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Trastuzumab: dreams, desperation and hope Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-03-15 H. Michael Shepard
The story of trastuzumab begins with Axel Ullrich’s dedication to the concept that receptor tyrosine kinases must be the key to many human diseases. It continued with H. Michael Shepard’s dedication to making a cancer therapy that attacks tumour cells, not normal cells, and Dennis Slamon’s drive to save the lives of people with breast cancer. In this World View, H. Michael Shepard describes his personal
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Racial Disparities in Receipt of Guideline-Concordant Care for Early-Onset Colorectal Cancer—We Must Do Better J. Clin. Oncol. (IF 45.3) Pub Date : 2024-03-15 Winta T. Mehtsun, Samir Gupta
Journal of Clinical Oncology, Ahead of Print.
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Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects Mol. Cancer (IF 37.3) Pub Date : 2024-03-16 Yufei Wang, Alicia Buck, Brandon Piel, Luann Zerefa, Nithyassree Murugan, Christian D. Coherd, Andras G. Miklosi, Haraman Johal, Ricardo Nunes Bastos, Kun Huang, Miriam Ficial, Yasmin Nabil Laimon, Sabina Signoretti, Zhou Zhong, Song-My Hoang, Gabriella M. Kastrunes, Marion Grimaud, Atef Fayed, Hsien-Chi Yuan, Quang-De Nguyen, Tran Thai, Elena V. Ivanova, Cloud P. Paweletz, Ming-Ru Wu, Toni K. Choueiri
One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated
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The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN Mol. Cancer (IF 37.3) Pub Date : 2024-03-16 Tao Jiang, Junwen Qi, Zhenyu Xue, Bowen Liu, Jianquan Liu, Qihang Hu, Yuqiu Li, Jing Ren, Hu Song, Yixin Xu, Teng Xu, Ruizhi Fan, Jun Song
Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT–PCR and FISH. In vitro and in vivo experiments, such as BODIPY
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Study identifies risk factors that may lead to secondary cancers CA: Cancer J. Clin. (IF 254.7) Pub Date : 2024-03-13 Mike Fillon
“Second primary cancer occurs with different frequency depending on the site of the first cancer, and we find a higher cumulative incidence in cancer sites with a relatively good or good survival. To the best of our knowledge these results are useful in the counselling of patients with cancer and the data provide new evidence for personalized survivorship care.” Trille Kristina Kjaer, PhD A study using
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Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-15 Josephine K. Dermawan, Sarah Chiang, Samuel Singer, Bhumika Jadeja, Martee L. Hensley, William D. Tap, Sujana Movva, Robert G. Maki, Cristina R. Antonescu
Purpose: Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous tumors. Despite genomic studies, current LMS risk stratification is not informed by molecular alterations. We propose a clinically applicable genomic risk stratification model. Experimental Design: We performed comprehensive genomic profiling in a cohort of 195 soft tissue LMS (STLMS), 151 primary at presentation, and a control
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Rintatolimod in Advanced Pancreatic Cancer enhances Anti-Tumor Immunity through Dendritic Cell-Mediated T Cell Responses Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-15 Casper W.F. van Eijck, Hassana el Haddaoui, Songul Kucukcelebi, Disha Vadgama, Amine Fellah, Dana A.M. Mustafa, Joachim G.J.V. Aerts, Casper H.J. van Eijck, Marcella Willemsen
Purpose: Amid the need for new approaches to improve survival in pancreatic ductal adenocarcinoma (PDAC), immune-based therapies have garnered interest. Rintatolimod, a toll-like receptor 3 (TLR-3) agonist, is a potential candidate due to its dual impact on restraining PDAC cell functions and boosting the anti-tumor immune response. This study investigates the effect of TLR-3 activation through rintatolimod
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Integrative molecular analyses of the MD Anderson prostate cancer patient-derived xenograft (MDA PCa PDX) series Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-15 Nicolas Anselmino, Estefania Labanca, Peter D.A. Shepherd, Jiabin Dong, Jun Yang, Xiaofei Song, Subhiksha Nandakumar, Ritika Kundra, Cindy J. Lee, Nikolaus Schultz, Jianhua Zhang, John C. Araujo, Ana M. Aparicio, Sumit K. Subudhi, Paul G. Corn, Louis L. Pisters, John F. Ward, John W. Davis, Elba S. Vazquez, Geraldine Gueron, Christopher J. Logothetis, Andrew Futreal, Patricia Troncoso, Yu Chen, Nora
Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer (PCa) models. This initiative builds on the rich MD Anderson (MDA) PCa patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated
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A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Grace H. Hwang, Maria F. Pazyra-Murphy, Hyuk-Soo Seo, Sirano Dhe-Paganon, Sylwia A. Stopka, Marina DiPiazza, Nizhoni Sutter, Thomas W. Gero, Alison Volkert, Lincoln Ombelets, Georgia Dittemore, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Nathalie Y.R. Agar, David A. Scott, Rosalind A. Segal
Medulloblastoma is one of the most common malignant brain tumors of children, and 30% of medulloblastomas are driven by gain-of-function genetic lesions in the Sonic Hedgehog (SHH) signaling pathway. EYA1, a haloacid dehalogenase phosphatase and transcription factor, is critical for tumorigenesis and proliferation of SHH medulloblastoma (SHH-MB). Benzarone and benzbromarone have been identified as
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NCI Cancer Research Data Commons: Cloud-based Analytical Resources Cancer Res. (IF 11.2) Pub Date : 2024-03-15 David Pot, Zelia Worman, Alexander Baumann, Shirish Pathak, Rowan Beck, Katherine Thayer, Tanja M. Davidsen, Erika Kim, Brandi Davis-Dusenbery, John Otridge, Todd Pihl, the CRDC Program, Jill S. Barnholtz-Sloan, Anthony R. Kerlavage
The NCI’s Cloud Resources (CRs) are the analytical components of the Cancer Research Data Commons (CRDC) ecosystem. This review describes how the three CRs (Broad Institute FireCloud, Institute for Systems Biology Cancer Gateway in the Cloud, and Seven Bridges Cancer Genomics Cloud) provide access and availability to large, cloud-hosted, multi-modal cancer datasets, as well as offer tools and workspaces
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NCI Cancer Research Data Commons: Resources to Share Key Cancer Data Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Zhining Wang, Tanja M. Davidsen, Gina R. Kuffel, KanakaDurga Addepalli, Amanda Bell, Esmeralda Casas-Silva, Hayley Dingerdissen, Keyvan Farahani, Andrey Fedorov, Sharon Gaheen, Robert L. Grossman, Ron Kikinis, Erika Kim, John Otridge, Todd Pihl, Melissa Porter, Henry Rodriguez, Louis M. Staudt, Ratna R. Thangudu, Sudha Venkatachari, Jean Claude Zenklusen, Xu Zhang, Jill S. Barnholtz-Sloan, the CRDC
Since 2014, the National Cancer Institute (NCI) has launched a series of data commons as part of the Cancer Research Data Commons (CRDC) ecosystem housing genomic, proteomic, imaging, and clinical data to support cancer research and promote data sharing of NCI-funded studies. This review describes each data commons (Genomic Data Commons, Proteomic Data Commons, Integrated Canine Data Commons, Cancer
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FASN Inhibition Decreases MHC-I Degradation and Synergizes with PD-L1 Checkpoint Blockade in Hepatocellular Carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Jiao Huang, Wai Ying Tsang, Xiao-Na Fang, Yu Zhang, Jie Luo, Lan-Qi Gong, Bai-Feng Zhang, Ching Ngar Wong, Zhi-Hong Li, Bei-Lei Liu, Jin-Lin Huang, Yu-Ma Yang, Shan Liu, Liu-Xian Ban, Yiu Hong Chan, Xin-Yuan Guan
Immune checkpoint inhibitors (ICI) transformed the treatment landscape of hepatocellular carcinoma (HCC). Unfortunately, patients with attenuated MHC-I expression remain refractory to ICIs, and druggable targets for upregulating MHC-I are limited. Here, we found that genetic or pharmacologic inhibition of fatty acid synthase (FASN) increased MHC-I levels in HCC cells, promoting antigen presentation
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NCI Cancer Research Data Commons: Lessons Learned and Future State Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Erika Kim, Tanja M. Davidsen, Brandi Davis-Dusenbery, Alexander Baumann, Angela Maggio, Zhaoyi Chen, Daoud Meerzaman, Esmeralda Casas-Silva, David Pot, Todd Pihl, John Otridge, Eve Shalley, the CRDC Program, Jill S. Barnholtz-Sloan, Anthony R. Kerlavage
More than ever, scientific progress in cancer research hinges on our ability to combine datasets and extract meaningful interpretations to better understand diseases and ultimately inform the development of better treatments and diagnostic tools. To enable the successful sharing and use of big data, the NCI developed the Cancer Research Data Commons (CRDC), providing access to a large, comprehensive
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AKTing on R Loops Makes for an ATRactive Target in Ovarian Cancer Therapy Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Vijayalalitha Ramanarayanan, Philipp Oberdoerffer
High-grade serous ovarian carcinoma (HGSOC) is the deadliest subtype of ovarian cancer. While PARP inhibitors (PARPi) have transformed the care of advanced HGSOC, PARPi resistance poses a major limitation to their clinical utility. DNA damage checkpoint signaling via ATR kinase can counteract PARPi-induced replication stress, making ATR an attractive therapeutic target in PARPi-resistant tumors. However
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NCI Cancer Research Data Commons: Core Standards and Services Cancer Res. (IF 11.2) Pub Date : 2024-03-15 Arthur Brady, Amanda Charbonneau, Robert L. Grossman, Heather H. Creasy, Robinette Renner, Todd Pihl, John Otridge, Erika Kim, the CRDC Program, Jill S. Barnholtz-Sloan, Anthony R. Kerlavage
The National Cancer Institute (NCI) Cancer Research Data Commons (CRDC) is a collection of data commons, analysis platforms, and tools that make existing cancer data more findable and accessible by the cancer research community. In practice, the two biggest hurdles to finding and using data for discovery are the wide variety of models and ontologies used to describe data, and the dispersed storage
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Cytoreductive nephrectomy in the era of immune checkpoint inhibitors: a U.S. FDA pooled analysis J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-03-15 Jaleh Fallah, Haley Gittleman, Chana Weinstock, Elaine Chang, Sundeep Agrawal, Shenghui Tang, Richard Pazdur, Paul G Kluetz, Daniel L Suzman, Laleh Amiri-Kordestani
Background This pooled analysis of patient-level data from trials evaluated the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with or without cytoreductive nephrectomy (CN) prior to a combination of immune checkpoint inhibitor (ICI) and anti-angiogenic therapy. Methods Five trials of ICI plus anti-angiogenic therapy were pooled. Only patients with stage 4 at initial diagnosis
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Issue Information CA: Cancer J. Clin. (IF 254.7) Pub Date : 2024-03-13
No abstract is available for this article.
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Is mandated genetic counseling needed? CA: Cancer J. Clin. (IF 254.7) Pub Date : 2024-03-13 Mike Fillon
With genetic testing becoming more readily available for cancer prevention and surveillance, a new study investigated whether skipping counseling—either before or after testing—is any worse than requiring counseling for patients with a family history of cancer or those known to be at genetic risk for cancer. The results of Making Genetic Testing Accessible (MAGENTA), a four-armed randomized clinical
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Targeting cuproplasia and cuproptosis in cancer Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-03-14 Daolin Tang, Guido Kroemer, Rui Kang
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The promise of AI in personalized breast cancer screening: are we there yet? Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-03-12 Despina Kontos
The benefits and potential harms of mammography-based screening for breast cancer are often a matter of debate. Here, I discuss the promises and limitations of a recent study that tested an artificial intelligence-based tool for the detection of breast cancer in digital mammograms in a large, prospective screening setting.
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A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation Mol. Cancer (IF 37.3) Pub Date : 2024-03-14 Xin Peng, Xin Huang, Talal Ben Lulu, Wenqing Jia, Shaolu Zhang, Limor Cohen, Shengfan Huang, Jindian Fan, Xi Chen, Shanshan Liu, Yongzhe Wang, Kailin Wang, Sho Isoyama, Shingo Dan, Feng Wang, Zhe Zhang, Moshe Elkabets, Dexin Kong
Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some
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Massive US cybersecurity breach highlights perils of health-care consolidation Lancet Oncol. (IF 51.1) Pub Date : 2024-03-14 Bryant Furlow
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First-Line Anlotinib Treatment for Soft Tissue Sarcoma in Chemotherapy-Ineligible Patients: An Open-label, Single-arm, Phase 2 Clinical Trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-14 Tao Li, Ying Dong, Yongzhong Wei, Shoufeng Wang, Yunxia Liu, Jia Chen, Wenhua Xiong, Nong Lin, Xin Huang, Meng Liu, Xiaobo Yan, Zhaoming Ye, Binghao Li
Purpose: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma (LA/M STS) is chemotherapy based on anthracyclines, but patient tolerance of chemotherapy is limited. The present trial (NCT03792542) investigated the use of anlotinib as first-line treatment for patients with advanced STS, in particular liposarcoma (LPS). Patients and Methods: Eligible patients
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Repolarization of immunosuppressive macrophages by targeting SLAMF7-regulated CCL2 signaling sensitizes hepatocellular carcinoma to immunotherapy Cancer Res. (IF 11.2) Pub Date : 2024-03-14 Jialei Weng, Zheng Wang, Zhiqiu Hu, Wenxin Xu, Jia-Lei Sun, Fu Wang, Qiang Zhou, Shaoqing Liu, Min Xu, Minghao Xu, Dongmei Gao, Ying-Hao Shen, Yong Yi, Yi Shi, Qiongzhu Dong, Chenhao Zhou, Ning Ren
Immune checkpoint inhibitors have limited efficacy in hepatocellular carcinoma (HCC). Macrophages are the most abundant immune cells in HCC, suggesting that a better understanding of the intrinsic processes by which tumor cells regulate macrophages could help identify strategies to improve response to immunotherapy. As signaling lymphocytic activation molecule (SLAM) family members regulate various
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Translational frontiers and clinical opportunities of immunologically-fitted radiotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-13 Daphné Morel, Charlotte Robert, Nikos Paragios, Vincent Grégoire, Eric Deutsch
Ionising radiations can have a wide range of impacts on tumour-immune interactions, which are being studied with the greatest interest and at an accelerating pace by the medical community. Despite its undeniable immunostimulatory potential, it clearly appears that radiotherapy as it is prescribed and delivered nowadays often alters the host’s immunity towards a suboptimal state. This may impair the
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New pathogen on the block Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-03-11 Anna Dart
Fu et al. provide data indicating a pathogenic role for Streptococcus anginosus in gastric cancer.
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Infiltrative vessel co-optive growth pattern induced by IQGAP3 overexpression promotes microvascular invasion in hepatocellular carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-12 Miaoling Tang, Shuxia Zhang, Meisongzhu Yang, Rongni Feng, Jinbin Lin, Xiaohong Chen, Yingru Xu, Ruyuan Yu, Xinyi Liao, Ziwen Li, Xincheng Li, Man Li, Qiliang Zhang, Suwen Chen, Wanying Qian, Yuanji Liu, Libing Song, Jun Li
Purpose: Microvascular invasion (MVI) is a major unfavorable prognostic factor for intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). However, the intervention and preoperative prediction for MVI remain clinical challenges due to the absent precise mechanism and molecular marker(s). Herein, we aimed to investigate the mechanisms underlying vascular invasion that
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Polo-like kinase 1 inhibition in KRAS-mutated metastatic colorectal cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-12 Justin Stebbing, Andrea J. Bullock
Inhibition of Polo-like kinase 1 (Plk1) is a promising new target and therapeutic strategy in metastatic colorectal cancer, especially those with KRAS mutations. New data support further development of onvansertib, and highlights the role of circulating tumor DNA in phase 1 clinical trials.
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Cell-free DNA concentration as a biomarker of response and recurrence in HER2-negative breast cancer receiving neoadjuvant chemotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-12 Mark Jesus M. Magbanua, Ziad Ahmed, Rosalyn W. Sayaman, Lamorna Brown Swigart, Gillian L. Hirst, Christina Yau, Denise M. Wolf, Wen Li, Amy L. Delson, Jane Perlmutter, Paula Pohlmann, W. Fraser. Symmans, Douglas Yee, Nola M. Hylton, Laura J. Esserman, Angela M. DeMichele, Hope S. Rugo, Laura J. van 't Veer
Purpose: We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients. Experimental Design: 145 hormone receptor (HR)-positive/HER2-negative and
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Whole-genome DNA methylation profiling of intrahepatic cholangiocarcinoma reveals prognostic subtypes with distinct biological drivers Cancer Res. (IF 11.2) Pub Date : 2024-03-12 Haotian Liao, Xing Chen, Haichuan Wang, Youpei Lin, Lu Chen, Kefei Yuan, Mingheng Liao, Hanyu Jiang, Jiajie Peng, Zhenru Wu, Jiwei Huang, Jiaxin Li, Yong Zeng
Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer. While the genetic characterization of iCCA has led to targeted therapies for treating tumors with FGFR2 alterations and IDH1/2 mutations, only a limited number of patients can benefit from these strategies. Epigenomic profiles have emerged as potential diagnostic and prognostic biomarkers for improving treatment
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SPARC stabilizes ApoE to induce cholesterol-dependent invasion and sorafenib resistance in hepatocellular carcinoma Cancer Res. (IF 11.2) Pub Date : 2024-03-12 Shan Wan, Quan-Yao He, Yun Yang, Feng Liu, Xue Zhang, Xin Guo, Hui Niu, Yi Wang, Yi-Xuan Liu, Wen-Long Ye, Xiu-Ming Li, Xue-Mei ZhuanSun, Pu Sun, Xiao-Shun He, Guang Hu, Kai Breuhahn, Hua Zhao, Guo-Qiang Wu, Hua Wu
Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastasis. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular
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ACSL4-mediated membrane phospholipid remodeling induces integrin β1 activation to facilitate triple-negative breast cancer metastasis Cancer Res. (IF 11.2) Pub Date : 2024-03-12 Yuxiang Qiu, Xing Wang, Yan Sun, Ting Jin, Rui Tang, Xinyue Zhou, Ming Xu, Yubi Gan, Rui Wang, Haojun Luo, Manran Liu, Xi Tang
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and has a poor prognosis and a high propensity to metastasize. Lipid metabolism has emerged as a critical regulator of tumor progression and metastasis in other cancer types. Characterization of the lipid metabolic features of TNBC could provide important insights into the drivers of TNBC metastasis. Here, we showed
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A histone methylation-MAPK signaling axis drives durable epithelial-mesenchymal transition in hypoxic pancreatic cancer Cancer Res. (IF 11.2) Pub Date : 2024-03-12 Brooke A. Brown, Paul J. Myers, Sara J. Adair, Jason R. Pitarresi, Shiv K. Sah-Teli, Logan A. Campbell, William S. Hart, Michelle C. Barbeau, Kelsey Leong, Nicholas Seyler, William Kane, Kyoung Eun Lee, Edward Stelow, Marieke Jones, M. Celeste Simon, Peppi Koivunen, Todd W. Bauer, Ben Z. Stanger, Matthew J. Lazzara
The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) plays a key role in tumor progression and response to therapy. The dense PDAC stroma causes hypovascularity, which leads to hypoxia. Here, we showed that hypoxia drives long-lasting epithelial-mesenchymal transition (EMT) in PDAC primarily through a positive-feedback histone methylation-MAPK signaling axis. Transformed cells preferentially
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Potential role of cannabis in ameliorating observed racialized disparities in cancer pain management J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-03-12 Laurel P Gibson, Rebecca A Ferrer, Salimah H Meghani, Amanda M Acevedo
Cancer-related pain affects a significant proportion of all cancer patients yet remains inadequately managed, particularly among cancer patients from racialized backgrounds. In recent years, there has been increased research and clinical interest in the use of medical cannabis for cancer pain management, including its potential to ameliorate racialized disparities in cancer pain control. Although medical
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Familial adversity: association with discontinuation of adjuvant hormone therapy and breast cancer prognosis J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-03-12 Erwei Zeng, Wei He, Arvid Sjölander, Jenny Bergqvist, Fang Fang, Kamila Czene
Background Many studies have examined patient-related factors affecting adjuvant hormone therapy adherence in breast cancer patients. Our study aimed to examine associations of family-related factors with adjuvant hormone therapy discontinuation and breast cancer-specific mortality. Methods By cross-linking seven Swedish health registers, we performed a cohort study including all breast cancer patients
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The construction of modular universal chimeric antigen receptor T (MU-CAR-T) cells by covalent linkage of allogeneic T cells and various antibody fragments Mol. Cancer (IF 37.3) Pub Date : 2024-03-11 Tao Chen, Jieyi Deng, Yongli Zhang, Bingfeng Liu, Ruxin Liu, Yiqiang Zhu, Mo Zhou, Yingtong Lin, Baijin Xia, Keming Lin, Xiancai Ma, Hui Zhang
Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. Here, we tried
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Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs Mol. Cancer (IF 37.3) Pub Date : 2024-03-09 Xiaojun Shi, Shiyu Pang, Jiawei Zhou, Guang Yan, Ruxi Gao, Haowei Wu, Zhou Wang, Yuqing Wei, Xinyu Liu, Wanlong Tan
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is one of the causes of tumor immune tolerance and failure of cancer immunotherapy. Here, we found that bladder cancer (BCa)-derived exosomal circRNA_0013936 could enhance the immunosuppressive activity of PMN-MDSCs by regulating the expression of fatty acid transporter protein 2 (FATP2) and receptor-interacting protein kinase 3 (RIPK3)
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Correction: Aurora kinase targeting in lung cancer reduces KRAS-induced transformation Mol. Cancer (IF 37.3) Pub Date : 2024-03-09 Edmilson Ozorio dos Santos, Tatiana Correa Carneiro-Lobo, Mateus Nobrega Aoki, Elena Levantini, Daniela Sanchez Bassères
Correction: Mol Cancer 15, 12 (2016) https://doi.org/10.1186/s12943-016-0494-6 Following publication of the original article [1], the authors identified an error in Fig. 1f. The correct and incorrect figures are given below. Incorrect Fig. 1: Correct Fig. 1: Fig. 1 shRNA-mediated knockdown of AURKA or AURKB decreases the transformed phenotype of KRAS-positive lung cells. Unless otherwise indicated
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Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine Mol. Cancer (IF 37.3) Pub Date : 2024-03-09 Anmi Jose, Pallavi Kulkarni, Jaya Thilakan, Murali Munisamy, Anvita Gupta Malhotra, Jitendra Singh, Ashok Kumar, Vivek M. Rangnekar, Neha Arya, Mahadev Rao
Despite advancements in treatment protocols, cancer is one of the leading cause of deaths worldwide. Therefore, there is a need to identify newer and personalized therapeutic targets along with screening technologies to combat cancer. With the advent of pan-omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics, the scientific community has witnessed an improved
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Tumor-infiltrating lymphocytes refine outcomes in triple-negative breast cancer treated with anthracycline-free neoadjuvant chemotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-11 Miguel Martín, Rachel Yoder, Roberto Salgado, Maria del Monte-Millán, Enrique L. Alvarez, Isabel Echavarría, Joshua M. Staley, Anne P. O'Dea, Lauren E. Nye, Shane R. Stecklein, Coralia Bueno Muiño, Yolanda Jerez-Gilarranz, María Cebollero, Oscar Bueno, Jose Ángel. Garcia-Saenz, Fernando Moreno, Uriel Bohn, Henry Gomez, Tatiana Massarrah, Qamar J. Khan, Andrew K. Godwin, Sara López-Tarruella, Priyanka
Background: Stromal tumor-infiltrating lymphocytes (sTILs) are associated with pathologic complete response (pCR) and long-term outcomes for triple-negative breast cancer (TNBC) in setting of anthracycline-based chemotherapy. Impact of sTILs on refining outcomes beyond prognostic information provided by pCR in anthracycline-free neoadjuvant chemotherapy (NAC) is not known. Patients & Methods: This
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Biomarkers of efficacy and safety of the academic BCMA-CART ARI0002h for the treatment of refractory multiple myeloma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-11 Aina Oliver-Caldés, Marta Español-Rego, Aintzane Zabaleta, Veronica Gonzalez-Calle, Sergio Navarro-Velázquez, Susana Inoges, Ascensión López-Díaz de Cerio, Valentin Cabañas, Nieves López-Muñoz, Paula Rodriguez-Otero, Juan Luis. Reguera-Ortega, David F. Moreno, Núria Martínez-Cibrian, Lucía López-Corral, Lorena Pérez-Amill, Beatriz Martin-Antonio, Laura Rosinol, Joan Cid, Natalia Tovar, Joaquin Saez-Peñataro
Background: BCMA-CARTs improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to
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Predicting five-year interval second breast cancer risk in women with prior breast cancer J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-03-11 Rebecca A Hubbard, Yu-Ru Su, Erin Ja Bowles, Laura Ichikawa, Karla Kerlikowske, Kathryn P Lowry, Diana L Miglioretti, Anna N A Tosteson, Karen J Wernli, Janie M Lee
Background Annual surveillance mammography is recommended for women with a personal history of breast cancer. Risk prediction models that estimate mammography failures such as interval second breast cancers could help to tailor surveillance imaging regimens to women’s individual risk profiles. Methods In a cohort of women with a history of breast cancer receiving surveillance mammography in the Breast
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Frameshift mutations in peripheral blood as a biomarker for surveillance of lynch syndrome J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-03-11 Yurong Song, Holli Loomans-Kropp, Ryan N Baugher, Brandon Somerville, Shaneen S Baxter, Travis D Kerr, Teri M Plona, Stephanie D Mellott, Todd B Young, Heidi E Lawhorn, Lei Wei, Qiang Hu, Song Liu, Alan Hutson, Ligia Pinto, John D Potter, Shizuko Sei, Ozkan Gelincik, Steven M Lipkin, Johannes Gebert, Matthias Kloor, Robert H Shoemaker
Background Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, which lead to high microsatellite instability (MSI-H) and frameshift mutations (FSMs) at coding mononucleotide repeats (cMNRs) in the genome. Recurrent FSMs in these regions are thought to play a central role in the increased risk of various cancers. However
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Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-03-07 Pascal Meier, Arnaud J. Legrand, Dieter Adam, John Silke
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FIRSTMAPPP prospectively charts the efficacy of sunitinib for phaeochromocytoma and paraganglioma Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-03-08 David Killock
Metastatic phaeochromocytomas and paragangliomas are very rare neuroendocrine cancers that occur in <1 per million individuals. A variety of treatment modalities have been used to manage these cancers, but with limited success and based on weak evidence. Now, the results of FIRSTMAPPP — probably the first randomized trial in this setting — demonstrate the efficacy of sunitinib. Owing to the potentially
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Impact of Risk-Based therapy on late morbidity and mortality in neuroblastoma survivors: a report from the childhood cancer survivor study J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-03-09 Danielle Novetsky Friedman, Pamela J Goodman, Wendy M Leisenring, Lisa R Diller, Susan L Cohn, Rebecca M Howell, Susan A Smith, Emily S Tonorezos, Suzanne L Wolden, Joseph P Neglia, Kirsten K Ness, Todd M Gibson, Paul C Nathan, Lucie M Turcotte, Brent R Weil, Leslie L Robison, Kevin C Oeffinger, Gregory T Armstrong, Charles A Sklar, Tara O Henderson
Background Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences have not been well-described. Methods Late mortality, subsequent malignant neoplasms (SMN), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year CCSS survivors of neuroblastoma
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Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression Mol. Cancer (IF 37.3) Pub Date : 2024-03-08 Cuncan Deng, Mingyu Huo, Hongwu Chu, Xiaomei Zhuang, Guofei Deng, Wenchao Li, Hongfa Wei, Leli Zeng, Yulong He, Huashan Liu, Jia Li, Changhua Zhang, Hengxing Chen
Circular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs in controlling macrophage function remains elusive. Exosomes serve as cargo for circRNAs and play a crucial role as mediators in facilitating communication between cancer cells and the tumor microenvironment. In this study, we found that circATP8A1, a previously unreported circular RNA, is
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Activation of the PI3K/AKT signaling pathway by ARNTL2 enhances cellular glycolysis and sensitizes pancreatic adenocarcinoma to erlotinib Mol. Cancer (IF 37.3) Pub Date : 2024-03-08 Weiyu Ge, Yanling Wang, Ming Quan, Tiebo Mao, Evelyne Y. Bischof, Haiyan Xu, Xiaofei Zhang, Shumin Li, Ming Yue, Jingyu Ma, Haiyan Yang, Lei Wang, Zhengyuan Yu, Liwei Wang, Jiujie Cui
Pancreatic adenocarcinoma (PC) is an aggressive malignancy with limited treatment options. The poor prognosis primarily stems from late-stage diagnosis and when the disease has become therapeutically challenging. There is an urgent need to identify specific biomarkers for cancer subtyping and early detection to enhance both morbidity and mortality outcomes. The addition of the EGFR tyrosine kinase
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circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis Mol. Cancer (IF 37.3) Pub Date : 2024-03-08 Yan Zhao, Yunlong Jia, Jiali Wang, Xiaolin Chen, Jingya Han, Shuman Zhen, Shuxian Yin, Wei Lv, Fan Yu, Jiaqi Wang, Fan Xu, Xinming Zhao, Lihua Liu
Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung cancer (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating the activated phenotype of fibroblasts is a promising strategy for cancer therapy. However, the underlying mechanisms of fibroblast activation and phenotype switching that drive metastasis remain
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Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response Mol. Cancer (IF 37.3) Pub Date : 2024-03-08 Hailong Qi, Zhongjie Sun, Tianle Gao, Yanling Yao, Yu Wang, Weiwei Li, Xudong Wang, Xiaofang Wang, Defang Liu, Jian-Dong Jiang
Nucleic acid vaccines have shown promising potency and efficacy for cancer treatment with robust and specific T-cell responses. Improving the immunogenicity of delivered antigens helps to extend therapeutic efficacy and reduce dose-dependent toxicity. Here, we systematically evaluated chemokine-fused HPV16 E6/E7 antigen to improve the cellular and humoral immune responses induced by nucleotide vaccines
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Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial Lancet Oncol. (IF 51.1) Pub Date : 2024-03-08 Arnon P Kater MD, Önder Arslan MD, Fatih Demirkan MD, Yair Herishanu MD, Burhan Ferhanoglu MD, Marcos Gonzalez Diaz MD, Brian Leber MD, Marco Montillo MD, Panayiotis Panayiotidis MD, Davide Rossi PhD, Alan Skarbnik MD, Adrian Tempescul PhD, Mehmet Turgut MD, Clemens H Mellink PhD, Anne-Marie F van der Kevie-Kersemaekers PhD, Stuart Lanham PhD, Ben Sale MSc, Luis Del Rio MSc, Relja Popovic MD, Brenda
Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment.
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Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations Cancer Discov. (IF 28.2) Pub Date : 2024-03-08 Azadeh C. Bashi, Elizabeth A. Coker, Krishna C. Bulusu, Patricia Jaaks, Claire Crafter, Howard Lightfoot, Marta Milo, Katrina McCarten, David F. Jenkins, Dieudonne van der Meer, James T. Lynch, Syd Barthorpe, Courtney L. Andersen, Simon T. Barry, Alexandra Beck, Justin Cidado, Jacob A. Gordon, Caitlin Hall, James Hall, Iman Mali, Tatiana Mironenko, Kevin Mongeon, James Morris, Laura Richardson, Paul
Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes. We present data for 109 anticancer drug combinations from AstraZeneca's oncology small molecule portfolio
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Phase 1/2 study of combined BCL-xL and MEK inhibition with navitoclax and trametinib in KRAS or NRAS mutant advanced solid tumors Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-08 Ryan B. Corcoran, Khanh T. Do, Jeong E. Kim, James M. Cleary, Aparna R. Parikh, Oladapo O. Yeku, Niya Xiong, Colin D. Weekes, Jennifer Veneris, Leanne G. Ahronian, Gianluca Mauri, Jun Tian, Bryanna L. Norden, Alexa G. Michel, Emily E. Van Seventer, Giulia Siravegna, Kyle Camphausen, Gary Chi, Isobel J. Fetter, Joan S. Brugge, Helen X. Chen, Naoko Takebe, Richard T. Penson, Dejan Juric, Keith T. Flaherty
Purpose: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi. Patients and Methods: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts
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A phase II open-label randomized clinical trial of preoperative durvalumab or durvalumab plus tremelimumab in resectable head and neck squamous cell carcinoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-08 Chang Gon Kim, Min Hee Hong, Dahee Kim, Brian Hyohyoung. Lee, Hyunwook Kim, Chan-Young Ock, Geoffrey Kelly, Yoon Ji Bang, Gamin Kim, Jung Eun Lee, Chaeyeon Kim, Se-Heon Kim, Hyun Jun Hong, Young Min Park, Nam Suk Sim, Heejung Park, Jin Woo Park, Chang Geol Lee, Kyung Hwan Kim, Goeun Park, Inkyung Jung, Dawoon Han, Jong Hoon Kim, Junha Cha, Insuk Lee, Mingu Kang, Heon Song, Chiyoon Oum, Seulki Kim,
Purpose: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Patients and Methods: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiation
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Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-03-08 Yusuke Nagasaki, Tetsuro Taki, Kotaro Nomura, Kenta Tane, Tomohiro Miyoshi, Joji Samejima, Keiju Aokage, Seiyu Jeong-Yoo Ohtani-Kim, Motohiro Kojima, Shingo Sakashita, Naoya Sakamoto, Shumpei Ishikawa, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii
Objective We quantified the pathological spatial intratumor heterogeneity (ITH) of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non-small cell lung carcinoma (NSCLC). Materials and methods This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA–IIIB. To characterize the spatial ITH of
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Non-inferiority of simple versus radical hysterectomy in low-risk cervical cancer Nat. Rev. Clin. Oncol. (IF 78.8) Pub Date : 2024-03-06 Diana Romero
Radical hysterectomy is recommended for women with early stage cervical cancer, although the need for extensive surgery in those with FIGO stage IA2–IB1 disease that meets criteria for low risk (limited stromal invasion and no pelvic node involvement) is questionable based on retrospective evidence indicating that parametrial invasion is very rare in these patients. Now, the results of the phase III
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Alabama Supreme Court's “extrauterine children” decision alarms oncologists and fertility experts Lancet Oncol. (IF 51.1) Pub Date : 2024-03-07 B, r, y, a, n, t, , F, u, r, l, o, w
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Non-communicable diseases in humanitarian settings Lancet Oncol. (IF 51.1) Pub Date : 2024-03-07 T, a, l, h, a, , B, u, r, k, i
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Innovation in gynaecological cancer: highlighting global disparities Lancet Oncol. (IF 51.1) Pub Date : 2024-03-07 Maria Kyrgiou, Sarah Bowden, Lynette Denny, Anna Fagotti, Nadim R Abu-Rustum, Pedro T Ramirez, Denis Querleu
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Therapeutic Targeting of TIM-4-L With Engineered T Cells for Acute Myeloid Leukemia Clin. Cancer Res. (IF 11.5) Pub Date : 2024-03-07 Brandon Cieniewicz, Edson Oliveira, Mike Saxton, Damoun Torabi, Ankit Bhatta, Phanidhar Kukutla, Alexander Arballo, Zhuo Yang, Bi Yu, Maria Fate, Hongxiu Ning, Lawrence Corey, Abhishek Maiti, Daniel Corey
Purpose: Disruption of lipid bilayer asymmetry is a common feature observed in cancer cells and offers novel routes for therapeutic targeting. We utilized the natural immune receptor TIM-4 to interrogate for loss of plasma membrane phospholipid polarity in primary acute myelogenous leukemia (AML) samples and evaluated the anti-leukemic activity of TIM-4-L-directed T cell therapy in preclinical AML