. Lefebvre, Rachael A. Vaubel, Jeanette E. Eckel-Passow, Edward B. Reilly, William F. Elmquist, Jann N. Sarkaria
Purpose: Antibody-drug conjugates (ADCs) are targeted therapies with robust efficacy in solid cancers, and there is intense interest in using EGFR-specific ADCs to target EGFR-amplified glioblastoma (GBM). Given the molecular heterogeneity of GBM, bystander activity of ADCs may be important for determining treatment efficacy. In this study, the activity and toxicity of two EGFR-targeted ADCs, Losatuxizumab
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A proof-of-concept study of sequential treatment with the HDAC inhibitor vorinostat following BRAF and MEK inhibitors in BRAFV600mutated melanoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-13 Alaa Embaby, Sanne C.F.A. Huijberts, Liqin Wang, Rodrigo Leite de Oliveira, Hilde Rosing, Bastiaan Nuijen, Joyce Sanders, Ingrid Hofland, Charlaine van Steenis, Roelof J.C. Kluin, Cor Lieftink, Christopher G. Smith, Christian U. Blank, Johannes V. van Thienen, John B.A.G. Haanen, Neeltje Steeghs, Frans L. Opdam, Jos H. Beijnen, Alwin D.R. Huitema, Rene Bernards, Jan H.M. Schellens, Sofie Wilgenhof
Purpose: Development of resistance limits the clinical benefit of BRAF and MEK inhibitors (BRAFi/MEKi) in BRAFV600 mutated melanoma. It has been shown that short-term treatment (14 days) with vorinostat was able to initiate apoptosis of the resistant tumor cells. We aimed to assess the anti-tumor activity of sequential treatment with vorinostat following BRAFi/MEKi in patients with BRAFV600 melanoma
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Plasma versus tissue tumor mutational burden as biomarkers of durvalumab plus tremelimumab response in patients with metastatic colorectal cancer in the CO.26 trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-10 Jonathan M. Loree, Emma Titmuss, James T. Topham, Hagen F. Kennecke, Harriet Feilotter, Shakeel Virk, Young S. Lee, Kimberly Banks, Katie Quinn, Aly Karsan, Daniel J. Renouf, Derek J. Jonker, Dongsheng Tu, Chris J. O'Callaghan, Eric X. Chen
Purpose: Tissue derived tumor mutation burden (TMB) of ≥10 mutations/Mb is a histology agnostic biomarker for the immune checkpoint inhibitor (ICI) pembrolizumab. However, the dataset on which this was validated lacked colorectal cancers (CRCs), and there is limited evidence for immunotherapy benefit in CRC using this threshold. Patients and Methods: CO.26 was a randomized phase II study of 180 patients
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Biomarker identification and risk prediction model development for differentiated thyroid carcinoma lung metastasis based on primary lesion proteomics Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-09 Xiaoqi Peng, Hongbo Zhao, Lijuan Ye, Fei Hou, Zihan Yi, Yanxin Ren, Lin Lu, Fukun Chen, Juan Lv, Yinghui Wang, Haolin Cai, Xihua Zheng, Qing Yang, Ting Chen
Purpose: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. Experimental Design: Through proteomic
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Phase II Clinical Trial of Intravenous Levothyroxine to Mitigate Pharyngocutaneous Fistula in Euthyroid Patients Undergoing Salvage Laryngectomy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-09 Molly E. Heft Neal, Catherine T. Haring, Emily Bellile, Craig C. Jaffe, Andrew G. Shuman, Steven B. Chinn, Chaz L. Stucken, Kelly M. Malloy, Keith A. Casper, Mark E.P. Prince, Douglas B. Chepeha, Andrew J. Rosko, Matthew E. Spector
Purpose: Patients undergoing head and neck cancer surgery after prior radiation or chemoradiation are at high risk for wound complications. Hypothyroidism is a known risk factor for wound complications, especially fistulae after salvage total laryngectomy. The purpose of this phase II clinical trial is to investigate the effect of peri-operative intravenous levothyroxine supplementation on wound complications
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MYC Inhibition Potentiates CD8+ T Cells Against Multiple Myeloma and Overcomes Immunomodulatory Drug Resistance Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-09 Lorraine N. Davis, Zachary J. Walker, Lauren T. Reiman, Sarah E. Parzych, Brett M. Stevens, Craig T. Jordan, Peter A. Forsberg, Daniel W. Sherbenou
Purpose: Immunomodulatory drugs (IMiDs), such as lenalidomide and pomalidomide, are cornerstone therapies in Multiple Myeloma (MM), yet patients inevitably become refractory. IMiDs exert cytotoxicity through inducing Cereblon-dependent proteasomal degradation of IKZF1 and IKZF3, resulting in downregulation of the oncogenic transcription factors IRF4 and MYC. To date, clinical IMiD resistance independent
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Safety And Efficacy Of Combination Lurbinectedin Plus Doxorubicin From A Phase 1b Trial In Patients With Advanced/Metastatic Soft Tissue Sarcoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-09 Gregory M. Cote, Candace L. Haddox, Edwin Choy, Priscilla A. Merriam, Emanuele Mazzola, Vinayak Venkataraman, Thierry Alcindor, Andrew J. Wagner, George D. Demetri, Suzanne George
Purpose: While cytotoxic chemotherapy is standard first-line treatment for patients with metastatic soft tissue sarcoma (STS), clinical outcomes remain suboptimal. Our prior study showed lurbinectedin plus doxorubicin is well-tolerated with promising clinical activity in STS. We designed this phase 1b trial to optimize dosing as the basis for a randomized trial in leiomyosarcoma (LMS) and to further
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CDKN2A/B homozygous deletion sensitizes IDH-mutant glioma to CDK4/6 inhibition Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-08 Ali M. Nasser, Lisa Melamed, Ethan Wetzel, Chia-Chen Chang, Hiroaki Nagashima, Yosuke Kitagawa, Logan Muzyka, Hiroaki Wakimoto, Daniel P. Cahill, Julie J. Miller
Purpose: Treatment paradigms for Isocitrate dehydrogenase (IDH) mutant gliomas are rapidly evolving. While typically indolent and responsive to initial treatment, these tumors invariably recur at higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcome. We investigated the effect
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Plasma Metabolic Profiles-Based Prediction of Induction Chemotherapy Efficacy in Nasopharyngeal Carcinoma: Results of a Bidirectional Clinical Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-07 Tingxi Tang, Zhenhua Zhou, Min Chen, Nan Li, Jianda Sun, Zekai Chen, Ting Xiao, Xiaoqing Wang, Longshan Zhang, Yingqiao Wang, Hanbin Zhang, Xiuting Zheng, Bei Chen, Feng Ye, Jian Guan
Purpose: The efficacy of induction chemotherapy (IC) as a primary treatment for advanced nasopharyngeal carcinoma (NPC) remains a topic of debate, with a lack of dependable biomarkers for predicting its efficacy. This study seeks to establish a predictive classifier utilizing plasma metabolomics profiling. Experimental design: A total of 166 NPC patients enrolled in the clinical trial NCT05682703 and
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FDA Approval Summary: Ciltacabtagene Autoleucel for Relapsed or Refractory Multiple Myeloma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-07 Kavita Natrajan, Megha Kaushal, Bindu George, Bindu Kanapuru, Marc R. Theoret
In February 2022, the U.S. Food and Drug Administration approved ciltacabtagene autoleucel, a chimeric antigen receptor (CAR) T cell therapy targeting the B-cell maturation antigen (BCMA), for adult patients with relapsed/refractory multiple myeloma (RRMM) after ≥4 lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based
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Antibody Drug Conjugate Sacituzumab Govitecan Enables A Sequential TOP1/PARP Inhibitor Cancer Therapy Strategy in Breast Cancer Patients Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-06 Aditya Bardia, Sheng Sun, Nayana Thimmiah, James T. Coates, Bogang Wu, Rachel O. Abelman, Laura Spring, Beverly Moy, Phoebe Ryan, Mark N. Melkonyan, Ann Partridge, Dejan Juric, Jeffrey Peppercorn, Heather Parsons, Seth A. Wander, Victoria Attaya, Brenda Lormil, Maria Shellock, Aiko Nagayama, Veerle Bossuyt, Steven J. Isakoff, Sara M. Tolaney, Leif W. Ellisen
Purpose: The Antibody-Drug Conjugate (ADC) Sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly (ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1 inhibitors and SG, but previous studies combining systemic PARP and TOP1 inhibitors failed due to dose-limiting myelosuppression
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Phase II study to determine the anti-tumor activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in esophageal cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-06 Hans Prenen, Sanjeev Deva, Bhumsuk Keam, Colin R. Lindsay, Iwona Lugowska, James C. Yang, Federico Longo, Maria de Miguel, Mariano Ponz-Sarvise, Myung-Ju Ahn, Mahmut Gumus, Stephane Champiat, Antoine Italiano, Sebastien Salas, Ruth Perets, Cagatay Arslan, Byoung C. Cho, Stefan Evers, Christophe Boetsch, Daniel Marbach, David Dejardin, Nassim Sleiman, Caroline Ardeshir, Muriel Richard, Jehad Charo,
Purpose: Reported here are results from the esophageal squamous cell carcinoma (SCC) cohort of a Phase II, non-comparative, basket study, evaluating the anti-tumor activity and safety of FAP-IL2v plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721). Experimental design: Eligible patients had an Eastern Cooperative Oncology Group performance status of 0–1; measurable metastatic
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Minimal Residual Disease using a Plasma-Only Circulating Tumor DNA Assay to Predict Recurrence of Metastatic Colorectal Cancer Following Curative Intent Treatment Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-02 Aparna R. Parikh, Bryant H. Chee, Jill Tsai, Thereasa A. Rich, Kristin S. Price, Sonia A. Patel, Li Zhang, Faaiz Ibrahim, Mikaela Esquivel, Emily E. Van Seventer, Joy X. Jarnagin, Victoria M. Raymond, Carlos U. Corvera, Kenzo Hirose, Eric K. Nakakura, Ryan B. Corcoran, Katherine Van Loon, Chloe E. Atreya
Purpose: Minimal residual disease (MRD) detection identifies patients with colorectal adenocarcinoma (CRC) likely to recur following definitive treatment. We evaluated a plasma only MRD assay to predict recurrence and survival in metastatic CRC patients undergoing curative intent procedures (surgery and/or radiotherapy), with or without (neo)adjuvant chemotherapy. The primary objective of this study
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Targeting the dendritic cell-secreted immunoregulatory cytokine CCL22 alleviates radioresistance Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-01 Jason Bugno, Liangliang Wang, Xianbin Yu, Xuezhi Cao, Jiaai Wang, Xiaona Huang, Kaiting Yang, Andras Piffko, Katherine Chen, Stephen Y. Luo, Emile Naccasha, Yuzhu Hou, Sherry Fu, Chuan He, Yang-Xin Fu, Hua Laura. Liang, Ralph R. Weichselbaum
Purpose: Radiation-mediated immune suppression limits efficacy and is a barrier in cancer therapy. Radiation induces negative regulators of tumor immunity including regulatory T cells (Treg). Mechanisms underlying Treg infiltration after radiotherapy (RT) are poorly defined. Given that dendritic cells (cDC) maintain Treg we sought to identify and target cDC signaling to block Treg infiltration after
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Cervicovaginal metabolome and tumor characteristics for endometrial cancer detection and risk stratification Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-30 Georgia M. Lorentzen, Pawel Laniewski, Haiyan Cui, Nichole D. Mahnert, Jamal Mourad, Matthew P. Borst, Lyndsay Willmott, Dana M. Chase, Denise J. Roe, Melissa M. Herbst-Kralovetz
Purpose: Endometrial cancer is highly prevalent and lacking non-invasive diagnostic techniques. Diagnosis depends on histological investigation of biopsy samples. Serum biomarkers for endometrial cancer have lacked sensitivity and specificity. The objective of this study was to investigate the cervicovaginal environment to improve understanding of metabolic reprogramming related to endometrial cancer
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Toripalimab Plus Bevacizumab as First-line Treatment for Advanced Hepatocellular Carcinoma: A Prospective, Multicenter, Single-Arm, Phase II Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-30 Yajin Chen, Cheng-You Du, Shunli Shen, Wu Zhang, Yunfeng Shan, Ang Lyu, Jianhui Wu, Changzhen Shang, Xuan Luo, Jinxing Wei, Heng Xiao, Jianguo Qiu, Yunpeng Hua, Shutong Wang, Ting Wang, Shengjie Dai, Shuhao Zhang, Bingying Xie, Yinghao Wu, Chunyi Hao
Purpose: This phase II, multicenter, prospective, single-arm study aimed to evaluate the efficacy and safety of toripalimab plus bevacizumab in treating advanced hepatocellular carcinoma (HCC). Patients and methods: Treatment-naïve patients with advanced HCC received toripalimab 240 mg plus bevacizumab 15 mg/kg every 3 weeks. Primary endpoints included safety and tolerability, and objective response
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T cell characteristics impact response and resistance to T cell-redirecting bispecific antibodies in multiple myeloma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-30 Christie P.M. Verkleij, Chloe A. O'Neill, Marloes E.C. Broekmans, Kristine A. Frerichs, Wassilis S.C. Bruins, Carolien Duetz, Sandy Kruyswijk, Serena R. Baglio, Sheri Skerget, Rocio Montes de Oca, Sonja Zweegman, Raluca I. Verona, Tuna Mutis, Niels W.C.J. van de Donk
Purpose: Bispecific antibodies (BsAbs) directed against B-cell maturation antigen (BCMA; teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated MM patients. However, mechanisms underlying primary and acquired resistance remain poorly understood. Experimental design: The anti-MM activity of teclistamab and talquetamab was evaluated
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Clinical and genomic landscape of RAS mutations in gynecologic cancers Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-30 Ji Son, Yingao Zhang, Heather Lin, Oriol Mirallas, Pablo Alvarez Ballesteros, Mirella Nardo, Natalie Clark, R. Tyler Hillman, Erick Campbell, Vijaykumar Holla, Amber M. Johnson, Amadeo B. Biter, Ying Yuan, Lauren P. Cobb, David M. Gershenson, Amir A. Jazaeri, Karen H. Lu, Pamela T. Soliman, Shannon N. Westin, Elizabeth D. Euscher, Barrett C. Lawson, Richard K. Yang, Funda Meric-Bernstam, David S. Hong
Background: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications. Methods: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by Kaplan-Meier method
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A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration-Resistant Prostate Cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-29 Ana M. Aparicio, Rebecca S. S. Tidwell, Shalini S. Yadav, Jiun-Sheng Chen, Miao Zhang, Jingjing Liu, Shuai Guo, Patrick G. Pilie, Yao Yu, Xingzhi Song, Haswanth Vundavilli, Sonali Jindal, Keyi Zhu, Paul V. Viscuse, Justin M. Lebenthal, Andrew W. Hahn, Rama Soundararajan, Paul G. Corn, Amado J. Zurita, Sumit K. Subudhi, Jianhua Zhang, Wenyi Wang, Chad Huff, Patricia Troncoso, James P. Allison, Padmanee
Purpose: To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration-resistant prostate cancers (mCRPC). Experimental design: In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone acetate, prednisone and apalutamide (AAPA; Module 1), then allocated to Modules 2 or 3 based
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Spatial profiling of ovarian carcinoma and tumor microenvironment evolution under neoadjuvant chemotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-26 Elisa Yaniz-Galende, Qinghe Zeng, Juan Francisco Grau-Bejar, Christophe Klein, Félix Blanc-Durand, Audrey Le Formal, Eric Pujade-Lauraine, Laure Chardin, Elodie Edmond, Virginie Marty, Isabelle Ray-Coquard, Florence Joly, Gwenaël Ferron, Patricia Pautier, Dominique Berton-Rigaud, Alain Lortholary, Nadine Dohollou, Christophe Desauw, Michel Fabbro, Emmanuelle Malaurie, Nathalie Bonichon-Lamichhane,
Purpose: Immune tumor microenvironment (iTME) determines ovarian cancer development. This study investigates changes in HLA-I expression, CD8+/Foxp3 ratio, CD8+ cells and coregulators density at diagnosis and upon neoadjuvant chemotherapy (NACT), correlating changes with clinical outcomes. Experimental design: Multiplexed immune profiling and cell clustering analysis was performed on paired matched
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Endometrioid Endometrial RNA Index Predicts Recurrence in Stage I Patients Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-26 Corrine A. Nief, Phoebe M. Hammer, Aihui Wang, Vivek Charu, Amina Tanweer, Babak Litkouhi, Elizabeth Kidd, Andrew J. Gentles, Brooke E. Howitt
Purpose: Risk prediction with genomic and transcriptomic data has the potential to improve patient outcomes by enabling clinicians to identify patients requiring adjuvant treatment approaches, while sparing low-risk patients from unnecessary interventions. Endometrioid endometrial carcinoma (EEC) is the most common cancer in women in developed countries, and rates of endometrial cancer are increasing
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Cell-free human papillomavirus (HPV) DNA is a sensitive biomarker for prognosis and for early detection of relapse in locally advanced cervical cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-26 Lars Sivars, Cecilia Jylhä, Ylva Crona Guterstam, Mark Zupancic, Britta Lindqvist, Magnus Nordenskjöld, Emma Tham, Kristina Hellman
Purpose: Human papillomavirus (HPV) is the cause of the majority of cervical cancers and has been showed to be released as cell-free tumour DNA (ctHPV DNA) into the circulation. We here analyse if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC). Experimental Design: 74 patients with LACC were included
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Sequencing of anti-CD19 therapies in the management of diffuse large B-cell lymphoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-25 Joseph Lownik, Jonathan Boiarsky, Ruemu Birhiray, Akil Merchant, Monica Mead
Several second- and third-line immunotherapeutic options for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplant are directed against the B-cell antigen CD19. The anti-CD19 monoclonal antibody tafasitamab, paired with the immunomodulator lenalidomide, mediates antibody-dependent cellular toxicity and cellular phagocytosis; the antibody–drug
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Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-Oncology Research Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-25 Laura Chambers, Paulina Haight, Julia Chalif, Yogita Mehra, Daniel Spakowicz, Floor J. Backes, Casey M. Cosgrove, David M. O'Malley, Roberto Vargas, Bradley R. Corr, Victoria L. Bae-Jump, Rebecca C. Arend
Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, where immunotherapy is now incorporated in the upfront setting for most patients with advanced endometrial and cervical cancers as the standard of care
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Clinical and Biomarker Analysis of a Phase I/II Study of PDR001 plus Imatinib for Advanced Treatment-refractory Gastrointestinal Stromal Tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-25 Hyung-Don Kim, Min-Hee Ryu, Young Soo Park, Changhoon Yoo, Sung-Joo Kim, Yoon-Koo Kang
Purpose: In this phase Ib/II study, we aimed to evaluate the safety and efficacy of PDR001, an anti-PD-1 antibody, in combination with imatinib in patients with treatment-refractory gastrointestinal stromal tumor (GIST). Patients and Methods: Advanced GIST patients whose disease had progressed on imatinib, sunitinib, and regorafenib were enrolled. In phase Ib, the standard 3+3 dose escalation scheme
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Gene-expression assays to tailor adjuvant endocrine therapy for HR+/HER2- breast cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-24 Michele Bottosso, Federica Miglietta, Grazia Maria. Vernaci, Tommaso Giarratano, Maria Vittoria Dieci, Valentina Guarneri, Gaia Griguolo
Adjuvant endocrine therapy represents the standard of care for almost all HR+/HER2- breast cancers and different agents and durations are currently available. In this context, the tailoring and optimization of adjuvant endocrine treatment by reducing unnecessary toxic treatment while taking into account the biological heterogeneity of HR+/HER2- breast cancer represents a clinical priority. There is
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Fraction dose escalation of hypofractionated radiotherapy with concurrent chemotherapy and subsequent consolidation immunotherapy in locally advanced non-small cell lung cancer: a phase 1 study Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Rui Zhou, FangJie Liu, HongMei Zhang, DaQuan Wang, PengXin Zhang, ShiYang Zheng, YiMei Liu, Li Chen, JinYu Guo, YingYi Zou, Yu-Ming Rong, Hui Liu, Bo Qiu
Purpose: This phase 1 trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Patients and Methods: Split-course hypo-RT and hypo-boost combined with concurrent chemotherapy
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Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Mario E. Lacouture, Elena Goleva, Neil Shah, Veronica Rotemberg, Lukas Kraehenbuehl, Kwami F. Ketosugbo, Taha Merghoub, Tara Maier, Alexander Bang, Stephanie Gu, Trina Salvador, Andrea P. Moy, Taras Lyubchenko, Olivia Xiao, Clifton F. Hall, Evgeny Berdyshev, James Crooks, Ryan Weight, Jeffrey A. Kern, Donald Y.M. Leung
Purpose: Immune-related cutaneous adverse events (ircAEs) occur in ≥50% of patients treated with checkpoint inhibitors (CPI), but mechanisms are poorly understood. Experimental Design: Phenotyping/biomarker analyses were conducted in 200 patients on CPIs (139 with ircAEs, 61 without, control) to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies
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FLT3 agonists and secondary hematopoietic malignancies: a potential class effect Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Henry W. Raeder, Michael W. Drazer
Expansion of cDC cells via FLT3 agonism has promising therapeutic potential in the treatment of advanced solid tumors. Here, we discuss the results of a clinical trial using GS-3583, an FLT3 agonist, that was stopped after a patient in the study developed acute myeloid leukemia.
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Classifying glioma via liquid biopsy--progress towards an unmet clinical need Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Kalil G. Abdullah
The diagnosis and classification of glioma by liquid biopsy represents a critical unmet need in neuro oncology. A recent study demonstrates targeted next generation sequencing (NGS) of cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) as an evolving option for liquid biopsy in patients with glioma.
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A First-in-Human Phase 1 Study of a Tumor-Directed RNA-Interference Drug against HIF2α in Patients with Advanced Clear Cell Renal Cell Carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 James Brugarolas, Gregory Obara, Kathryn E. Beckermann, Brian Rini, Elaine T. Lam, James Hamilton, Thomas Schluep, Min Yi, So Wong, Zhongping Lily Mao, Erick Gamelin, Nizar M. Tannir
Purpose: ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose. Patients and Methods: Subjects with ccRCC and progressive disease
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Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-23 Dickran Kazandjian, Benjamin Diamond, Marios Papadimitriou, Elizabeth Hill, Romanos Sklavenitis-Pistofidis, Bachisio Ziccheddu, Patrick Blaney, Monika Chojnacka, Michael Durante, Kylee Maclachlan, Ryan Young, Saad Usmani, Faith Davies, Gad Getz, Irene Ghobrial, Neha Korde, Gareth Morgan, Francesco Maura, Ola Landgren
PURPOSE: Early intervention for High-Risk Smoldering Multiple Myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered. EXPERIMENTAL DESIGN: Here, we interrogated whole genome and whole exome sequencing for 54 patients across two HR-SMM interventional studies
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A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Ji Won Han, Soon Kyu Lee, Jung Hyun Kwon, Soon Woo Nam, Hyun Yang, Si Hyun Bae, Ji Hoon Kim, Heechul Nam, Chang Wook Kim, Hae Lim Lee, Hee Yeon Kim, Sung Won Lee, Ahlim Lee, U Im Chang, Do Seon Song, Seok-Hwan Kim, Myeong Jun Song, Pil Soo Sung, Jong Young Choi, Seung Kew Yoon, Jeong Won Jang
Background: Given its heterogeneity and diverse clinical outcomes, precise subclassification of BCLC-C hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment. Methods: We recruited 2,626 patients with BCLC-C stage HCC from multiple centers, comprising training/test (n=1,693) and validation cohorts (n=933). The XGBoost was chosen for maximum
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A Cohort Study to Evaluate Genetic Predictors for Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS): Results from ECOG-ACRIN E1Z11 Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Vered Stearns, Opeyemi A. Jegede, Victor Tsu-Shih. Chang, Todd C. Skaar, Jeffrey L. Berenberg, Ranveer Nand, Atif Shafqat, Nisha Lassi. Jacobs, William Luginbuhl, Paul Gilman, Al B. Benson, Judie R. Goodman, Gary L. Buchschacher, N. Lynn. Henry, Charles L. Loprinzi, Patrick J. Flynn, Edith P. Mitchell, Michael Jordan. Fisch, Joseph A. Sparano, Lynne I. Wagner
Purpose: Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS) are common and frequently lead to AI discontinuation. Single nucleotide polymorphisms (SNPs) in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate associations between 10 SNPs and AI discontinuation due to AIMSS. Patients and Methods: Postmenopausal
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Integrating multisector molecular characterization into personalized peptide vaccine design for patients with newly diagnosed glioblastoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-19 Tanner M. Johanns, Elizabeth A.R. Garfinkle, Katherine E. Miller, Alexandra J. Livingstone, Kaleigh F. Roberts, Lakshmi Prakruthi Rao Venkata, Joshua L. Dowling, Michael R. Chicoine, Ralph G. Dacey, Gregory J. Zipfel, Albert H. Kim, Elaine R. Mardis, Gavin P. Dunn
Purpose: Glioblastoma (GBM) patient outcomes remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits
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Low-dose ionizing γ-radiation elicits the extrusion of neutrophil extracellular traps Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Alvaro Teijeira, Saray Garasa, Maria C. Ochoa, Sandra Sanchez-Gregorio, Gabriel Gomis, Carlos Luri-Rey, Rafael Martinez-Monge, Beatrice Pinci, Karmele Valencia, Belen Palencia, Benigno Barbes, Elixabet Bolanos, Arantza Azpilikueta, Marina Garcia-Cardosa, Javier Burguete, Iñaki Eguren-Santamaria, Eneko Garate-Soraluze, Pedro Berraondo, Jose L. Perez-Gracia, Carlos E. de Andrea, Maria E. Rodriguez-Ruiz
Purpose: Cancer patients frequently undergo radiotherapy in their clinical management with unintended irradiation of blood vessels and copiously irrigated organs in which polymorphonuclear leukocytes circulate. Following the observation that such low doses of ionizing radiation are able to induce neutrophils to extrude neutrophil extracellular traps (NETs), we have investigated the mechanisms, consequences
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Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Shifeng Lian, Chenyu Lu, Fugui Li, Xia Yu, Limei Ai, Biao-Hua Wu, Xueyi Gong, Wenjing Zhou, Xuejun Liang, Jiyun Zhan, Yong Yuan, Fang Fang, Zhiwei Liu, Mingfang Ji, Zongli Zheng
Purpose: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. Methods: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited
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Facts and hopes on cancer immunotherapy for small cell lung cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Jon Zugazagoitia, Handerson Osma, Javier Baena, Álvaro C. Ucero, Luis Paz-Ares
Platinum-based chemotherapy plus PD-1 axis blockade is the standard of care in the front-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Despite the robust and consistent increase of long-term survival with PD-1 axis inhibition, the magnitude of the benefit from immunotherapy appears lower as compared to other solid tumors. Several immune evasive mechanisms have been shown to be
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Maintenance pembrolizumab therapy in patients with metastatic HER2-negative breast cancer with prior response to chemotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Toshiaki Iwase, Evan N. Cohen, Hui Gao, Angela Alexander, Megumi Kai, Vivian Chiv, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, Kumiko Kida, Alexandre Reuben, Rachel Layman, David Ramirez, Debu Tripathy, Stacy L. Moulder, Clinton Yam, Vicente Valero, Bora Lim, James M. Reuben, Naoto T. Ueno
Purpose: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer
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Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Melina Peressini, Rosario Garcia-Campelo, Bartomeu Massuti, Cristina Marti, Manuel Cobo, Vanesa Gutiérrez, Manuel Dómine, Jose Fuentes, Margarita Majem, Javier de Castro, Juan Felipe Cordoba, Maria Pilar Diz, Dolores Isla, Emilio Esteban, Enric Carcereny, Laia Vila, Alberto Moreno-Vega, Silverio Ros, Amaia Moreno, Francisco Javier Garcia, Gerardo Huidobro, Carlos Aguado, Victor Cebey-Lopez, Javier
Background: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. Patients and methods: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm
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Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Neeltje Steeghs, Carlos Gomez-Roca, Kristoffer S. Rohrberg, Morten Mau-Sørensen, Debbie Robbrecht, Josep Tabernero, Samreen Ahmed, Maria E. Rodriguez-Ruiz, Caroline Ardeshir, Daniela Schmid, Nassim Sleiman, Carl Watson, Hanna Piper-Lepoutre, David Dejardin, Stefan Evers, Christophe Boetsch, Jehad Charo, Volker Teichgräber, Ignacio Melero
Purpose: Simlukafusp alfa (FAP-IL2v), a tumor-targeted immunocytokine, comprising an interleukin-2 variant moiety with abolished CD25 binding fused to human immunoglobulin G1, is directed against fibroblast activation protein-α. This phase I, open-label, multicenter, dose-escalation and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of
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Efficacy of pembrolizumab and biomarker analysis in patients with WGS-based intermediate to high tumor mutational load: results from the Drug Rediscovery Protocol Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Birgit S. Geurts, Laurien J. Zeverijn, Lindsay V.M. Leek, Jade M. van Berge Henegouwen, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Joris van de Haar, Annemiek van Ommen-Nijhof, Marleen Kok, Paul Roepman, Anne M.L. Jansen, Wendy W.J. de Leng, Maja J. A. de Jonge, Ann Hoeben, Carla M.L. van Herpen, Hans M. Westgeest, Lodewyk F.A. Wessels, Henk M.W. Verheul, Hans Gelderblom, Emile
Purpose: To evaluate efficacy of pembrolizumab across multiple cancer types harboring different levels of Whole-Genome Sequencing (WGS)-based tumor mutational load (TML; total of non-synonymous mutations across the genome) in patients included in the Drug Rediscovery Protocol (NCT02925234). Patients and methods: Patients with solid, treatment-refractory, microsatellite-stable tumors were enrolled in
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Overcoming osimertinib resistance with AKT inhibition in EGFRm-driven Non-Small-Cell-Lung-Cancer with PIK3CA/PTEN alterations Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Ursula Grazini, Aleksandra Markovets, Lucy Ireland, Daniel O'Neill, Benjamin Phillips, Man Xu, Matthias Pfeifer, Tereza Vaclova, Matthew J. Martin, Ludovic Bigot, Luc Friboulet, Ryan Hartmaier, Maria Emanuela Cuomo, Simon T. Barry, Paul D. Smith, Nicolas Floc'h
Purpose: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) indicated for the treatment of EGFR mutated (EGFRm)-driven lung adenocarcinomas. Osimertinib significantly improves progression-free survival in first-line treated patients with EGFRm advanced NSCLC. Despite the durable disease control, the majority of patients receiving osimertinib eventually develop disease
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A cohort study of CNS tumors in Multiple Endocrine Neoplasia Type 1 Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Thomas Graillon, Pauline Romanet, Clara Camilla, Camille Gelin, Romain Appay, Catherine Roche, Arnaud Lagarde, Grégory Mougel, Kaissar Farah, Maëlle Le Bras, Julien Engelhardt, Michel Kalamarides, Matthieu Peyre, Aymeric Amelot, Evelyne Emery, Elsa Magro, Helene Cebula, Rabih Aboukais, Catherine Bauters, Emmanuel Jouanneau, Moncef Berhouma, Thomas Cuny, Henry Dufour, Hugues Loiseau, Dominique Figarella-Branger
Purpose: Multiple Endocrine Neoplasia Type-1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Hereby, we aimed to describe the frequency, the incidence and specific clinical and histological features of CNS tumors in the MEN1 population (except pituitary tumors). Experimental design: The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990
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Diffuse pleural mesotheliomas with genomic near-haploidization: a newly recognized subset with distinct clinical, histologic, and molecular features Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-17 Soo-Ryum Yang, Gowtham Jayakumaran, Jamal Benhamida, Christopher A. Febres Aldana, Rachel Fanaroff, Jason Chang, Erika Gedvilaite, Liliana B. Villafania, Jennifer L. Sauter, Michael Offin, Marjorie G. Zauderer, Marc Ladanyi
Purpose: Diffuse pleural mesotheliomas (DPMs) with genomic near-haploidization (GNH) represent a novel subtype first recognized by the TCGA project; however, its clinicopathologic and molecular features remain poorly defined. Experimental design: We analyzed clinical genomic profiling data from 290 patients with DPM using the MSK-IMPACT assay. Allele-specific copy number analysis was performed using
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Mutation Patterns Predict Drug Sensitivity in Acute Myeloid Leukemia Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-15 Guangrong Qin, Jin Dai, Sylvia Chien, Timothy J. Martins, Brenda Loera, Quy H. Nguyen, Melanie L. Oakes, Bahar Tercan, Boris Aguilar, Lauren Hagen, Jeannine McCune, Richard Gelinas, Raymond J. Monnat, Ilya Shmulevich, Pamela S. Becker
Purpose: The inherent genetic heterogeneity of acute myeloid leukemia (AML) has challenged the development of precise and effective therapies. The objective of this study was to elucidate the genomic basis of drug resistance or sensitivity, identify signatures for drug response prediction, and provide resources to the research community. Experimental Design: We performed targeted sequencing, high-throughput
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A Real-world Toxicity Atlas Shows that Adverse Events of Combination Therapies Commonly Result in Additive Interactions Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-10 Asli Küçükosmanoglu, Silvia Scoarta, Megan Houweling, Nicoleta Spinu, Thomas Wijnands, Niek Geerdink, Carolien Meskers, Georgi K. Kanev, Bert Kiewiet, Mathilde Kouwenhoven, David Noske, Tom Wurdinger, Marianne Pouwer, Mark Wolff, Bart A. Westerman
Purpose: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting. Experimental Design: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized
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Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Lena Fischer-Riepe, Sareetha Kailayangiri, Katharina Zimmermann, Rita Pfeifer, Michael Aigner, Bianca Altvater, Sascha Kretschmann, Simon Völkl, Jordan Hartley, Celine Dreger, Katja Petry, Andreas Bosio, Angelika von Döllen, Wolfgang Hartmann, Holger Lode, Dennis Görlich, Andreas Mackensen, Melanie Jungblut, Axel Schambach, Hinrich Abken, Claudia Rossig
Purpose: Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR T cells) is a promising principle to overcome the limited activity of canonical CAR T cells against solid cancers. Experimental Design: We developed an investigational medicinal product, GD2IL18CART, consisting of CAR T cells directed against ganglioside GD2 with CAR-inducible IL18 to enhance their activation response
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Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Hyung-Joo Oh, Suk-Chul Bae, In-Jae Oh, Cheol-Kyu Park, Kyoung-Mi Jung, Da-Mi Kim, Jung-Won Lee, Chang Kyun Kang, Il Yeong Park, Young-Chul Kim
Purpose: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR–tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer
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Preclinical efficacy of a PSMA-targeted actinium-225 conjugate (225Ac-macropa-pelgifatamab) - a targeted alpha therapy for prostate cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Christoph A. Schatz, Sabine Zitzmann-Kolbe, Ingrid Moen, Monika Klotz, Shankari Nair, Stefan Stargard, Roger M. Bjerke, Katrine Wickstrøm Biseth, Yuan Zeng. Feng, Bård Indrevoll, Véronique Cruciani, Jenny Karlsson, Bernard Haendler, Carsten H. Nielsen, Maria Z. Alfsen, Stefanie Hammer, Hartwig Hennekes, Alan Cuthbertson, Urs B. Hagemann, Aasmund Larsen
Purpose: Initially, prostate cancer responds to hormone therapy but eventually resistance develops. Beta emitter-based PSMA (prostate-specific membrane antigen)-targeted radionuclide therapy is approved for the treatment of metastatic castration-resistant prostate cancer. Here we introduce a targeted alpha therapy (TAT) consisting of the PSMA antibody pelgifatamab covalently linked to a macropa chelator
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CB307: A Dual Targeting Costimulatory Humabody VH Therapeutic for Treating PSMA-Positive Tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Sophie Archer, Phillip M. Brailey, Minjung Song, Phillip D. Bartlett, Ines Figueiredo, Bora Gurel, Christina Guo, Verena Brucklacher-Waldert, H. Lorraine Thompson, Jude Akinwale, Samantha E. Boyle, Christine Rossant, Neil R. Birkett, Julia Pizzey, Mark Maginn, James Legg, Richard Williams, Colette M. Johnston, Philip Bland-Ward, Johann S. de Bono, Andrew J. Pierce
Purpose: CD137 is a T- and NK-cell costimulatory receptor involved in consolidating immunologic responses. The potent CD137 agonist urelumab has shown clinical promise as a cancer immunotherapeutic but development has been hampered by on-target off-tumor toxicities. A CD137 agonist targeted to the prostate-specific membrane antigen (PSMA), frequently and highly expressed on castration-resistant metastatic
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Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147) Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Sangini S. Sheth, Ji Eun Oh, Stefania Bellone, Eric R. Siegel, Michelle Greenman, Levent Mutlu, Blair McNamara, Shefali Pathy, Mitchell Clark, Masoud Azodi, Gary Altwerger, Vaagn Andikyan, Gloria Huang, Elena Ratner, Daniel J. Kim, Akiko Iwasaki, Angelique W. Levi, Natalia Buza, Pei Hui, Sean Flaherty, Peter E. Schwartz, Alessandro D. Santin
Purpose: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. Patients and Methods: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with
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Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-09 Farah Ballout, Heng Lu, Nadeem Bhat, Lei Chen, Dunfa Peng, Zheng Chen, Steven Chen, Xiaodian Sun, Silvia Giordano, Simona Corso, Alexander Zaika, Oliver McDonald, Alan S. Livingstone, Wael El-Rifai
Purpose: TGFβ signaling is implicated in the progression of most cancers, including esophageal adenocarcinoma (EAC). Emerging evidence indicates that TGFβ signaling is a key factor in the development of resistance toward cancer therapy. Experimental Design: In this study, we developed patient-derived organoids and patient-derived xenograft models of EAC and performed bioinformatics analysis combined
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Impact of Circulating Tumor Cell–Expressed Prostate-Specific Membrane Antigen and Prostate-Specific Antigen Transcripts in Different Stages of Prostate Cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-08 Hyungseok Cho, Seok-Soo Byun, Nak-Hoon Son, Jae Il Chung, Won Ik Seo, Chan Ho Lee, Todd M. Morgan, Ki-Ho Han, Jae-Seung Chung
Purpose: Prostate-specific membrane antigen (PSMA)–based images, which visually quantify PSMA expression, are used to determine prostate cancer micrometastases. This study evaluated whether a circulating tumor cell (CTC)–based transcript platform, including PSMA mRNA, could help identify potential prognostic markers in prostate cancer. Experimental Design: We prospectively enrolled 21 healthy individuals
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Stabilizing tumor resident mast cells restores T cell infiltration and sensitizes sarcomas to PD-L1 inhibition Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 Myrofora Panagi, Fotios Mpekris, Chrysovalantis Voutouri, Andreas G. Hadjigeorgiou, Chloe Symeonidou, Eleni Porfyriou, Christina Michael, Andreas Stylianou, John D. Martin, Horacio Cabral, Anastasia Constantinidou, Triantafyllos Stylianopoulos
Purpose: To explore the cellular crosstalk of tumor resident mast cells (MCs) in controlling the activity of cancer-associated fibroblasts (CAFs) to overcome TME abnormalities, enhancing the efficacy of immune checkpoint inhibitors (ICIs) in sarcoma. Experimental Design: We used a coculture system followed by further validation in mouse models of fibrosarcoma and osteosarcoma with or without administration
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IRX4204 Induces Senescence and Cell Death in HER2-positive Breast Cancer and Synergizes with Anti-HER2 Therapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 Cassandra L. Moyer, Amanda Lanier, Jing Qian, Darian Coleman, Jamal Hill, Vidyasagar Vuligonda, Martin E. Sanders, Abhijit Mazumdar, Powel H. Brown
Purpose: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well-tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response
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Safety and preliminary efficacy of pembrolizumab following trans-arterial chemoembolization for hepatocellular carcinoma: the PETAL phase Ib study. Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 David J. Pinato, Antonio D'Alessio, Claudia Angela Maria. Fulgenzi, Alexandra Emilia Schlaak, Ciro Celsa, Saskia Killmer, Jesus Miguens. Blanco, Caroline Ward, Charalampos-Vlasios Stikas, Mark R. Openshaw, Nicole Acuti, Georgios Nteliopoulos, Cristina Balcells, Hector C. Keun, Robert D. Goldin, Paul J. Ross, Alessio Cortellini, Robert Thomas, Anna Mary. Young, Nathan Danckert, Paul Tait, Julian R.
Background. TACE may prime adaptive immunity and enhance immunotherapy efficacy. PETAL evaluated safety, preliminary activity of TACE plus pembrolizumab and explored mechanisms of efficacy. Methods. Patients with liver-confined HCC were planned to receive up to 2 rounds of TACE followed by pembrolizumab 200 mg every 21 days commencing 30-days post-TACE until disease progression or unacceptable toxicity
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New means and challenges in the targeting of BTK Clin. Cancer Res. (IF 11.5) Pub Date : 2024-04-05 Vindhya Nawaratne, Anya K. Sondhi, Omar Abdel-Wahab, Justin Taylor
Bruton’s tyrosine kinase (BTK) is central to the survival of malignant and normal B-lymphocytes and has been a crucial therapeutic target of several generations of kinase inhibitors and newly developed degraders. These new means for targeting BTK have added additional agents to the armamentarium for battling cancers dependent on B-cell receptor (BCR) signaling, including chronic lymphocytic leukemia