journal
https://read.qxmd.com/read/36988617/can-molecular-imaging-find-a-path-to-navigate-evolving-breast-cancer-treatments
#1
JOURNAL ARTICLE
Hannah M Linden, David A Mankoff
FES PET is an FDA-approved imaging biomarker. Like IHC, FES positivity predicts clinical benefit of endocrine therapy. In addition, FES measures the target activity in endocrine agent drug development. A recent study found that whole body tumor heterogeneity of expression predicts clinical benefit, and serial FES monitors ER blockade and post treatment release.
March 29, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36988276/immunologic-predictors-for-clinical-responses-during-immune-checkpoint-blockade-in-patients-with-myelodysplastic-syndromes
#2
JOURNAL ARTICLE
Sung-Eun Lee, Feng Wang, Maison Grefe, Abel Trujillo-Ocampo, Wilfredo Ruiz-Vasquez, Koichi Takahashi, Hussein A Abbas, Pamella Borges, Dinler Amaral Antunes, Gheath Al-Atrash, Naval Daver, Jeffrey J Molldrem, Andrew Futreal, Guillermo Garcia-Manero, Jin S Im
PURPOSE: The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA). EXPERIMENTAL DESIGN: Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment...
March 29, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36976261/co-clinical-study-of-fam-trastuzumab-deruxtecan-ds8201a-in-patient-derived-xenograft-models-of-uterine-carcinosarcoma-and-its-association-with-clinical-efficacy
#3
JOURNAL ARTICLE
Shigehiro Yagishita, Tadaaki Nishikawa, Hiroshi Yoshida, Daisuke Shintani, Sho Sato, Maiko Miwa, Mikiko Suzuki, Masanori Yasuda, Yusuke Ogitani, Takahiro Jikoh, Kan Yonemori, Kosei Hasegawa, Akinobu Hamada
BACKGROUND: Uterine carcinosarcoma (UCS), a subtype of endometrial carcinoma, is a rare and aggressive cancer with a poor prognosis. High clinical efficacy of trastuzumab deruxtecan (T-DXd) in HER2-expressing UCS was recently reported in phase 2 trial (STATICE trial). We performed a co-clinical study of T-DXd using patient-derived xenograft (PDX) models of participants in the STATICE trial. PATIENTS AND METHODS: Tumor specimens were resected during primary surgery or biopsied at recurrence from patients with UCS and transplanted into immunodeficient mice...
March 28, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36976253/breaking-up-isn-t-hard-to-do-isolating-cell-free-dna-fragments-in-osteosarcoma
#4
JOURNAL ARTICLE
Daniel A Weiser, Masanori Hayashi, Mark A Applebaum
The novel use of blood-based biospecimens from a retrospective cohort of 50 patients with osteosarcoma was recently studied. The potential clinical utility of sorting cell-free DNA by fragment size was defined, with shorter tumor-specific DNA enrichment providing prognostic value and allowing for streamlined molecular profiling of circulating tumor material.
March 28, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36976175/a-multipronged-unbiased-strategy-guides-the-development-of-an-anti-egfr-epha2-bispecific-antibody-for-combination-cancer-therapy
#5
JOURNAL ARTICLE
Amr El Zawily, Frederick S Vizeacoumar, Renuka Dahiya, Sara L Banerjee, Kalpana K Bhanumathy, Hussain Elhasasna, Glinton Hanover, Jessica C Sharpe, Malkon G Sanchez, Paul Greidanus, R Greg Stacey, Kyung-Mee Moon, Ilya Alexandrov, Juha P Himanen, Dimitar B Nikolov, Humphrey Fonge, Aaron P White, Leonard J Foster, Bingcheng Wang, Behzad M Toosi, Nicolas Bisson, Tajib A Mirzabekov, Franco J Vizeacoumar, Andrew Freywald
PURPOSE: Accumulating analyses of pro-oncogenic molecular mechanisms triggered a rapid development of targeted cancer therapies. Although many of these treatments produce impressive initial responses, eventual resistance onset is practically unavoidable. One of the main approaches for preventing this refractory condition relies on the implementation of combination therapies. This includes dual-specificity reagents that affect both of their targets with a high level of selectivity. Unfortunately, selection of target combinations for these treatments is often confounded by limitations in our understanding of tumor biology...
March 28, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36971786/myosin-light-chain-kinase-inhibition-potentiates-the-anti-tumor-effects-of-avapritinib-in-pdgfra-d842v-mutant-gastrointestinal-stromal-tumor
#6
JOURNAL ARTICLE
Ferdinand Rossi, Mengyuan Liu, Andrew Tieniber, Mark S Etherington, Andrew Hanna, Gerardo A Vitiello, Nesteene J Param, Kevin Do, Laura Wang, Cristina R Antonescu, Shan Zeng, Jennifer Q Zhang, Ronald P DeMatteo
PURPOSE: To create an in vivo model of PDGFRA D842V-mutant gastrointestinal stromal tumor (GIST) and identify the mechanism of tumor persistence following avapritinib therapy. EXPERIMENTAL DESIGN: We created a patient-derived xenograft of PDGFRA D842V-mutant GIST and tested the effects of imatinib, avapritinib, and ML-7, an inhibitor of myosin light chain kinase (MYLK). Bulk tumor RNA sequencing and oncogenic signaling were evaluated. Apoptosis, survival, and actin cytoskeleton were evaluated in GIST T1 cells and isolated PDX cells in vitro...
March 27, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36971777/randomized-trial-of-tepotinib-plus-gefitinib-versus-chemotherapy-in-egfr-mutant-nsclc-with-egfr-inhibitor-resistance-due-to-met-amplification-insight-final-analysis
#7
JOURNAL ARTICLE
Chong Kin Liam, Azura Rozila Ahmad, Te-Chun Hsia, Jianying Zhou, Dong-Wan Kim, Ross Andrew Soo, Ying Cheng, Shun Lu, Sang Won Shin, James Chi-Hsin Yang, Yiping Zhang, Jun Zhao, Karin Berghoff, Rolf Bruns, Andreas Johne, Yi-Long Wu
PURPOSE: The final analyses of the INSIGHT phase II study evaluating tepotinib (a selective MET inhibitor) plus gefitinib versus chemotherapy in patients with MET-altered EGFR-mutant NSCLC (data cut-off: September 3, 2021). PATIENTS AND METHODS: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy...
March 27, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36971773/a-phase-2-study-of-epacadostat-and-pembrolizumab-in-patients-with-advanced-sarcoma
#8
JOURNAL ARTICLE
Ciara M Kelly, Li-Xuan Qin, Karissa A Whiting, Allison L Richards, Viswatej Avutu, Jason E Chan, Ping Chi, Mark A Dickson, Mrinal M Gounder, Mary Louise Keohan, Sujana Movva, Benjamin A Nacev, Evan Rosenbaum, Travis Adamson, Samuel Singer, Edmund K Bartlett, Aimee M Crago, Sam S Yoon, Sinchun Hwang, Joseph P Erinjeri, Cristina R Antonescu, William D Tap, Sandra P D'Angelo
PURPOSE: Epacadostat, an indole 2,3 dioxygenase 1 (IDO1) inhibitor proposed to shift the tumor microenvironment toward an immune-stimulated state, showed early promise in melanoma but has not been studied in sarcoma. This study combined epacadostat with pembrolizumab, which has modest activity in select sarcoma subtypes. EXPERIMENTAL DESIGN: This phase 2 study enrolled patients with advanced sarcoma into five cohorts including i) undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma, ii) liposarcoma (LPS), iii) leiomyosarcoma (LMS), iv) vascular sarcoma, including angiosarcoma and epithelioid hemangioendothelioma (EHE), and v) other subtypes...
March 27, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36951687/a-tumor-suppressive-molecular-axis-ep300-circrere-mir-6837-3p-mavs-activates-type-i-interferon-pathway-and-anti-tumor-immunity-to-suppress-colorectal-cancer
#9
JOURNAL ARTICLE
Nan Ding, A-Bin You, Hu Yang, Guo-Sheng Hu, Chun-Ping Lai, Wen Liu, Feng Ye
PURPOSE: The oncogenic role of circRNAs has been well-studied in cancers including colorectal cancer (CRC). However, tumor-suppressive circRNAs and the mechanism through which they exert their anti-tumor effects remain largely unknown. We aim to find out the critical tumor-suppressive circRNAs and their possibility to serve as gene therapy targets. EXPERIMENTAL DESIGN: CircRNA sequencing, gain- and loss- of function experiments,and transcriptomic analysis were performed to find tumor-suppressive and anti-tumor immunity effects of circRERE...
March 23, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36951682/granulocyte-colony-stimulating-factor-is-a-novel-mediator-of-t-cell-suppression-and-an-immunotherapeutic-target-for-women-with-colon-cancer
#10
JOURNAL ARTICLE
Anita L Ray, Apryl S Saunders, Robert A Nofchissey, Megan A Reidy, Maria Kamal, Megan R Lerner, Kar-Ming Fung, Mark L Lang, Joshua A Hanson, Shaoxuan Guo, Maria G Urdaneta-Perez, Samara E Lewis, Michael Cloyde, Katherine T Morris
PURPOSE: Granulocyte colony stimulating factor (GCSF) enhances colon cancer development. This study defines the prevalence and effects of increased GCSF signaling in human colon cancers and investigates GCSF inhibition as an immunotherapeutic strategy against metastatic colon cancer. EXPERIMENTAL DESIGN: Patient samples were used to evaluate GCSF and GCSF receptor (GCSFR) levels by immunohistochemistry with sera used to measure GCSF levels. PBMCs were used to assess the rate of GCSFR+ T cells and interferon γ (IFNγ) responses to chronic ex vivo GCSF...
March 23, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36951523/fda-approval-summary-atezolizumab-as-adjuvant-treatment-following-surgical-resection-and-platinum-based-chemotherapy-for-stage-ii-to-iiia-nsclc
#11
JOURNAL ARTICLE
Luckson N Mathieu, Erin Larkins, Arup K Sinha, Pallavi S Mishra-Kalyani, Samina Jafri, Shyam Kalavar, Soma Ghosh, Kirsten B Goldberg, Richard Pazdur, Julia A Beaver, Harpreet Singh
On October 15, 2021, the U.S. Food and Drug Administration (FDA) approved atezolizumab as adjuvant therapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have programmed death-ligand 1 (PD-L1) expression on ≥ 1% of tumor cells (TC), as detected by an FDA-approved test. The approval was based on results from the IMpower010 trial, in which 1005 patients with NSCLC who had completed tumor resection and cisplatin-based adjuvant chemotherapy were randomized 1:1 to receive atezolizumab for 16 cycles or best supportive care (BSC)...
March 23, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36939557/accessible-data-collections-for-improved-decision-making-in-neuro-oncology-clinical-trials
#12
JOURNAL ARTICLE
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 since 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, is the difficulty in accessing high-quality patient-level data. Academic research groups generally do not have access to suitable datasets to effectively leverage external data for planning and analyses of new clinical trials...
March 20, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36939530/expression-and-therapeutic-targeting-of-trop-2-in-treatment-resistant-prostate-cancer
#13
JOURNAL ARTICLE
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 (ADCs). EXPERIMENTAL DESIGN: Trop-2 gene (TACSTD2) expression and markers of treatment resistance from prostate biopsies were analyzed using data from four previously curated cohorts of mCRPC (n = 634) and the PROMOTE study (dbGaP accession phs001141...
March 20, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36928921/a-phase-ii-trial-of-guadecitabine-plus-atezolizumab-in-metastatic-urothelial-carcinoma-progressing-after-initial-immune-checkpoint-inhibitor-therapy
#14
JOURNAL ARTICLE
H Josh Jang, Galen Hostetter, Alexander W MacFarlane, Zachary Madaj, Eric A Ross, Toshinori Hinoue, Justin R Kulchycki, Ryan S Burgos, Mahvish Tafseer, R Katherine Alpaugh, Candice L Schwebel, Rutika Kokate, Daniel M Geynisman, Matthew R Zibelman, Pooja Ghatalia, Peter W Nichols, Woonbok Chung, Jozef Madzo, Noah M Hahn, David I Quinn, Jean-Pierre J Issa, Michael J Topper, Stephen B Baylin, Hui Shen, Kerry S Campbell, Peter A Jones, Elizabeth R Plimack
PURPOSE: Based on preclinical evidence of epigenetic contribution to sensitivity and resistance to immune checkpoint inhibitors (ICI), we hypothesized that guadecitabine (hypomethylating agent) and atezolizumab (anti-PD-L1) together would potentiate a clinical response in patients with metastatic urothelial carcinoma (UC) unresponsive to initial immune checkpoint blockade therapy. PATIENTS AND METHODS: We designed a single arm Phase II study (NCT03179943) with a safety run-in to identify the recommended phase II dose of the combination therapy of guadecitabine and atezolizumab...
March 16, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36920243/the-enduring-effects-of-covid-for-cancer-care-learning-from-real-life-clinical-practice
#15
JOURNAL ARTICLE
Alex Broom, Leah Williams Veazey, Katherine Kenny, Imogen Harper, Michelle Peterie, Alexander Page, Nicole Cort, Jennifer Durling, Eric S Lipp, Aaron C Tan, Kyle M Walsh, Brent A Hanks, Margaret Johnson, Amanda van Swearingen, Carey K Anders, David M Ashley, Mustafa Khasraw
For three years, COVID-19 has circulated among our communities and around the world, fundamentally changing social interactions, health care systems, and service delivery. For people living with (and receiving treatment for) cancer, pandemic conditions presented significant additional hurdles in an already unstable and shifting environment, including disrupted personal contact with care providers, interrupted access to clinical trials, distanced therapeutic encounters, multiple immune vulnerabilities, and new forms of financial precarity...
March 15, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36917693/treatment-of-prostate-cancer-with-cd46-targeted-225ac-alpha-particle-radioimmunotherapy
#16
JOURNAL ARTICLE
Anil P Bidkar, Sinan Wang, Kondapa Naidu Bobba, Emily Chan, Scott Bidlingmaier, Emily A Egusa, Robin Peter, Umama Ali, Niranjan Meher, Anju Wadhwa, Suchi Dhrona, Chandrashekhar Dasari, Denis Beckford-Vera, Yang Su, Ryan Tang, Li Zhang, Jiang He, David M Wilson, Rahul Aggarwal, Henry F VanBrocklin, Youngho Seo, Jonathan Chou, Bin Liu, Robert R Flavell
PURPOSE: Radiopharmaceutical therapy is changing the standard of care in prostate cancer (PCa) and other malignancies. We previously reported high CD46 expression in PCa and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. EXPERIMENTAL DESIGN: [225Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell derived (22Rv1, DU145), and patient derived (LTL-545, LTL484) PCa xenograft models...
March 14, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36917691/randomized-phase-2-cabazitaxel-dose-individualization-and-neutropenia-prevention-trial-cainta-in-patients-with-metastatic-castration-resistant-prostate-cancer
#17
JOURNAL ARTICLE
Aurelius Omlin, Richard Cathomas, Gunhild von Amsberg, Christoph Reuter, Susan Feyerabend, Wolfgang Loidl, Martin Boegemann, Anja Lorch, Axel Heidenreich, Igor Tsaur, Julian Larcher-Senn, Stefan Buck, Ron H J Mathijssen, Ulrich Jaehde, Silke Gillessen, Markus Joerger
PURPOSE: There is ongoing controversy about the recommended dose of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). EXPERIMENTAL DESIGN: This multicenter phase II open-label, randomized, parallel-group study compared 3-weekly cabazitaxel at 25 mg/m2 (conventional Arm A) with cabazitaxel therapeutic drug monitoring (TDM) (experimental Arm B) in mCRPC. The primary objective was to improve the clinical feasibility rate (CFR) defined as the absence of grade 4 neutropenia or thrombocytopenia, any thrombocytopenia with bleeding, febrile neutropenia, severe non-hematological toxicity, withdrawal for cabazitaxel-related toxicity or death...
March 14, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36913537/efficacy-of-osimertinib-in-patients-with-lung-cancer-positive-for-uncommon-egfr-exon-19-deletion-mutations
#18
JOURNAL ARTICLE
Michael J Grant, Jacqueline V Aredo, Jacqueline H Starrett, Paul Stockhammer, Iris K van Alderwerelt van Rosenburgh, Anna Wurtz, Andrew J Piper-Valillo, Zofia Piotrowska, Christina Falcon, Helena A Yu, Charu Aggarwal, Dylan Scholes, Tejas Patil, Christina Nguyen, Manali Phadke, Fang-Yong Li, Joel Neal, Mark A Lemmon, Zenta Walther, Katerina Politi, Sarah B Goldberg
PURPOSE: The uncommon EGFR exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared to the common ex19del, E746_A750del in preclinical models. The clinical efficacy of osimertinib in patients with non-small cell lung cancer (NSCLC) harboring L747_A750>P and other uncommon ex19dels is not known. DESIGN: The AACR GENIE database was interrogated to characterize the frequency of individual ex19dels relative to other variants, and a multi-center retrospective cohort was used to compare clinical outcomes for patients with tumors harboring E746_A750del, L747_A750>P, and other uncommon ex19dels who received osimertinib in the first line (1L) or in second or later lines of therapy and were T790M+ (≥2L)...
March 13, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36897758/psma-positive-circulating-tumor-cell-detection-and-outcomes-with-abiraterone-or-enzalutamide-treatment-in-men-with-metastatic-castrate-resistant-prostate-cancer
#19
JOURNAL ARTICLE
Santosh Gupta, Susan Halabi, Qian Yang, Akash Roy, Alisa Tubbs, Yamini Gore, Daniel J George, David M Nanus, Emmanuel S Antonarakis, Daniel C Danila, Russell Z Szmulewitz, Richard Wenstrup, Andrew J Armstrong
BACKGROUND: In men with mCRPC, PSMA-targeted radioligand therapy has drastically improved clinical outcomes. A liquid biopsy characterizing PSMA expression could be useful in guiding optimal therapy. METHODS: We conducted a retrospective analysis of the prospective multicenter PROPHECY trial of men with mCRPC (n=118) treated with abiraterone (abi) or enzalutamide (enza). CTCs were enriched (CTC/mL) and characterized for PSMA protein expression/heterogeneity at baseline and progression...
March 10, 2023: Clinical Cancer Research
https://read.qxmd.com/read/36892582/the-oncolytic-adenovirus-xvir-n-31-joins-forces-with-cdk4-6-inhibition-augmenting-innate-and-adaptive-antitumor-immunity-in-ewing-sarcoma
#20
JOURNAL ARTICLE
Sebastian Johannes Schober, Caroline Schoening, Jennifer Eck, Charlotte Middendorf, Julia Lutsch, Pia Knoch, Anna Josefine von Ofen, Hendrik Gassmann, Melanie Thiede, Julia Hauer, Andreas Kolk, Klaus Mantwill, Juergen E Gschwend, Stefan E G Burdach, Roman Nawroth, Uwe Thiel, Per Sonne Holm
PURPOSE: Ewing sarcoma (EwS) is a highly malignant pediatric tumor characterized by a non-T cell-inflamed immune-evasive phenotype. When relapsed or metastasized, survival is poor, emphasizing the need for novel treatment strategies. Here, we analyze the novel combination approach using the YB-1-driven oncolytic adenovirus XVir-N-31 and CDK4/6 inhibition to augment EwS immunogenicity. EXPERIMENTAL DESIGN: In vitro, viral toxicity, replication, and immunogenicity were studied in several EwS cell lines...
March 9, 2023: Clinical Cancer Research
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