journal
https://read.qxmd.com/read/37738033/glioma-response-to-idh-inhibition-real-world-experience
#1
JOURNAL ARTICLE
Rimas V Lukas, Craig Horbinski
Treatment of IDH mutated non-enhancing grade 2 and 3 diffuse gliomas with ivosidenib leads to reduction of tumor size when assessed via volumetric MRI. IDH inhibition has a therapeutic benefit in patients with these tumors.
September 22, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37738027/genetic-predictors-of-ibrutinib-related-cardiovascular-side-effects-in-patients-with-chronic-lymphocytic-leukemia
#2
JOURNAL ARTICLE
Issam S Hamadeh, Jai N Patel, Ryan Jacobs, Hang Zeng, Jiaxian He, Bei Hu, Tamara Kay Moyo, Amy Soni, Steven Park, Ed Copelan, Belinda Avalos, Alicia Hamilton, Nury Steuerwald, Nilanjan Ghosh
PURPOSE: Patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib are at risk of developing cardiovascular side effects (CVSEs). The molecular determinants of CVSEs have not been fully elucidated. We interrogated genetic polymorphisms in the Bruton Tyrosine Kinase (BTK) signaling pathway for their association with ibrutinib-related CVSEs. EXPERIMENTAL DESIGN: We conducted a retrospective/prospective observational pharmacogenetic study of 50 patients with newly diagnosed or relapsed CLL who received ibrutinib at a starting daily dose of 420 mg for at least six months...
September 22, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37737650/harnessing-dendritic-cells-next-frontier-for-durable-immune-control-in-myeloma
#3
JOURNAL ARTICLE
Madhav V Dhodapkar
Immune-based approaches including T-cell redirection have transformed the therapeutic landscape in myeloma. Injection of dendritic cells (DC) led to the induction of immune responses in vaccinated patients with myeloma. These studies pave the way for future combination strategies harnessing DCs to enhance tumor immunity and improve outcomes in myeloma. See related article by Freeman et al., p. 000.
September 22, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37735756/survivin-dendritic-cell-vaccine-safely-induces-immune-responses-and-is-associated-with-durable-disease-control-after-autologous-transplant-in-patients-with-myeloma
#4
JOURNAL ARTICLE
Ciara L Freeman, Reginald Atkins, Indumathy Varadarajan, Meghan Menges, Jeffrey Edelman, Rachid Baz, Jason Brayer, Omar Castaneda Puglianini, Jose Leonel Ochoa-Bayona, Taiga Nishihori, Kenneth H Shain, Bijal Shah, Dung Tsa Chen, Linda Kelley, Domenico Coppola, Melissa Alsina, Scott Antonia, Claudio Anasetti, Frederick L Locke
PURPOSE: We investigated whether a dendritic cell (DC) vaccine transduced with an adenoviral vector encoded with full-length survivin (Ad-S), with mutations neutralizing its antiapoptotic function, could safely generate an immune response and deepen clinical responses when administered before and after autologous stem cell transplant (ASCT) for multiple myeloma. PATIENTS AND METHODS: This phase I first-in-human trial (NCT02851056) evaluated the safety of DC:Ad-S in newly diagnosed multiple myeloma not having achieved complete response with induction, given 7 to 30 days prior to stem cell collection and 20 to 34 days after ASCT...
September 22, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37733830/pd-1-blockade-induces-reactivation-of-non-productive-t-cell-responses-characterized-by-nf-kb-signaling-in-patients-with-pancreatic-cancer
#5
JOURNAL ARTICLE
Lestat R Ali, Patrick J Lenehan, Victoire Cardot-Ruffino, Andressa Dias Costa, Matthew H G Katz, Todd W Bauer, Jonathan A Nowak, Brian M Wolpin, Thomas A Abrams, Anuj Patel, Thomas E Clancy, Jiping Wang, Joseph D Mancias, Matthew J Reilley, Chee-Chee H Stucky, Tanios S Bekaii-Saab, Rawad Elias, Nipun Merchant, Craig L Slingluff, Osama E Rahma, Stephanie K Dougan
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) trials have evaluated CTLA-4 and/or PD-(L)1 blockade in patients with advanced disease where bulky tumor burden and limited time to develop anti-tumor T cells may have contributed to poor clinical efficacy. Here we evaluated peripheral blood and tumor T cells from patients with PDAC receiving neoadjuvant chemoradiation plus anti-PD-1 (pembrolizumab) versus chemoradiation alone. We analyzed whether PD-1 blockade successfully reactivated T cells in the blood and/or tumor to determine whether lack of clinical benefit could be explained by lack of reactivated T cells versus other factors...
September 21, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37733811/perk-inhibition-by-hc-5404-sensitizes-renal-cell-carcinoma-tumor-models-to-antiangiogenic-tyrosine-kinase-inhibitors
#6
JOURNAL ARTICLE
Michael E Stokes, Veronica Calvo, Sho Fujisawa, Crissy Dudgeon, Sharon Huang, Nupur Ballal, Leyi Shen, Jennifer Gasparek, Matthew Betzenhauser, Simon J Taylor, Kirk A Staschke, Alan C Rigby, Mark J Mulvihill, Nandita Bose, Eric S Lightcap, David Surguladze
PURPOSE: Tumors activate protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK, also called EIF2AK3) in response to hypoxia and nutrient deprivation as a stress-mitigation strategy. Here, we tested the hypothesis that inhibiting PERK with HC-5404 enhances the antitumor efficacy of standard-of-care vascular endothelial growth factor tyrosine kinase inhibitors (VEGFR-TKIs). EXPERIMENTAL DESIGN: HC-5404 was characterized as a potent and selective PERK inhibitor, with favorable in vivo properties...
September 21, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37733800/differential-benefit-of-metronomic-chemotherapy-among-triple-negative-breast-cancer-subtypes-treated-in-the-ibcsg-trial-22-00
#7
JOURNAL ARTICLE
Andrea Joaquin Garcia, Mattia Rediti, David Venet, Samira Majjaj, Roswitha Kammler, Elisabetta Munzone, Lorenzo Gianni, Beat Thürlimann, István Láng, Marco Colleoni, Sherene Loi, Giuseppe Viale, Meredith M Regan, Laurence Buisseret, Françoise Rothé, Christos Sotiriou
PURPOSE: To explore whether specific triple-negative breast cancer (TNBC) molecular subtypes are predictive for a benefit from maintenance low-dose cyclophosphamide and methotrexate (CM) in the adjuvant IBCSG 22-00 phase III clinical trial. EXPERIMENTAL DESIGN: RNA sequencing was performed on a selection of 347 TNBC FFPE tumor samples following a case-cohort-like sampling. TNBC subtypes were computed on gene expression data. The association between TNBC subtypes and treatment outcome was assessed using a Cox proportional-hazard interaction test...
September 21, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37733794/atm-mutations-associate-with-distinct-co-mutational-patterns-and-therapeutic-vulnerabilities-in-nsclc
#8
JOURNAL ARTICLE
Natalie I Vokes, Ana Galan Cobo, Margarita Fernandez-Chas, David Molkentine, Santiago Treviño, Vitaly Druker, Yu Qian, Sonia Patel, Stephanie Schmidt, Lingzhi Hong, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Marcelo V Negrao, Don L Gibbons, Ara Vaporciyan, Xiuning Le, Jia Wu, Jianjun Zhang, Una Rigney, Sonia Iyer, Emma Dean, John V Heymach
INTRODUCTION: ATM is the most frequently mutated DNA damage repair gene in non-small cell lung cancer (NSCLC). However, the molecular correlates of ATM mutations and their clinical implications have not been fully elucidated. METHODS: Clinicopathologic and genomic data from 26,587 NSCLC patients from MD Anderson, public databases, and a de-identified nationwide (US-based) NSCLC clinico-genomic database (CGDB) were used to assess the co-mutation landscape, protein expression, and mutational processes in ATM-mutant tumors...
September 21, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37733788/near-infrared-spectral-tomography-for-predicting-residual-cancer-burden-during-early-stage-neoadjuvant-chemotherapy-for-breast-cancer
#9
JOURNAL ARTICLE
Xu Cao, Kristen E Muller, Mary D Chamberlin, Jiang Gui, Peter A Kaufman, Gary N Schwartz, Roberta M DiFlorio-Alexander, Brian W Pogue, Keith D Paulsen, Shudong Jiang
PURPOSE: The aim of this study is to investigate whether Near-Infrared Spectral Tomography (NIRST) might serve as a reliable prognostic tool to predict Residual Cancer Burden (RCB) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) based upon early treatment response measurements. EXPERIMENTAL DESIGN: A total of thirty-five breast cancer patients receiving NAC were included in this study. NIRST imaging was performed at multiple time points, including: before treatment, at end of the first cycle, at the mid-point, and post-NAC treatments...
September 21, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37733765/personalized-medicine-s-coming-of-age-one-drug-one-patient
#10
JOURNAL ARTICLE
Muzaffar H Qazilbash, Larry W Kwak
A dendritic cell/myeloma fusion vaccine, given with lenalidomide and GM-CSF, did not result in a statistically significant increase in CR rates at 1-year post-transplant but was associated with a significant increase in circulating multiple myeloma-reactive lymphocytes indicative of tumor-specific immunity.
September 21, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37733329/10-patient-trial-remarkable-responses-in-pediatric-cancers
#11
JOURNAL ARTICLE
Elaine R Mardis
A clinical trial of Nivolumab in 10 pediatric cancer patients with high tumor mutational burden demonstrated complete responses in 50% of patients. This result recapitulates multiple clinical trial results in high mutation burden adult cancers and may redefine best practice in the setting of germline DNA mismatch repair-based susceptibility.
September 21, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37732903/deuterium-magnetic-resonance-imaging-using-deuterated-water-induced-2h-tissue-labeling-allows-monitoring-cancer-treatment-at-clinical-field-strength
#12
JOURNAL ARTICLE
Hirofumi Asano, Abdelazim Elsayed Elhelaly, Fuminori Hyodo, Ryota Iwasaki, Yoshifumi Noda, Hiroki Kato, Koki Ichihashi, Hiroyuki Tomita, Masaharu Murata, Takashi Mori, Masayuki Matsuo
PURPOSE: An accurate and non-invasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H-tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice...
September 21, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37728879/tumor-infiltrating-normal-b-cells-revealed-by-immunoglobulin-repertoire-clonotype-analysis-are-highly-prognostic-and-crucial-for-antitumor-immune-responses-in-dlbcl
#13
JOURNAL ARTICLE
Zijun Y Xu-Monette, Yong Li, Thomas Snyder, Tiantian Yu, Tingxun Lu, Alexandar Tzankov, Carlo Visco, Govind Bhagat, Wenbin Qian, Karen Dybkaer, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Fredrick B Hagemeister, Yingjun Wang, Heounjeong Go, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Moller, Benjamin M Parsons, Xiangshan Fan, J Han van Krieken, Miguel A Piris, Jane N Winter, Qingyan Au, Ilan Kirsch, Mingzhi Zhang, John Shaughnessy, Bing Xu, Ken H Young
PURPOSE: Tumor-infiltrating B lymphocytes (TIL-Bs) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance. EXPERIMENTAL DESIGN: A total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes...
September 20, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37725593/advanced-age-in-humans-and-mouse-models-of-glioblastoma-show-decreased-survival-from-extratumoral-influence
#14
JOURNAL ARTICLE
Margaret Johnson, April Bell, Kristen L Lauing, Erik Ladomersky, Lijie Zhai, Manon Penco-Campillo, Yajas Shah, Elizabeth Mauer, Joanne Xiu, Theodore Nicolaides, Michael Drumm, Kathleen McCortney, Olivier Elemento, Miri Kim, Prashant Bommi, Justin T Low, Ruba Memon, Jennifer Wu, Junfei Zhao, Xinlei Mi, Michael J Glantz, Soma Sengupta, Brandyn Castro, Bakhtiar Yamini, Craig Horbinski, Darren J Baker, Theresa L Walunas, Gary E Schiltz, Rimas V Lukas, Derek A Wainwright
PURPOSE: Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68-70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant source(s) of maladaptive aging effects remains to be established. Here we studied intratumoral and extratumoral relationships between adult GBM patients and mice with brain tumors across the lifespan. EXPERIMENTAL DESIGN: Electronic health records at Northwestern Medicine and the NCI SEER databases were evaluated for GBM patient age and overall survival...
September 19, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37725585/entinostat-enhances-the-efficacy-of-chemotherapy-in-small-cell-lung-cancer-through-s-phase-arrest-and-decreased-base-excision-repair
#15
JOURNAL ARTICLE
Anna Solta, Kristiina Boettiger, Ildikó Kovács, Christian Lang, Zsolt Megyesfalvi, Franziska Ferk, Miroslav Mišík, Konrad Hoetzenecker, Clemens Aigner, Christian R Kowol, Siegfried Knasmueller, Michael Grusch, Beáta Szeitz, Melinda Rezeli, Balazs Dome, Karin Schelch
PURPOSE: Acquired chemoresistance is a frequent event in small cell lung cancer (SCLC), one of the deadliest human malignancies. Histone deacetylase inhibitors (HDACi) have been shown to synergize with different chemotherapeutic agents including cisplatin. Accordingly, we aimed to investigate the dual targeting of HDAC inhibition and chemotherapy in SCLC. EXPERIMENTAL DESIGN: The efficacy of HDACi and chemotherapy in SCLC was investigated both in vitro and in vivo...
September 19, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37725576/integration-of-genomic-sequencing-drives-therapeutic-targeting-of-pdgfra-in-t-cell-acute-lymphoblastic-leukemia-lymphoblastic-lymphoma
#16
JOURNAL ARTICLE
Jonathan Paolino, Boris Dimitrov, Beth Apsel Winger, Angelica Sandoval-Perez, Amith Vikram Rangarajan, Nicole Ocasio-Martinez, Harrison K Tsai, Yuting Li, Amanda L Robichaud, Delan Khalid, Charlie Hatton, Riaz Gillani, Petri Polonen, Anthony Dilig, Giacomo Gotti, Julia Kavanagh, Asmani A Adhav, Sean Gow, Jonathan Tsai, Yen Der Li, Benjamin L Ebert, Eliezer M Van Allen, Jacob Bledsoe, Annette S Kim, Sarah K Tasian, Stacy L Cooper, Todd M Cooper, Nobuko Hijiya, Maria Luisa Sulis, Neerav N Shukla, Jeffrey A Magee, Charles G Mullighan, Michael J Burke, Marlise R Luskin, Brenton G Mar, Matthew P Jacobson, Marian H Harris, Kimberly Stegmaier, Andrew E Place, Yana Pikman
PURPOSE: Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) have limited therapeutic options. Clinical use of genomic profiling provides an opportunity to identify targetable alterations to inform therapy. EXPERIMENTAL DESIGN: We describe a cohort of 14 pediatric patients with relapsed or refractory T-ALL enrolled on the Leukemia Precision-based Therapy (LEAP) Consortium trial (NCT02670525) and a patient with T-LBL, discovering alterations in platelet-derived growth factor receptor-α (PDGFRA) in 3 of these patients...
September 19, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37725573/novel-clinical-trial-designs-with-dose-optimization-to-improve-long-term-outcomes
#17
JOURNAL ARTICLE
Peter F Thall, Yong Zang, Andrew G Chapple, Ying Yuan, Ruitao Lin, David Marin, Pavlos Msaouel
Conventional designs for choosing a dose for a new therapy may select doses that are unsafe or ineffective, and fail to optimize progression free survival time, overall survival time, or remission duration. We explain and illustrate limitations of conventional dose finding designs, and make four recommendations to address these problems. When feasible, a dose-finding design should account for long-term outcomes, include screening rules that drop unsafe or ineffective doses, enroll an adequate sample size, and randomize patients among doses...
September 19, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37725572/rank-expression-as-an-independent-predictor-for-response-to-neoadjuvant-chemotherapy-in-luminal-like-breast-cancer-a-translational-insight-from-the-geparx-trial
#18
JOURNAL ARTICLE
Theresa Link, Jens-Uwe Blohmer, Wolfgang D Schmitt, Jan Dominik Kuhlmann, Marianne Just, Michael Untch, Oliver Stotzer, Peter A Fasching, Marc Thill, Mattea Reinisch, Andreas Schneeweiss, Pauline Wimberger, Sabine Seiler, Jens Huober, Christian Jackisch, Kerstin Rhiem, Claus Hanusch, Bruno V Sinn, Valentina Nekljudova, Sibylle Loibl, Carsten Denkert
PURPOSE: The GeparX study investigated whether denosumab as add-on treatment to nab-paclitaxel-based neoadjuvant chemotherapy (NACT) with two different schedules (125mg/m² weekly vs. day 1, 8 q22) may increase pathological complete response (pCR) rate. The addition of denosumab to NACT did not improve pCR rates as recently published. In this study, we investigated whether RANK expression, as part of the denosumab target pathway, a) may retrospectively identify a subgroup of patients with additional clinical benefit of denosumab or b) may predict response to nab-paclitaxel NACT...
September 19, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37724990/exercise-training-reduces-the-inflammatory-response-and-promotes-intestinal-mucosa-associated-immunity-in-lynch-syndrome
#19
JOURNAL ARTICLE
Nan Deng, Laura Reyes-Uribe, Johannes F Fahrmann, Whittney S Thoman, Mark F Munsell, Jennifer B Dennison, Eunice Murage, Ranran Wu, Ernest T Hawk, Selvi Thirumurthi, Patrick M Lynch, Christina M Dieli-Conwright, Alexander J Lazar, Sonali Jindal, Khoi Chu, Manoj Chelvanambi, Karen Basen-Engquist, Yisheng Li, Jennifer A Wargo, Florencia McAllister, James P Allison, Padmanee Sharma, Krishna M Sinha, Samir Hanash, Susan C Gilchrist, Eduardo Vilar
PURPOSE: Lynch Syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacological intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. EXPERIMENTAL DESIGN: To address this, we enrolled 21 LS patients onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes thrice weekly for 45 minutes versus usual care with a one-time exercise counseling session as control...
September 19, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37721526/suppression-of-tumor-cell-lactate-generating-signaling-pathways-eradicates-murine-pten-p53-deficient-aggressive-variant-prostate-cancer-via-macrophage-phagocytosis
#20
JOURNAL ARTICLE
Kiranj Chaudagar, Hanna M Hieromnimon, Anne Kelley, Brian Labadie, Jordan Shafran, Srikrishnan Rameshbabu, Catherine Drovetsky, Kaela Bynoe, Ani Solanki, Erica Markiewicz, Xiaobing Fan, Massimo Loda, Akash Patnaik
PURPOSE: PTEN loss-of-function/PI3K pathway hyperactivation is associated with poor therapeutic outcomes and immune checkpoint inhibitor resistance across multiple malignancies. Our prior studies in Pb-Cre;PTENfl/flTrp53fl/fl genetically engineered mice (GEM) with aggressive-variant prostate cancer (AVPC) demonstrated tumor growth control in 60% mice following androgen deprivation therapy (ADT)/PI3K inhibitor (PI3Ki)/PD-1 antibody combination, via abrogating lactate cross-talk between cancer cells and tumor-associated macrophages (TAM), and suppression of histone lactylation (H3K18lac)/phagocytic activation within TAM...
September 18, 2023: Clinical Cancer Research
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