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Taking a detour Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-05-16 Anna Dart
Kong et al. have now shown that Knudson’s two-hit hypothesis can be circumvented through the actions of the glycolytic metabolite methylglyoxal, which transiently inactivates the tumour-suppressive functions of BRCA2 leading to episodic mutagenesis and cancer genome evolution.
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Finding the truth in science Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-05-16 Elisabeth M. Bik
In a ‘publish or perish’ culture, some scientists may resort to questionable research practices or even fraud. Scientific paper mills and artificial intelligence increasingly threaten the pursuit of truth in science. Structural changes, including heightened scrutiny of papers and authorship and better funding, are needed to ensure scientific integrity.
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A guide to artificial intelligence for cancer researchers Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-05-16 Raquel Perez-Lopez, Narmin Ghaffari Laleh, Faisal Mahmood, Jakob Nikolas Kather
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RICTOR/mTORC2 downregulation in BRAFV600E melanoma cells promotes resistance to BRAF/MEK inhibition Mol. Cancer (IF 37.3) Pub Date : 2024-05-16 Luca Ponzone, Valentina Audrito, Claudia Landi, Enrico Moiso, Chiara Levra Levron, Sara Ferrua, Aurora Savino, Nicoletta Vitale, Massimiliano Gasparrini, Lidia Avalle, Lorenza Vantaggiato, Enxhi Shaba, Beatrice Tassone, Stefania Saoncella, Francesca Orso, Daniele Viavattene, Eleonora Marina, Irene Fiorilla, Giulia Burrone, Youssef Abili, Fiorella Altruda, Luca Bini, Silvia Deaglio, Paola Defilippi
The main drawback of BRAF/MEK inhibitors (BRAF/MEKi)-based targeted therapy in the management of BRAF-mutated cutaneous metastatic melanoma (MM) is the development of therapeutic resistance. We aimed to assess in this context the role of mTORC2, a signaling complex defined by the presence of the essential RICTOR subunit, regarded as an oncogenic driver in several tumor types, including MM. After analyzing
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DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma Mol. Cancer (IF 37.3) Pub Date : 2024-05-16 Yangfan Liu, Yu Sun, Jin Yang, Deyang Wu, Shuang Yu, Junjiang Liu, Tao Hu, Jingjing Luo, Hongmei Zhou
The faithful maintenance of DNA methylation homeostasis indispensably requires DNA methyltransferase 1 (DNMT1) in cancer progression. We previously identified DNMT1 as a potential candidate target for oral squamous cell carcinoma (OSCC). However, how the DNMT1- associated global DNA methylation is exploited to regulate OSCC remains unclear. The shRNA-specific DNMT1 knockdown was employed to target
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NEMO/NF-κB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer Mol. Cancer (IF 37.3) Pub Date : 2024-05-16 Miltiadis Tsesmelis, Ulrike F. G. Büttner, Melanie Gerstenlauer, Uta Manfras, Konstantinos Tsesmelis, Ziwei Du, Nadine Sperb, Stephanie Ellen Weissinger, Peter Möller, Thomas F. E. Barth, Harald J. Maier, Lap Kwan Chan, Thomas Wirth
Pancreatic ductal adenocarcinoma (PDAC) is marked by a dismal survival rate, lacking effective therapeutics due to its aggressive growth, late-stage diagnosis, and chemotherapy resistance. Despite debates on NF-κB targeting for PDAC treatment, no successful approach has emerged. To elucidate the role of NF-κB, we ablated NF-κB essential modulator (NEMO), critical for conventional NF-κB signaling, in
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CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation Mol. Cancer (IF 37.3) Pub Date : 2024-05-16 Yaming Li, Zekun Wang, Jingwen Yang, Yuhan Sun, Yinqiao He, Yuping Wang, Xi Chen, Yiran Liang, Ning Zhang, Xiaolong Wang, Wenjing Zhao, Guohong Hu, Qifeng Yang
Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome
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CRISPR-Cas13d screens identify KILR, a breast cancer risk-associated lncRNA that regulates DNA replication and repair Mol. Cancer (IF 37.3) Pub Date : 2024-05-15 Lu Wang, Mainá Bitar, Xue Lu, Sebastien Jacquelin, Sneha Nair, Haran Sivakumaran, Kristine M. Hillman, Susanne Kaufmann, Rebekah Ziegman, Francesco Casciello, Harsha Gowda, Joseph Rosenbluh, Stacey L. Edwards, Juliet D. French
Long noncoding RNAs (lncRNAs) have surpassed the number of protein-coding genes, yet the majority have no known function. We previously discovered 844 lncRNAs that were genetically linked to breast cancer through genome-wide association studies (GWAS). Here, we show that a subset of these lncRNAs alter breast cancer risk by modulating cell proliferation, and provide evidence that a reduced expression
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Arming Vδ2 T cells with chimeric antigen receptors to combat cancer Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-15 Pauline Thomas, Pierre Paris, Claire Pecqueur
Immunotherapy has emerged as a promising approach in the field of cancer treatment, with chimeric antigen receptor (CAR) T cell therapy demonstrating remarkable success. However, challenges such as tumor antigen heterogeneity, immune evasion, and limited persistence of CAR-T cells have prompted the exploration of alternative cell types for CAR-based strategies. Gamma delta T cells, a unique subset
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Striking the Balance with a PD-L1×4–1BB Bispecific Antibody Cancer Res. (IF 11.2) Pub Date : 2024-05-15 JongHoon Ha, Adam J. Grippin, Betty Y.S. Kim, Wen Jiang
Antibody-based immune checkpoint blockade therapy has revolutionized the field of cancer immunotherapy, yet its efficacy remains limited in immunologically cold tumors. Combining checkpoint inhibitors with costimulatory agonists improves tumoricidal activity of T cells but also can lead to off-target hepatotoxicity. Although bispecific antibodies confer tumor selectivity to alleviate undesirable adverse
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Overcoming Nutrient Stress: Integrin αvβ3-Driven Metabolic Adaptation Supports Tumor Initiation Cancer Res. (IF 11.2) Pub Date : 2024-05-15 Elena Rainero
Nutrient stress accompanies several stages of tumor progression, including metastasis formation. Metabolic reprogramming is a hallmark of cancer, and it has been associated with stress tolerance and anchorage-independent cell survival. Adaptive responses are required to support cancer cell survival under these conditions. In this issue of Cancer Research, Nam and colleagues showed that the extracellular
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HiChIP-based Epigenomic Footprinting Identifies a Promoter Variant of UXS1 that Confers Genetic Susceptibility to Gastroesophageal Cancer. Cancer Res. (IF 11.2) Pub Date : 2024-05-15 Ansley Gnanapragasam, Eftyhios Kirbizakis, Anna Li, Kyle H. White, Katelyn L. Mortenson, Juliana Cavalcante de Moura, Wajih Jawhar, Yifei Yan, Reilly Falter, Colleen Russett, Betty Giannias, Sophie Camilleri-Broët, Nicholas Bertos, Jonathan Cools-Lartigue, Livia Garzia, Veena Sangwan, Lorenzo E. Ferri, Xiaoyang Zhang, Swneke D. Bailey
Genome-wide association studies (GWAS) have identified more than a hundred single nucleotide variants (SNVs) associated with the risk of gastroesophageal cancer (GEC). The majority of the identified SNVs map to noncoding regions of the genome. Uncovering the causal SNVs and the genes they modulate could help improve GEC prevention and treatment. Here, we used HiChIP against histone 3 lysine 27 acetylation
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The DRAP1/DR1 Repressor Complex Increases mTOR Activity to Promote Progression and Confer Everolimus Sensitivity in Triple-Negative Breast Cancer Cancer Res. (IF 11.2) Pub Date : 2024-05-15 Min-Ying Huang, Shu-Yuan Hu, Jia Dong, Ling Deng, Lisa Andriani, Xiao-Yan Ma, Yin-Ling Zhang, Fang-Lin Zhang, Zhi-Ming Shao, Da-Qiang Li
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Transcriptional dysregulation is a hallmark of cancer, and several transcriptional regulators have been demonstrated to contribute to cancer progression. Here, we identified upregulation of the transcriptional corepressor DRAP1 in TNBC, which was closely associated with poor recurrence-free survival in TNBC patients
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Correction: Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340 Mol. Cancer (IF 37.3) Pub Date : 2024-05-14 Xiangyu Jian, Han He, Jiehong Zhu, Qi Zhang, Zhongxin Zheng, Xiangjing Liang, Liuyan Chen, Meiling Yang, Kaiyue Peng, Zhaowen Zhang, Tengfei Liu, Yaping Ye, Hongli Jiao, Shuyang Wang, Weijie Zhou, Yanqing Ding, Tingting Li
Correction: Mol Cancer 19, 20 (2020) https://doi.org/10.1186/s12943-020-1134-8 Following publication of the original article [1], the authors would like to request for the below changes. 1. We request to replace the misused image in Fig.2H-Scramble-96h with the correct image. Figure 2H 2. We request to replace the misused images of Fig. 3I-circ001680+miR340 and 3L-ki67- circ001680+miR340 with the correct
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Perivascular NOTCH3+ stem cells drive meningioma tumorigenesis and resistance to radiotherapy Cancer Discov. (IF 28.2) Pub Date : 2024-05-14 Abrar Choudhury, Martha A. Cady, Calixto-Hope G. Lucas, Hinda Najem, Joanna J. Phillips, Brisa Palikuqi, Naomi Zakimi, Tara Joseph, Janeth Ochoa. Birrueta, William C. Chen, Nancy Ann Oberheim Bush, Shawn L. Hervey-Jumper, Ophir D. Klein, Christine M. Toedebusch, Craig M. Horbinski, Stephen T. Magill, Aparna Bhaduri, Arie Perry, Peter J. Dickinson, Amy B. Heimberger, Alan Ashworth, Elizabeth E. Crouch
Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas are limited to surgery and radiotherapy, and systemic therapies remain ineffective or experimental. Resistance to radiotherapy is common in high-grade meningiomas and the cell types and signaling mechanisms that drive meningioma tumorigenesis and resistance to radiotherapy are incompletely understood
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Anti-4-1BB×PD-L1 Bispecific Antibody Reinvigorates Tumor-Specific Exhausted CD8+ T Cells and Enhances the Efficacy of Anti-PD-1 Blockade Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-14 Seung Hyuck Jeon, Gihoon You, Junsik Park, Youseung Chung, Kyungjin Park, Hyunjoo Kim, Jaehyoung Jeon, Youngkwang Kim, Woo-Chan Son, Da Som Jeong, Eui-Cheol Shin, Jung-Yun Lee, Dai Hoon Han, Jaeho Jung, Su-Hyung Park
Purpose: To overcome the limited efficacy of immune checkpoint blockade, there is a need to find novel cancer immunotherapeutic strategies for the optimal treatment of cancer. The novel anti-4-1BB×PD-L1 bispecific antibody—ABL503 (also known as TJ-L14B)—was designed to simultaneously target PD-L1 and 4-1BB, and demonstrated strong antitumor T-cell responses without considerable toxicity. Here, we investigated
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Project Optimus elicits the "holistic" benefits of PK/PD modeling of immunotherapy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-14 Mathangi Gopalakrishnan, Rodabe N. Amaria
Leveraging a heterogeneous dataset, a recent article demonstrated the application of pharmacometric modeling to inform dosing of nivolumab-relatlimab fixed-dose combination in special populations, including adolescents lacking clinical data. Use of model-informed approaches during clinical drug development can be cost effective, ensuring faster access to drugs, thus enhancing patient outcomes.
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Bystander effects, pharmacokinetics, and linker-payload stability of EGFR-targeting antibody-drug conjugates Losatuxizumab vedotin and Depatux-M in glioblastoma models Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-14 Sonia Jain, Jessica I. Griffith, Kendra A. Porath, Sneha Rathi, Jiayan Le, Tugce I. Pasa, Paul A. Decker, Shiv K. Gupta, Zeng Hu, Brett L. Carlson, Katrina Bakken, Danielle M. Burgenske, Thomas M. Feldsien, Didier R. Lefebvre, Rachael A. Vaubel, Jeanette E. Eckel-Passow, Edward B. Reilly, William F. Elmquist, Jann N. Sarkaria
Purpose: Antibody-drug conjugates (ADCs) are targeted therapies with robust efficacy in solid cancers, and there is intense interest in using EGFR-specific ADCs to target EGFR-amplified glioblastoma (GBM). Given the molecular heterogeneity of GBM, bystander activity of ADCs may be important for determining treatment efficacy. In this study, the activity and toxicity of two EGFR-targeted ADCs, Losatuxizumab
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Association between oral targeted cancer drug net health benefit, uptake, and spending J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-05-14 Kelsey S Lau-Min, Yaxin Wu, Shavon Rochester, Justin E Bekelman, Genevieve P Kanter, Kelly D Getz
Background Targeted cancer drugs (TCDs) have revolutionized oncology but vary in clinical benefit and patient out-out-pocket (OOP) costs. The ASCO Value Framework uses survival, toxicity, and symptom palliation data to quantify the net health benefit (NHB) of cancer drugs. We evaluated associations between NHB, uptake, and spending on oral TCDs. Methods We conducted a retrospective cohort study of
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Health insurance among survivors of childhood cancer following affordable care act implementation J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-05-14 Anne C Kirchhoff, Austin R Waters, Qi Liu, Xu Ji, Yutaka Yasui, K Robin Yabroff, Rena M Conti, I-Chan Huang, Tara Henderson, Wendy M Leisenring, Gregory T Armstrong, Paul C Nathan, Elyse R Park
Background The Affordable Care Act (ACA) increased private non-employer health insurance options, expanded Medicaid eligibility, and provided pre-existing health conditions protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre/post-ACA implementation. Methods Using the multicenter Childhood Cancer Survivor Study, we included participants from two cross-sectional
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Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer Cancer Cell (IF 50.3) Pub Date : 2024-05-13 Daniiar Dyikanov, Aleksandr Zaitsev, Tatiana Vasileva, Iris Wang, Arseniy A. Sokolov, Evgenii S. Bolshakov, Alena Frank, Polina Turova, Olga Golubeva, Anna Gantseva, Anna Kamysheva, Polina Shpudeiko, Ilya Krauz, Mary Abdou, Madison Chasse, Tori Conroy, Nicholas R. Merriam, Julia E. Alesse, Noel English, Boris Shpak, Michael F. Goldberg
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Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis Cancer Cell (IF 50.3) Pub Date : 2024-05-13 Tarun Gupta, Agne Antanaviciute, Chloe Hyun-Jung Lee, Rosana Ottakandathil Babu, Anna Aulicino, Zoe Christoforidou, Paulina Siejka-Zielinska, Caitlin O’Brien-Ball, Hannah Chen, David Fawkner-Corbett, Ana Sousa Geros, Esther Bridges, Colleen McGregor, Nicole Cianci, Eve Fryer, Nasullah Khalid Alham, Marta Jagielowicz, Ana Mafalda Santos, Martin Fellermeyer, Simon J. Davis, Alison Simmons
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Cancer therapy with antibodies Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-05-13 Suman Paul, Maximilian F. Konig, Drew M. Pardoll, Chetan Bettegowda, Nickolas Papadopoulos, Katharine M. Wright, Sandra B. Gabelli, Mitchell Ho, Andrea van Elsas, Shibin Zhou
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A proof-of-concept study of sequential treatment with the HDAC inhibitor vorinostat following BRAF and MEK inhibitors in BRAFV600mutated melanoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-13 Alaa Embaby, Sanne C.F.A. Huijberts, Liqin Wang, Rodrigo Leite de Oliveira, Hilde Rosing, Bastiaan Nuijen, Joyce Sanders, Ingrid Hofland, Charlaine van Steenis, Roelof J.C. Kluin, Cor Lieftink, Christopher G. Smith, Christian U. Blank, Johannes V. van Thienen, John B.A.G. Haanen, Neeltje Steeghs, Frans L. Opdam, Jos H. Beijnen, Alwin D.R. Huitema, Rene Bernards, Jan H.M. Schellens, Sofie Wilgenhof
Purpose: Development of resistance limits the clinical benefit of BRAF and MEK inhibitors (BRAFi/MEKi) in BRAFV600 mutated melanoma. It has been shown that short-term treatment (14 days) with vorinostat was able to initiate apoptosis of the resistant tumor cells. We aimed to assess the anti-tumor activity of sequential treatment with vorinostat following BRAFi/MEKi in patients with BRAFV600 melanoma
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Right ON target: a new RAS-GTP inhibitor Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-05-10 Daniela Senft
Two studies published concurrently in Nature report the development and preclinical activity of RMC-7977, a multi-selective inhibitor targeting the active, GTP-bound form of RAS.
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Multiomics-based molecular subtyping based on the commensal microbiome predicts molecular characteristics and the therapeutic response in breast cancer Mol. Cancer (IF 37.3) Pub Date : 2024-05-10 Wenxing Qin, Jia Li, Na Gao, Xiuyan Kong, Liting Guo, Yang Chen, Liang Huang, Xiaobing Chen, Feng Qi
The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared
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Unveiling a novel fusion gene enhances CAR T cell therapy for solid tumors Mol. Cancer (IF 37.3) Pub Date : 2024-05-10 Zefeng Zhou, Yongming Xia, Ruixiu Chen, Panpan Gao, Shiwei Duan
The efficacy of Adoptive Cell Transfer Therapy (ACT) in combating hematological tumors has been well-documented, yet its application to solid tumors faces formidable hurdles, chief among them being the suboptimal therapeutic response and the immunosuppressive milieu within the tumor microenvironment (TME). Recently, Garcia, J. et al. present compelling findings shedding light on potential breakthroughs
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DLL3-guided therapies in small-cell lung cancer: from antibody-drug conjugate to precision immunotherapy and radioimmunotherapy Mol. Cancer (IF 37.3) Pub Date : 2024-05-10 Po-Lan Su, Karthik Chakravarthy, Naoki Furuya, Jeremy Brownstein, Jianhua Yu, Meixiao Long, David Carbone, Zihai Li, Kai He
DLL3 acts as an inhibitory ligand that downregulates Notch signaling and is upregulated by ASCL1, a transcription factor prevalent in the small-cell lung cancer (SCLC) subtype SCLC-A. Currently, the therapeutic strategies targeting DLL3 are varied, including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies. Although rovalpituzumab
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Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma Mol. Cancer (IF 37.3) Pub Date : 2024-05-10 Pinli Yue, Fenglong Bie, Jiarun Zhu, Lin-Rui Gao, Zhendiao Zhou, Guangyu Bai, Xiaobing Wang, Ziyi Zhao, Ze-Fen Xiao, Yong Li, Aiping Zhou, Wen-Yang Liu, Yuchen Jiao, Shugeng Gao
Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two
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Autologous patient-derived exhausted nano T-cells exploit tumor immune evasion to engage an effective cancer therapy Mol. Cancer (IF 37.3) Pub Date : 2024-05-09 José L. Blaya-Cánovas, Carmen Griñán-Lisón, Isabel Blancas, Juan A. Marchal, César Ramírez-Tortosa, Araceli López-Tejada, Karim Benabdellah, Marina Cortijo-Gutiérrez, M. Victoria Cano-Cortés, Pablo Graván, Saúl A. Navarro-Marchal, Jaime Gómez-Morales, Violeta Delgado-Almenta, Jesús Calahorra, María Agudo-Lera, Amaia Sagarzazu, Carlos J. Rodríguez-González, Tania Gallart-Aragón, Christina Eich, Rosario
Active targeting by surface-modified nanoplatforms enables a more precise and elevated accumulation of nanoparticles within the tumor, thereby enhancing drug delivery and efficacy for a successful cancer treatment. However, surface functionalization involves complex procedures that increase costs and timelines, presenting challenges for clinical implementation. Biomimetic nanoparticles (BNPs) have
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Plasma versus tissue tumor mutational burden as biomarkers of durvalumab plus tremelimumab response in patients with metastatic colorectal cancer in the CO.26 trial Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-10 Jonathan M. Loree, Emma Titmuss, James T. Topham, Hagen F. Kennecke, Harriet Feilotter, Shakeel Virk, Young S. Lee, Kimberly Banks, Katie Quinn, Aly Karsan, Daniel J. Renouf, Derek J. Jonker, Dongsheng Tu, Chris J. O'Callaghan, Eric X. Chen
Purpose: Tissue derived tumor mutation burden (TMB) of ≥10 mutations/Mb is a histology agnostic biomarker for the immune checkpoint inhibitor (ICI) pembrolizumab. However, the dataset on which this was validated lacked colorectal cancers (CRCs), and there is limited evidence for immunotherapy benefit in CRC using this threshold. Patients and Methods: CO.26 was a randomized phase II study of 180 patients
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Issue Information CA: Cancer J. Clin. (IF 254.7) Pub Date : 2024-05-08
No abstract is available for this article.
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Better communication is key for quality-of-life improvement in low-income and minority patients CA: Cancer J. Clin. (IF 254.7) Pub Date : 2024-05-08 Mike Fillon
Although approximately half of patients with cancer receive symptom management and advance care planning (ACP), a new study reports that the percentage is much worse—only approximately 20%—for low-income and minority patients. The researchers note that this disparity results in not just reduced quality of life for the patients but also increased costs of care for individuals and overall. The study
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The association between menopausal hormone therapy and breast cancer remains unsettled CA: Cancer J. Clin. (IF 254.7) Pub Date : 2024-05-08 Mike Fillon
“Too often, we have patients who are told concretely—by their physicians—that HT therapy is bad—it increases your breast cancer risk; this doesn‘t account for all of the other medical benefits of HRT and quality-of-life factors that impact women during menopause.” —Ellie Proussaloglou, MD It has been more than 2 decades since the Women’s Health Initiative (WHI; https://www.whi.org/) alarmed clinicians
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Understanding the complexity of p53 in a new era of tumor suppression Cancer Cell (IF 50.3) Pub Date : 2024-05-09 Yanqing Liu, Zhenyi Su, Omid Tavana, Wei Gu
p53 was discovered 45 years ago as an SV40 large T antigen binding protein, coded by the most frequently mutated TP53 gene in human cancers. As a transcription factor, p53 is tightly regulated by a rich network of post-translational modifications to execute its diverse functions in tumor suppression. Although early studies established p53-mediated cell-cycle arrest, apoptosis, and senescence as the
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Comprehensive Bridging Radiotherapy for Limited Pre-CART Non-Hodgkin Lymphoma JAMA Oncol. (IF 28.4) Pub Date : 2024-05-09 Omran Saifi, William G. Breen, William G. Rule, Yi Lin, Javier Munoz, Mohamed A. Kharfan-Dabaja, Jennifer L. Peterson
This cohort study examines the role of comprehensive bridging radiotherapy in the setting of chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma.
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Metastatic Hormone-Sensitive Prostate Cancer and Combination Treatment Outcomes JAMA Oncol. (IF 28.4) Pub Date : 2024-05-09 Maha Hussain, Karim Fizazi, Neal D. Shore, Isabel Heidegger, Matthew R. Smith, Bertrand Tombal, Fred Saad
ImportanceMetastatic hormone-sensitive prostate cancer is currently an incurable disease. Despite a high response rate to androgen-deprivation therapy, most cases progress to castration-resistant disease, the terminal phase. This review provides a summary of the most recent evidence for current and emerging management strategies, including treatment intensification with combinations of therapies. It
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Precision Colorectal Cancer Fecal Immunological Test Screening With Fecal-Hemoglobin-Concentration–Guided Interscreening Intervals JAMA Oncol. (IF 28.4) Pub Date : 2024-05-09 Amy Ming-Fang Yen, Chen-Yang Hsu, Ting-Yu Lin, Chiu-Wen Su, Han-Mo Chiu, Tony Hsiu-Hsi Chen, Sam Li-Sheng Chen
ImportanceGiven a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb–guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy.ObjectiveTo
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Dose-Adjusted EPOCH Plus Inotuzumab Ozogamicin in Adults With Relapsed or Refractory B-Cell ALL JAMA Oncol. (IF 28.4) Pub Date : 2024-05-09 Noam E. Kopmar, Kim Quach, Ted A. Gooley, Christen H. Martino, Sindhu Cherian, Mary-Elizabeth M. Percival, Anna B. Halpern, Cristina M. Ghiuzeli, Vivian G. Oehler, Janis L. Abkowitz, Roland B. Walter, Ryan D. Cassaday
ImportanceOptions for adults with relapsed or refractory B-cell acute lymphoblastic leukemia or lymphoma (B-ALL) are limited, and new approaches are needed. Inotuzumab ozogamicin (InO) has been combined with low-intensity chemotherapy, with modest improvements over historical controls, and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) treatment is safe
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Watch and Wait for Near-Complete Responders—A Word of Caution JAMA Oncol. (IF 28.4) Pub Date : 2024-05-09 José G. Guillem, Dimitrios N. Varvoglis
This Viewpoint discusses the establishment of a cutoff point as the watch and wait approach is increasingly used in patients with locally advanced rectal cancer.
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Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis Cancer Discov. (IF 28.2) Pub Date : 2024-05-09 Santiago Demajo, Joan Enric Ramis-Zaldivar, Ferran Muinos, Miguel L. Grau, Maria Andrianova, Nuria Lopez-Bigas, Abel Gonzalez-Perez
Clonal hematopoiesis (CH) is a phenomenon of clonal expansion of hematopoietic stem cells driven by somatic mutations affecting certain genes. Recently, CH has been linked to the development of hematologic malignancies, cardiovascular diseases, and other conditions. Although the most frequently mutated CH driver genes have been identified, a systematic landscape of the mutations capable of initiating
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Biomarker identification and risk prediction model development for differentiated thyroid carcinoma lung metastasis based on primary lesion proteomics Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-09 Xiaoqi Peng, Hongbo Zhao, Lijuan Ye, Fei Hou, Zihan Yi, Yanxin Ren, Lin Lu, Fukun Chen, Juan Lv, Yinghui Wang, Haolin Cai, Xihua Zheng, Qing Yang, Ting Chen
Purpose: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. Experimental Design: Through proteomic
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Phase II Clinical Trial of Intravenous Levothyroxine to Mitigate Pharyngocutaneous Fistula in Euthyroid Patients Undergoing Salvage Laryngectomy Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-09 Molly E. Heft Neal, Catherine T. Haring, Emily Bellile, Craig C. Jaffe, Andrew G. Shuman, Steven B. Chinn, Chaz L. Stucken, Kelly M. Malloy, Keith A. Casper, Mark E.P. Prince, Douglas B. Chepeha, Andrew J. Rosko, Matthew E. Spector
Purpose: Patients undergoing head and neck cancer surgery after prior radiation or chemoradiation are at high risk for wound complications. Hypothyroidism is a known risk factor for wound complications, especially fistulae after salvage total laryngectomy. The purpose of this phase II clinical trial is to investigate the effect of peri-operative intravenous levothyroxine supplementation on wound complications
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MYC Inhibition Potentiates CD8+ T Cells Against Multiple Myeloma and Overcomes Immunomodulatory Drug Resistance Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-09 Lorraine N. Davis, Zachary J. Walker, Lauren T. Reiman, Sarah E. Parzych, Brett M. Stevens, Craig T. Jordan, Peter A. Forsberg, Daniel W. Sherbenou
Purpose: Immunomodulatory drugs (IMiDs), such as lenalidomide and pomalidomide, are cornerstone therapies in Multiple Myeloma (MM), yet patients inevitably become refractory. IMiDs exert cytotoxicity through inducing Cereblon-dependent proteasomal degradation of IKZF1 and IKZF3, resulting in downregulation of the oncogenic transcription factors IRF4 and MYC. To date, clinical IMiD resistance independent
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Safety And Efficacy Of Combination Lurbinectedin Plus Doxorubicin From A Phase 1b Trial In Patients With Advanced/Metastatic Soft Tissue Sarcoma Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-09 Gregory M. Cote, Candace L. Haddox, Edwin Choy, Priscilla A. Merriam, Emanuele Mazzola, Vinayak Venkataraman, Thierry Alcindor, Andrew J. Wagner, George D. Demetri, Suzanne George
Purpose: While cytotoxic chemotherapy is standard first-line treatment for patients with metastatic soft tissue sarcoma (STS), clinical outcomes remain suboptimal. Our prior study showed lurbinectedin plus doxorubicin is well-tolerated with promising clinical activity in STS. We designed this phase 1b trial to optimize dosing as the basis for a randomized trial in leiomyosarcoma (LMS) and to further
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The use of master protocols for efficient trial design to evaluate radiotherapy interventions: a systematic review J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-05-09 Alexandra Gilbert, Robert Samuel, Daniel Cagney, David Sebag-Montefiore, Julia Brown, Sarah R Brown
The aim of this review was to highlight why the use of master protocols trial design is particularly useful for radiotherapy intervention trials where complex-set up pathways (including quality assurance, user training, integrating multiple modalities of treatment) may hinder clinical advances. We carried out a systematic review according to PRISMA guidelines, reviewing the findings using a landscape
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Prevalence of anal cytology screening among persons with HIV and lack of access to high-resolution anoscopy at HIV care facilities J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-05-09 Sun Hee Rim, Linda Beer, Mona Saraiya, Yunfeng Tie, Xin Yuan, John Weiser
Background Persons with HIV (PWH) at highest risk of anal cancer include gay, bisexual, and other men who have sex with men (GBMSM) and transgender women aged ≥ 35 years, and other PWH aged ≥ 45 years. Identifying and treating precancerous lesions can reduce anal cancer incidence in these groups. We assessed prevalence of anal cytology and access to high-resolution anoscopy (HRA) among PWH, overall
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AACR 2024 Nat. Rev. Cancer (IF 78.5) Pub Date : 2024-05-08 Gabrielle Brewer
The annual American Association for Cancer Research (AACR) meeting provides a platform for scientists, clinicians and other stakeholders to share the latest advances in cancer science and medicine. Here, we outline some highlights of the 2024 meeting.
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Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells Mol. Cancer (IF 37.3) Pub Date : 2024-05-08 Ying Xie, Yu Huang, Zhi-Yong Li, Weihua Jiang, Nan-Xi Shi, Yuanzhi Lu, Guangchao Cao, Zhinan Yin, Xue-Jia Lin
Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry
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ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment Mol. Cancer (IF 37.3) Pub Date : 2024-05-08 Juan Zhang, Fan Ouyang, Anbo Gao, Tian Zeng, Ming Li, Hui Li, Wenchao Zhou, Qing Gao, Xing Tang, Qunfeng Zhang, Xiaomin Ran, Gang Tian, Xiyun Quan, Zhenzi Tang, Juan Zou, Yifei Zeng, Yunzhu Long, Yukun Li
The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. Liquid chromatography
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Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells Mol. Cancer (IF 37.3) Pub Date : 2024-05-08 Lisa-Marie Rieckmann, Michael Spohn, Lisa Ruff, David Agorku, Lisa Becker, Alina Borchers, Jenny Krause, Roisin O’Reilly, Jurek Hille, Janna-Lisa Velthaus-Rusik, Niklas Beumer, Armin Günther, Lena Willnow, Charles D. Imbusch, Peter Iglauer, Ronald Simon, Sören Franzenburg, Hauke Winter, Michael Thomas, Carsten Bokemeyer, Nicola Gagliani, Christian F. Krebs, Martin Sprick, Olaf Hardt, Sabine Riethdorf
Circulating tumor cells (CTCs) hold immense promise for unraveling tumor heterogeneity and understanding treatment resistance. However, conventional methods, especially in cancers like non-small cell lung cancer (NSCLC), often yield low CTC numbers, hindering comprehensive analyses. This study addresses this limitation by employing diagnostic leukapheresis (DLA) to cancer patients, enabling the screening
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D3S-001, a KRAS G12C inhibitor with rapid target engagement kinetics, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities Cancer Discov. (IF 28.2) Pub Date : 2024-05-08 Jing Zhang, Sun Min Lim, Mi Ra Yu, Cheng Chen, Jia Wang, Wenqian Wang, Haopeng Rui, Jingtao Lu, Shun Lu, Tony Mok, Zhi Jian Chen, Byoung C. Cho
First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. One potential explanation for their modest clinical activity is the dynamic “cycling” of KRAS between its GDP- and GTP-bound states, raising controversy about whether targeting the GDP-bound form can fully block this oncogenic driver. We herein report D3S-001, a next
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CDKN2A/B homozygous deletion sensitizes IDH-mutant glioma to CDK4/6 inhibition Clin. Cancer Res. (IF 11.5) Pub Date : 2024-05-08 Ali M. Nasser, Lisa Melamed, Ethan Wetzel, Chia-Chen Chang, Hiroaki Nagashima, Yosuke Kitagawa, Logan Muzyka, Hiroaki Wakimoto, Daniel P. Cahill, Julie J. Miller
Purpose: Treatment paradigms for Isocitrate dehydrogenase (IDH) mutant gliomas are rapidly evolving. While typically indolent and responsive to initial treatment, these tumors invariably recur at higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcome. We investigated the effect
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Estrogen induces LCAT to maintain cholesterol homeostasis and suppress hepatocellular carcinoma development Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Wenzhi He, Min Wang, Xuechun Zhang, Yilan Wang, Dongli Zhao, Wenhua Li, Fang Lei, Min Peng, Zhonglin Zhang, Yufeng Yuan, Zan Huang
Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified LCAT as the most highly
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HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T Cell Lymphoma Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Jiayan Zhu, Feng Wang, Lining Wang, Bo Dai, Guilin Xu, Luyao Zhao, Huimin Jiang, Wenhui Gao, Tingting Zhang, Chenxi Zhao, Yun-Xuan Li, Jiong Hu, Ke Li
Peripheral T cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Here, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3
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A Virus-Inspired Inhalable Liponanogel Induces Potent Antitumor Immunity and Regression in Metastatic Lung Tumors Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Junyao Li, Lanqing Luo, Jia He, Jinchao Yu, Xinyan Li, Xueying Shen, Junxia Zhang, Sai Li, Jeffrey M. Karp, Rui Kuai
Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy to enhance antitumor immunity by promoting type I interferon secretion. However, following pulmonary delivery, poly(I:C) suffers from rapid degradation and poor endosomal escape, thus limiting its potency. Inspired
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The Circadian Clock Component RORA Increases Immunosurveillance in Melanoma by Inhibiting PD-L1 Expression Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Dandan Liu, Benliang Wei, Long Liang, Yue Sheng, Shengjie Sun, Xing Sun, Maohua Li, Haobo Li, Chaoying Yang, Yuanliang Peng, Yifang Xie, Chengcai Wen, Lu Chen, Xionghao Liu, Xiang Chen, Hong Liu, Jing Liu
Circadian clock perturbation frequently occurs in cancer and facilitates tumor progression by regulating malignant growth and shaping the immune microenvironment. Emerging evidence has indicated that clock genes are disrupted in melanoma and linked to immune escape. Here, we found that the expression of retinoic acid receptor-related orphan receptor-α (RORA) is downregulated in melanoma patients and
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Single-cell analyses reveal the metabolic heterogeneity and plasticity of the tumor microenvironment during head and neck squamous cell carcinoma progression Cancer Res. (IF 11.2) Pub Date : 2024-05-08 Xiaoyan Meng, Yang Zheng, Lingfang Zhang, Peipei Liu, Zhonglong Liu, Yue He
Metabolic reprogramming is a hallmark of cancer. In addition to metabolic alterations in the tumor cells, multiple other metabolically active cell types in the tumor microenvironment (TME) contribute to the emergence of a tumor-specific metabolic milieu. Here, we defined the metabolic landscape of the TME during progression of head and neck squamous cell carcinoma (HNSCC) by performing single-cell
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Prostate Cancer Incidence and Mortality in Men Exposed to α1-Adrenoceptor Antagonists J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-05-08 Lars Björnebo, Shirin Razdan, Andrea Discacciati, Thorgerdur Palsdottir, Markus Aly, Tobias Nordström, Martin Eklund, Dara Lundon, Henrik Grönberg, Ash Tewari, Peter Wiklund, Natasha Kyprianou, Anna Lantz
Background α1-antagonists are commonly used to treat benign prostatic hyperplasia. Preclinical studies suggest they induce cell death and inhibit tumor growth. This study evaluates the risk of prostate cancer death in men using α1-antagonists. Methods A population-based cohort study in Stockholm, Sweden (January 1, 2007 to December 31, 2019) including 451,779 men with a prostate-specific antigen (PSA)
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Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in U.S. breast cancer survivors J. Natl. Cancer Inst. (IF 10.3) Pub Date : 2024-05-08 Jacqueline B Vo, Cody Ramin, Lene H S Veiga, Carolyn Brandt, Rochelle E Curtis, Clara Bodelon, Ana Barac, Véronique L Roger, Heather Spencer Feigelson, Diana S M Buist, Erin J Aiello Bowles, Gretchen L Gierach, Amy Berrington de González
Background Although breast cancer survivors are at risk for cardiovascular disease (CVD) from treatment late effects, evidence to inform long-term and age-specific cardiovascular surveillance recommendations is lacking. Methods We conducted a retrospective cohort study of 10,211 women diagnosed with first primary unilateral breast cancer in Kaiser Permanente Washington or Colorado (aged 20+, survived