journal
https://read.qxmd.com/read/38597991/a-real-world-toxicity-atlas-shows-that-adverse-events-of-combination-therapies-commonly-result-in-additive-interactions
#1
JOURNAL ARTICLE
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 as heat maps onto a two-dimensional grid. Adverse event frequencies were shown as colors to assess the ratio between individual and combined drug effects...
April 10, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38593249/nicotinamide-in-combination-with-egfr-tkis-for-the-treatment-of-stage-iv-lung-adenocarcinoma-with-egfr-mutations-a-randomized-double-blind-phase-iib-trial
#2
JOURNAL ARTICLE
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 carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth...
April 9, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38593230/preclinical-development-of-car-t-cells-with-antigen-inducible-il18-enforcement-to-treat-gd2-positive-solid-cancers
#3
JOURNAL ARTICLE
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 and cytolytic effector functions in the tumor microenvironment...
April 9, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38593226/cb307-a-dual-targeting-costimulatory-humabody-vh-therapeutic-for-treating-psma-positive-tumors
#4
JOURNAL ARTICLE
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 prostate cancer (mCRPC) tumor cells, could bring effective immunotherapy to this immunologically challenging to address disease...
April 9, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38593212/preclinical-efficacy-of-a-psma-targeted-actinium-225-conjugate-225ac-macropa-pelgifatamab-a-targeted-alpha-therapy-for-prostate-cancer
#5
JOURNAL ARTICLE
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 and labeled with actinium-225 and compare its efficacy and tolerability with other TATs...
April 9, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38592381/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
#6
JOURNAL ARTICLE
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 self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A)...
April 9, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38592373/targeting-smad3-improves-response-to-oxaliplatin-in-esophageal-adenocarcinoma-models-by-impeding-dna-repair
#7
JOURNAL ARTICLE
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 with functional genetics to investigate the role of SMAD family member 3 (SMAD3) in EAC resistance to oxaliplatin...
April 9, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38587547/impact-of-circulating-tumor-cell-expressed-prostate-specific-membrane-antigen-and-prostate-specific-antigen-transcripts-in-different-stages-of-prostate-cancer
#8
JOURNAL ARTICLE
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 and 247 patients with prostate cancer [localized prostate cancer (LPCa), n = 94; metastatic hormone-sensitive prostate cancer (mHSPC), n = 44; and metastatic castration-resistant prostate cancer (mCRPC), n = 109]...
April 8, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38578683/co-occurring-egfr-p-e709x-mutation-mediates-primary-resistance-to-the-third-generation-egfr-tkis-in-egfr-p-g719x-mutant-patients-with-advanced-nsclc
#9
JOURNAL ARTICLE
Lanlan Pang, Yihua Huang, Weitao Zhuang, Yaxiong Zhang, Jun Liao, Yue Hao, Feng Hao, Guoqian Wang, Ze-Xin Chase Chen, Yu Zhu, Mengzhen Li, Zhengbo Song, Bo Peng Deng, Jing Li, Li Zhang, Wenfeng Fang
PURPOSE: Current NCCN guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X mutant patients, it is unclear which regimen is the preferred treatment option. EXPERIMENTAL DESIGN: A large cohort of 4228 treatment-naïve patients with lung cancer who underwent targeted NGS testing was screened for EGFR p...
April 5, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38578610/safety-and-preliminary-efficacy-of-pembrolizumab-following-trans-arterial-chemoembolization-for-hepatocellular-carcinoma-the-petal-phase-ib-study
#10
JOURNAL ARTICLE
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 Marchesi, Bertram Bengsch, Rohini Sharma
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 for up to 1 year. Primary endpoint was safety, 21-days dose-limiting toxicities (DLT) from pembrolizumab initiation...
April 5, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38578606/new-means-and-challenges-in-the-targeting-of-btk
#11
JOURNAL ARTICLE
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 and other non-Hodgkin lymphomas. However, the development of acquired resistance mutations to each of these classes of BTK inhibitors has led to new challenges in targeting BTK as well as novel insights into BCR signaling...
April 5, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38578281/stabilizing-tumor-resident-mast-cells-restores-t-cell-infiltration-and-sensitizes-sarcomas-to-pd-l1-inhibition
#12
JOURNAL ARTICLE
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 of the MC stabilizer and antihistamine ketotifen. To evaluate the contribution of ketotifen in sensitizing tumors to therapy, we performed combination studies with doxorubicin chemotherapy and anti-PD-L1 (B7-H1, clone 10F...
April 5, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38578278/irx4204-induces-senescence-and-cell-death-in-her2-positive-breast-cancer-and-synergizes-with-anti-her2-therapy
#13
JOURNAL ARTICLE
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 and potential mechanism of action. EXPERIMENTAL DESIGN: IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models and primary PDX tumors...
April 5, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38573708/statins-do-not-significantly-affect-oxidative-nitrosative-stress-biomarkers-in-the-prevent-randomized-clinical-trial
#14
JOURNAL ARTICLE
Igor Makhlin, Biniyam G Demissei, Ralph D'Agostino, W Greg Hundley, Camelia Baleanu-Gogonea, Nicholas S Wilcox, Anna Chen, Amanda M Smith, Nathaniel Sean O'Connell, James Januzzi, Glenn J Lesser, Marielle Scherrer-Crosbie, Borja Ibáñez, W H Wilson Tang, Bonnie Ky
PURPOSE: Preventing Anthracycline Cardiovascular Toxicity with Statins (PREVENT) (NCT01988571) randomized breast cancer or lymphoma patients receiving anthracyclines to atorvastatin 40 mg daily or placebo. We evaluated the effects of atorvastatin on oxidative and nitrosative stress biomarkers, and explored whether these biomarkers could explain the lack of effect of atorvastatin on LVEF in PREVENT. PATIENTS AND METHODS: Blood samples were collected and cardiac magnetic resonance imaging was performed prior to doxorubicin initiation and at 6 and 24 months...
April 4, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38573684/comprehensive-genomic-profiling-alters-clinical-diagnoses-in-a-significant-fraction-of-tumors-suspicious-of-sarcoma
#15
JOURNAL ARTICLE
Ingegerd Öfverholm, Karin Wallander, Cecilia Haglund, Venkatesh Chellappa, Johan Wejde, Anna Gellerbring, Valtteri Wirta, Annick Renevey, Eva Caceres, Panagiotis Tsagkozis, Markus Mayrhofer, Andri Papakonstantinou, Christina Linder-Stragliotto, Robert Bränström, Olle Larsson, Johan Lindberg, Yingbo Lin, Felix Haglund de Flon
PURPOSE: Tumor classification is a key component in personalized cancer care. For soft tissue and bone tumors, this classification is currently based primarily on morphology assessment and immunohistochemical staining. However, these standard-of-care methods can pose challenges for pathologists. We therefore assessed how whole-genome and whole-transcriptome sequencing (WGTS) impacted tumor classification and clinical management when interpreted together with histomorphology. EXPERIMENTAL DESIGN: We prospectively evaluated WGTS in routine diagnostics of 200 soft tissue and bone tumors suspicious for malignancy, including DNA and RNA isolation from the tumor, and DNA isolation from a peripheral blood sample or any non-tumor tissue...
April 4, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38573683/applications-and-opportunities-for-immune-cell-car-engineering-in-comparative-oncology
#16
JOURNAL ARTICLE
Antonia Rotolo, Matthew J Atherton
Chimeric antigen receptor (CAR) T adoptive cell therapy has transformed the treatment of human hematologic malignancies. However, its application for the treatment of solid tumors remains challenging. An exciting avenue for advancing this field lies in the use of pet dogs, in which cancers that recapitulate the biology, immunological features, and clinical course of human malignancies arise spontaneously. Moreover, their large size, outbred genetic background, shared environment with humans, and immunocompetency make dogs ideal for investigating and optimizing CAR therapies before human trials...
April 4, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38573059/update-on-cancer-predisposition-syndromes-and-surveillance-guidelines-for-childhood-brain-tumors
#17
JOURNAL ARTICLE
Jordan R Hansford, Anirban Das, Rose B McGee, Yoshiko Nakano, Jack Brzezinski, Sarah R Scollon, Surya P Rednam, Jaclyn Schienda, Orli Michaeli, Sun Young Kim, Mary-Louise C Greer, Rosanna Weksberg, Douglas R Stewart, William D Foulkes, Uri Tabori, Kristian W Pajtler, Stefan M Pfister, Garrett M Brodeur, Junne Kamihara
Tumors of the central nervous system (CNS) comprise the second most common group of neoplasms in childhood. The incidence of germline predisposition among children with brain tumors continues to grow as our knowledge on disease aetiology increases. Some children with brain tumors may present with non-malignant phenotypic features of specific syndromes (e.g. nevoid basal cell carcinoma syndrome, neurofibromatosis type 1 and type 2, DICER1 syndrome, and constitutional mismatch repair deficiency), while others may present with a strong family history of cancer (e...
April 4, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38568191/klrg1-another-opportunity-for-a-breakthrough-in-mtcl
#18
JOURNAL ARTICLE
Gaurav Varma, Catherine S Diefenbach
Outcomes in mature T-cell lymphomas remain poor, with previous attempts at developing monoclonal antibodies (mAb) compromised by limited efficacy and significant immunocompromise. Anti-killer cell lectin-like receptor G1 mAbs may have greater selectivity and specificity for malignant T-cells and avoid the toxicity concerns with previous agents.
April 3, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38564595/the-vegf-hypoxia-signature-is-upregulated-in-basal-like-breast-tumors-from-women-of-african-ancestry-and-associated-with-poor-outcomes-in-breast-cancer
#19
JOURNAL ARTICLE
Yoo Jane Han, Siyao Liu, Ashley Hardeman, Padma Sheila Rajagopal, Jeffrey Mueller, Galina Khramtsova, Ayodele Sanni, Mustapha A Ajani, Wendy Clayton, Ian W Hurley, Toshio F Yoshimatsu, Yonglan Zheng, Joel Parker, Charles M Perou, Olufunmilayo I Olopade
PURPOSE: Black women experience the highest breast cancer mortality rate compared to women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry. EXPERIMENTAL DESIGN: We developed a NanoString nCounter gene expression panel and applied it to breast tumors from Nigeria (n=182) and the University of Chicago (n=161)...
April 2, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38564259/clinical-challenges-of-consensus-molecular-subtype-cms4-colon-cancer-in-the-era-of-precision-medicine
#20
JOURNAL ARTICLE
Sophie Mouillet-Richard, Antoine Cazelles, Marine Sroussi, Claire Gallois, Julien Taieb, Pierre Laurent-Puig
Over the past decade, our understanding of the diversity of colorectal cancer (CRC) has expanded significantly, raising hopes of tailoring treatments more precisely for individual patients. A key achievement in this direction was the establishment of the consensus molecular classification, particularly identifying the challenging consensus molecular subtype (CMS) CMS4 associated with poor prognosis. Due to its aggressive nature, extensive research is dedicated to the CMS4 subgroup. Recent years have unveiled molecular and microenvironmental features at the tissue level specific to CMS4 CRC...
April 2, 2024: Clinical Cancer Research
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