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Perilymphatic regulatory T cell-dendritic cell interactions represent a novel axis of immunosuppression in cancer Cancer Cell (IF 48.8) Pub Date : 2024-07-18
Dendritic cells are critical inducers of adaptive anti-tumor immunity. However, their maturation, activation, and migration are often compromised in the tumor microenvironment. In this issue, You et al. demonstrate a novel axis of suppression of dendritic cell function mediated by interaction with regulatory T cells in perilymphatic niches.
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Transcription factor dependencies identify BAF-dependent cancers Cancer Cell (IF 48.8) Pub Date : 2024-07-18
In Cancer Cell, Bolomsky et al., Duplaquet et al., and He et al. identify cancers that are dependent on the BAF chromatin remodeling complex, specifically IRF4-driven multiple myeloma and POU2F3-subtype small cell lung cancer, highlighting potential therapeutic applications for BAF complex inhibitors/degraders.
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Targeting the mSWI/SNF complex in POU2F-POU2AF transcription factor-driven malignancies Cancer Cell (IF 48.8) Pub Date : 2024-07-18
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Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer Cancer Cell (IF 48.8) Pub Date : 2024-07-18
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Tumor-infiltrating lymphocytes: A new hope Cancer Cell (IF 48.8) Pub Date : 2024-07-18
Tumor-infiltrating lymphocytes (TILs) can be massively expanded from resected tumors and used as a cellular treatment for advanced malignancies. TILs require a preparative non-myeloablative chemotherapy followed by an abbreviated course of interleukin-2. Here, we review the historical development of TIL therapy and discuss potential solutions to ongoing roadblocks that may result in broader and improved
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Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity Cancer Cell (IF 48.8) Pub Date : 2024-07-18
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BCMA-directed therapy for early relapsed and/or refractory multiple myeloma Nat. Rev. Clin. Oncol. (IF 81.1) Pub Date : 2024-07-19 Niels W. C. J. van de Donk, Sonja Zweegman
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A targetable secreted neural protein drives pancreatic cancer metastatic colonization and HIF1a nuclear retention Cancer Discov. (IF 29.7) Pub Date : 2024-07-19 Norihiro Yamaguchi, Y Gloria Wu, Ethan Ravetch, Mai Takahashi, Abdul G. Khan, Akimasa Hayashi, Wenbin Mei, Dennis Hsu, Shigeaki Umeda, Elisa de Stanchina, Ivo C. Lorenz, Christine A. Iacobuzio-Donahue, Sohail F. Tavazoie
Pancreatic ductal adenocarcinoma (PDAC) is an increasingly diagnosed cancer that kills 90% of afflicted patients, with most patients receiving palliative chemotherapy. We identified neuronal pentraxin 1 (NPTX1) as a cancer secreted protein that becomes over-expressed in human and murine PDAC cells during metastatic progression and identified adhesion molecule with Ig like domain 2 (AMIGO2) as its receptor
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Phase II trial of HER-Vaxx, a B cell peptide-based vaccine, in HER2-overexpressing advanced gastric cancer patients under platinum-based chemotherapy (HERIZON) Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-19 Joshua Tobias, Marina Maglakelidze, Zoran Andrić, Dinara Ryspayeva, Iurie Bulat, Ivan Nikolić, Zoran Petrovic, Tanuj Chawla, Rajnish Nagarkar, Erika Garner-Spitzer, Christoph C. Zielinski, Leslie Mi Ok. Chong, Bonnie Nixon, Nicholas J. Ede, Sharon Yavrom, Michael Kundi, Ursula Wiedermann
Purpose: A multicenter, randomized, open-label, Phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunological efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6%-30% of gastroesophageal adenocarcinomas (GEAs). Patients and Methods: Patients (n=36) with GEA were treated with standard-of-care chemotherapy (n=17) or HER-Vaxx
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An international Multi-Institutional validation of T1 Sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-07-19 Joseph R Habib, Ingmar F Rompen, Brady A Campbell, Paul C M Andel, Benedict Kinny-Köster, Ryte Damaseviciute, D Brock Hewitt, Greg D Sacks, Ammar A Javed, Marc G Besselink, Hjalmar C van Santvoort, Lois A Daamen, Martin Loos, Jin He, I Quintus Molenaar, Markus W Büchler, Christopher L Wolfgang
Background Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared to its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated. Methods Consecutive upfront surgery patients with IPMN-derived
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The SCRUM-MONSTAR Cancer-Omics Ecosystem: Striving for a Quantum Leap in Precision Medicine Cancer Discov. (IF 29.7) Pub Date : 2024-07-18 Tadayoshi Hashimoto, Yoshiaki Nakamura, Takao Fujisawa, Mitsuho Imai, Taro Shibuki, Naoko Iida, Hiroshi Ozaki, Norio Nonomura, Chigusa Morizane, Hiroji Iwata, Susumu Okano, Wataru Yamagami, Naoya Yamazaki, Shigenori Kadowaki, Hiroya Taniguchi, Makoto Ueno, Shogen Boku, Eiji Oki, Yoshito Komatsu, Satoshi Yuki, Akitaka Makiyama, Tomoyuki Otsuka, Hiroki Hara, Naohiro Okano, Tomohiro Nishina, Yasutoshi
The SCRUM-Japan MONSTAR-SCREEN consortium is a nationwide molecular profiling project employing artificial intelligence–driven multi-omics analyses for patients with advanced malignancies, aiming to develop novel therapeutics and diagnostics and deliver effective drugs to patients. Concurrently, studies assessing molecular residual disease–based precision medicine for resectable solid tumors, including
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Neoadjuvant Exercise Therapy in Prostate Cancer JAMA Oncol. (IF 22.5) Pub Date : 2024-07-18 Lee W. Jones, Chaya S. Moskowitz, Catherine P. Lee, Gina A. Fickera, Su S. Chun, Meghan G. Michalski, Kurtis Stoeckel, Whitney P. Underwood, Jessica A. Lavery, Umeshkumar Bhanot, Irina Linkov, Chau T. Dang, Behfar Ehdaie, Vincent P. Laudone, James A. Eastham, Anne Collins, Patricia T. Sheerin, Lydia Y. Liu, Stefan E. Eng, Paul C. Boutros
ImportanceObservational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known.ObjectiveTo identify recommended phase 2 dose of exercise therapy for patients with prostate cancer.Design, Setting, and ParticipantsThis single-center, phase 1a dose-finding trial was conducted at
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Immunotherapy vs Best Supportive Care for Patients With Hepatocellular Cancer With Child-Pugh B Dysfunction JAMA Oncol. (IF 22.5) Pub Date : 2024-07-18 Claudia Angela Maria Fulgenzi, Bernhard Scheiner, Antonio D’Alessio, Aman Mehan, Giulia F. Manfredi, Ciro Celsa, Naoshi Nishida, Celina Ang, Thomas U. Marron, Linda Wu, Anwaar Saeed, Brooke Wietharn, Antonella Cammarota, Tiziana Pressiani, Matthias Pinter, Rohini Sharma, Jaekyung Cheon, Yi-Hsiang Huang, Pei-Chang Lee, Samuel Phen, Anuhya Gampa, Anjana Pillai, Andrea Napolitano, Caterina Vivaldi, Francesca
ImportanceWhether patients with Child-Pugh class B (CP-B) cancer with unresectable hepatocellular carcinoma (uHCC) benefit from active anticancer treatment vs best supportive care (BSC) is debated.ObjectiveTo evaluate the association of immune checkpoint inhibitor (ICI)–based therapies vs BSC with overall survival (OS) of patients with uHCC and CP-B liver dysfunction.Design, Setting, and ParticipantsThis
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Advancing Genomic Cancer Medicine in Rural and Underserved States JAMA Oncol. (IF 22.5) Pub Date : 2024-07-18 Jens Rueter, Edison T. Liu
This Viewpoint presents an organizational and social template for medical communities to provide contemporary care for patients with cancer in rural and underserved states.
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Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer Cancer Res. (IF 12.5) Pub Date : 2024-07-18 Alissandra L. Hillis, Timothy D. Martin, Haley E. Manchester, Jenny Högström, Na Zhang, Emmalyn Lecky, Nina Kozlova, Jonah Lee, Nicole S. Persky, David E. Root, Myles Brown, Karen Cichowski, Stephen J. Elledge, Taru Muranen, David A. Fruman, Simon T. Barry, John G. Clohessy, Ralitsa R. Madsen, Alex Toker
Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer patient deaths due to extensive molecular heterogeneity, high recurrence rates and lack of targeted therapies. Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT pathway occurs in approximately 50% of TNBC patients. Here, we performed a genome-wide CRISPR/Cas9 screen with PI3Kα and AKT inhibitors
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NAT10 Phase Separation Regulates YTHDF1 Splicing to Promote Gastric Cancer Progression Cancer Res. (IF 12.5) Pub Date : 2024-07-18 Songyi Liu, Chunlin Lin, Xiang Lin, Penghang Lin, Ruofan He, Xiaoyu Pan, Yan Lin, Jianxin Ye, Guangwei Zhu
Gastric cancer (GC) is an aggressive malignancy with poor patient outcomes. NAT10 is an acetyltransferase that has been reported to contribute to GC progression. In-depth investigation into the underlying molecular mechanisms driven by NAT10 could help identify therapeutic targets to improve GC treatment. Here, we found that NAT10 forms condensates to regulate RNA dynamics and promote GC progression
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Targeting the Sodium-Potassium Pump as a Therapeutic Strategy in Acute Myeloid Leukemia Cancer Res. (IF 12.5) Pub Date : 2024-07-18 Constanze Schneider, Hermes Spaink, Gabriela Alexe, Neekesh V. Dharia, Ashleigh Meyer, Lucy A. Merickel, Delan Khalid, Sebastian Scheich, Bjorn Haupl, Louis M. Staudt, Thomas Oellerich, Kimberly Stegmaier
Tissue-specific differences in the expression of paralog genes, which are not essential in most cell types due to the buffering effect of the partner pair, can make for highly selective gene dependencies. To identify selective paralogous targets for acute myeloid leukemia (AML), we integrated the Cancer Dependency Map with numerous datasets characterizing protein-protein interactions, paralog relationships
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CCN6 suppresses metaplastic breast carcinoma by antagonizing WNT/β-catenin signaling to inhibit EZH2-driven EMT Cancer Res. (IF 12.5) Pub Date : 2024-07-18 Maria E. Gonzalez, Bryce Brophy, Ahmad Eido, Adele E. Leonetti, Sabra I. Djomehri, Giuseppina Augimeri, Nicholas J. Carruthers, Raymond G. Cavalcante, Francesca Giordano, Sebastiano Andò, Alexey I. Nesvizhskii, Eric R. Fearon, Celina G. Kleer
Metaplastic breast carcinomas (mBrCAs) are a highly aggressive subtype of triple negative breast cancer (TNBC) with histological evidence of epithelial to mesenchymal transition (EMT) and aberrant differentiation. Inactivation of the tumor suppressor gene CCN6 (also known as WISP3) is a feature of mBrCAs, and mice with conditional inactivation of Ccn6 in mammary epithelium (Ccn6-KO) develop spindle
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Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer Cancer Res. (IF 12.5) Pub Date : 2024-07-18 Jianqiang Yang, Fanghui Chen, Liwei Lang, Fan Yang, Zhenzhen Fu, Juan Martínez, Amber Cho, Nabil F. Saba, Yong Teng
Head and neck squamous cell carcinoma (HNSCC) is addicted to glutaminolysis. Targeting this metabolic dependency has emerged as a potential therapeutic approach for HNSCC. Here, we conducted a bioinformatic analysis of the TCGA HNSCC cohort that revealed a robust correlation between expression of c-Myc and GLS1, which catalyzes the first step in glutaminolysis. Intriguingly, disruption of GLS1 signaling
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Cryoablation does not significantly contribute to systemic effector immune responses in poorly immunogenic B16F10 melanoma model Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-18 Chakradhar Yakkala, Jesus Corria-Osorio, Lana Kandalaft, Alban Denys, Bhanu Koppolu, Rafael Duran
Purpose: Cryoablation is a minimally invasive procedure implemented to destroy solid tumors. It also results in the release of tumor antigens into the systemic circulation. Pre-clinical studies employing immunogenic tumor models have shown that cryoablation evokes anti-tumor immune responses. How cryoablation impacts immune responses in poorly immunogenic tumors has not been sufficiently explored.
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Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-18 Yazi Yang, Sen Qin, Mengyu Yang, Ting Wang, Ru Feng, Chunli Zhang, Enrun Zheng, Qinghua Li, Pengyu Xiang, Shangyong Ning, Xiaodong Xu, Xin Zuo, Shuai Zhang, Xiaoya Yun, Xuehong Zhou, Yue Wang, Lin He, Yongfeng Shang, Luyang Sun, Hui Liu
Purpose: To investigate the remodeling of multiple myeloma (MM) microenvironment after BCMA-targeted chimeric antigen receptor T cell (CAR-T) therapy. Experimental Design: We performed single-cell RNA sequencing (scRNA-seq) on paired bone marrow specimens (n = 14) from 7 MM patients before (i.e., baseline, 'day −4') and after (i.e., 'day 28') post-lymphodepleted BCMA CAR-T therapy. Results: Our analysis
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The innate immune landscape of dMMR/MSI cancers predicts outcome of nivolumab treatment: results from the Drug Rediscovery Protocol Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-18 Laurien J. Zeverijn, Birgit S. Geurts, Thomas W. Battaglia, Jade M. van Berge Henegouwen, Gijs F. de Wit, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Paul Roepman, Wendy W.J. de Leng, Anne M.L. Jansen, Myriam Chalabi, Carla M.L. van Herpen, Lot A. Devriese, Frans L.G. Erdkamp, Mariette Labots, Maja J. A. de Jonge, Emile D. Kerver, Adriaan D. Bins, Lindsay V.M. Leek, Jessica C
Purpose: Treatment efficacy of nivolumab was evaluated in patients with advanced, treatment-refractory solid dMMR/MSI tumors and in-depth biomarker analyses were performed to inform precision immunotherapy approaches. Patients and methods: Patients with dMMR/MSI tumors who exhausted standard-of-care treatment options were enrolled in the Drug Rediscovery Protocol (DRUP), a pan-cancer clinical trial
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Oral and gut microbiome alterations in oral chronic graft-versus-host disease: results from Close Assessment and Testing for Chronic GVHD (CATCH study) Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Armin Rashidi, Joseph Pidala, Betty K. Hamilton, Steven Z. Pavletic, Katie Kim, Alex Zevin, Jacqueline W. Mays, Stephanie J. Lee
Purpose: Whether and how the oral microbiome and its changes in allogeneic hematopoietic cell transplantation (alloHCT) recipients may contribute to oral chronic graft-versus-host disease (cGVHD) pathogenesis is unknown. In addition, while the oral and colonic microbiota are distinct in healthy adults, whether oral microbes may ectopically colonize the gut in alloHCT patients is unknown. Experimental
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PIKing up and AKTing on resistance mutations in osimertinib-treated EGFR-mutated NSCLC Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Natalie I. Vokes, Xiuning Le, Timothy A. Yap
A recent study identified high rates of PI3K-AKT pathway mutations from the FLAURA and AURA3 osimertinib trials and pre-clinically validated that these mutations decreased osimertinib sensitivity in EGFR-mutated NSCLC. The AKT inhibitor capivasertib was found to overcome this resistance, providing important rationale for the development of AKT inhibitors in NSCLC.
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Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small-Cell Lung Cancer: The Phase II BALTIC Study Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Niels Reinmuth, Oscar Juan-Vidal, Dariusz Kowalski, Maciej Bryl, Anna Kryzhanivska, David Vicente, Zsolt Horváth, Gabriella Gálffy, Eszter Csánky, Zsolt Pápai Székely, Ihor Vynnychenko, Jon Armstrong, Tapashi Dalvi, Mingchao Xie, Sonia Iyer, Yashaswi Shrestha, Haiyi Jiang, Igor Bondarenko
Purpose: The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small-cell lung cancer (ES-SCLC). Experimental Design: Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab
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Precision oncology and systemic targeted therapy in Pseudomyxoma Peritonei Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Jordi Martínez-Quintanilla, Débora Cabot, Doménico Sabia, Oriol Arqués, Jordi Vergés, Irene Chicote, Lana Bijelic, Laia Cabellos, Anna M. Alcántara, Isabel Ramos, Pedro Barrios, Oriol Crusellas, Lina M. Palacio, Juan A. Cámara, Jorge Barriuso, Juan J. Jiménez, Pau Muñoz-Torres, Lara Nonell, Raquel Flores, Enzo Médico, Marcello Guaglio, Javier Ros, Elena Élez, Josep Tabernero, Omer Aziz, Marcello Deraco
Purpose: Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in PMP patients. New therapeutic strategies are therefore urgently needed for these
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Targeting AKR1B10 by drug repurposing with epalrestat overcomes chemoresistance in non-small cell lung cancer patient-derived tumor organoids Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Kanve N. Suvilesh, Yariswamy Manjunath, Yulia I. Nussbaum, Mohamed Gadelkarim, Murugesan Raju, Akhil Srivastava, Guangfu Li, Wesley C. Warren, Chi-Ren Shyu, Feng Gao, Matthew A. Ciorba, Jonathan B. Mitchem, Satyanarayana Rachagani, Jussuf T. Kaifi
Purpose: Systemic treatments given to non-small cell lung cancer (NSCLC) patients are often ineffective due to drug resistance. In the present study, we investigated patient-derived tumor organoids (PDTOs) and matched tumor tissues from surgically treated NSCLC patients to identify drug repurposing targets to overcome resistance towards standard-of-care platinum-based doublet chemotherapy. Experimental
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PD1/PD-L1 blockade in clear cell renal cell carcinoma: mechanistic insights, clinical efficacy, and future perspectives Mol. Cancer (IF 27.7) Pub Date : 2024-07-16 Zhaoyang Zhu, Yigang Jin, Jing Zhou, Fei Chen, Minjie Chen, Zhaofeng Gao, Lingyu Hu, Jinyan Xuan, Xiaoping Li, Zhengwei Song, Xiao Guo
The advent of PD1/PD-L1 inhibitors has significantly transformed the therapeutic landscape for clear cell renal cell carcinoma (ccRCC). This review provides an in-depth analysis of the biological functions and regulatory mechanisms of PD1 and PD-L1 in ccRCC, emphasizing their role in tumor immune evasion. We comprehensively evaluate the clinical efficacy and safety profiles of PD1/PD-L1 inhibitors
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Clinical application of liquid biopsy in colorectal cancer: detection, prediction, and treatment monitoring Mol. Cancer (IF 27.7) Pub Date : 2024-07-16 Xiang-Yuan Tao, Qian-Qian Li, Yong Zeng
Colorectal cancer (CRC) is one of the most prevalent malignancies affecting the gastrointestinal tract and is ranked third among cancers with the highest incidence and second-highest mortality rate worldwide. CRC exhibits a slow progression providing a wide treatment window. The currently employed CRC screening methods have shown great potential to prevent CRC and reduce CRC-related morbidity and mortality
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Interim Phase II Results Using Panitumumab-IRDye800CW During Transoral Robotic Surgery in Patients with Oropharyngeal Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-16 Logan D. Stone, Benjamin B. Kasten, Shilpa Rao, Manuel L. Gonzalez, Todd M. Stevens, Diana Lin, William Carroll, Benjamin Greene, Lindsay S. Moore, Andrew Fuson, Sherin James, Yolanda E. Hartman, Susan McCammon, Bharat Panuganti, Lisle M. Nabell, Yufeng Li, Mei Li, Luke Bailey, Eben L. Rosenthal, Harishanker Jeyarajan, Carissa M. Thomas, Jason M. Warram
Purpose: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence guided surgery (FGS) strategies to aid
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Risk factors for breast cancer subtypes by race and ethnicity: A scoping review J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-07-16 Amber N Hurson, Thomas U Ahearn, Hela Koka, Brittany D Jenkins, Alexandra R Harris, Sylvia Roberts, Sharon Fan, Jamirra Franklin, Gisela Butera, Renske Keeman, Audrey Y Jung, Pooja Middha, Gretchen L Gierach, Xiaohong R Yang, Jenny Chang-Claude, Rulla M Tamimi, Melissa A Troester, Elisa V Bandera, Mustapha Abubakar, Marjanka K Schmidt, Montserrat Garcia-Closas
Background Breast cancer is comprised of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated. Methods We conducted a qualitative, scoping literature review using the Preferred Reporting
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Unveiling the PDK4-centered rituximab-resistant mechanism in DLBCL: the potential of the “Smart” exosome nanoparticle therapy Mol. Cancer (IF 27.7) Pub Date : 2024-07-15 Xin Wu, Chunmei Ban, Woding Deng, Xuewei Bao, Ning Tang, Yupeng Wu, Zhixuan Deng, Jianbin Xiong, Qiangqiang Zhao
Diffuse large B-cell lymphoma (DLBCL) represents a prevalent malignant tumor, with approximately 40% of patients encountering treatment challenges or relapse attributed to rituximab resistance, primarily due to diminished or absent CD20 expression. Our prior research identified PDK4 as a key driver of rituximab resistance through its negative regulation of CD20 expression. Further investigation into
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Is There a Mathematician on Board? Cancer Res. (IF 12.5) Pub Date : 2024-07-15 Elana J. Fertig
As convergence science is emerging as a theme in cancer research, scientists from diverse backgrounds, including mathematics, are increasingly entering our research community. The captain of a Southwest Airlines flight recently paged in jest for a mathematician to help support fuel calculations that would enable a flight to arrive safely at the American Association for Cancer Research (AACR) Annual
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Earliest Metabolic Changes Associated with the Initiation of Pancreatic Cancer Cancer Res. (IF 12.5) Pub Date : 2024-07-15 Peter Storz
Pancreatic cancer is usually detected at a late stage, when tumors have already metastasized; therefore, it has a poor prognosis with a 5-year survival rate of 11% to 12%. A key to targeting this high mortality is to develop methods for detecting the disease at a stage in which it is still local to the pancreas. However, this needs a better understanding of the events that govern pancreatic cancer
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Metabolic Reprogramming Is an Initial Step in Pancreatic Carcinogenesis That Can Be Targeted to Inhibit Acinar-to-Ductal Metaplasia Cancer Res. (IF 12.5) Pub Date : 2024-07-15 Thorsten Neuß, Min-Chun Chen, Nils Wirges, Sinem Usluer, Rupert Oellinger, Svenja Lier, Michael Dudek, Tobias Madl, Martin Jastroch, Katja Steiger, Werner Schmitz, Henrik Einwächter, Roland M. Schmid
Metabolic reprogramming is a hallmark of cancer and is crucial for cancer progression, making it an attractive therapeutic target. Understanding the role of metabolic reprogramming in cancer initiation could help identify prevention strategies. To address this, we investigated metabolism during acinar-to-ductal metaplasia (ADM), the first step of pancreatic carcinogenesis. Glycolytic markers were elevated
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Spatial heterogeneity of immune regulators drives dynamic changes of local immune responses, affecting disease outcomes in pancreatic cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-15 Eva Karamitopoulou, Anna Silvia Wenning, Animesh Acharjee, Pauline Aeschbacher, Ilaria Marinoni, Inti Zlobec, Beat Gloor, Aurel Perren
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is considered a low immunogenic tumor with “cold” tumor microenvironment (TME) and is mostly unresponsive to immune checkpoint blockade therapies. Here we decipher the impact of intratumoral heterogeneity of immune determinants on antitumor response. Experimental Design: We performed spatial proteomic and transcriptomic analyses and multiplexed immunofluorescence
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NETosis Impact on Tumor Biology, Radiation, and Systemic Therapy Resistance Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-15 Yvonne M. Mowery, Jason J. Luke
NETosis via lytic neutrophil death or neutrophil activation is associated with standard cancer therapies, notably including radiotherapy, is immunosuppressive, and may enhance metastasis and treatment resistance. This emerging area of research should be prioritized in drug development and standard of care treatment paradigms including radiation, chemo- and immunotherapy.
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Associations of immune checkpoint predictive biomarkers MHC-I and MHC-II with clinical and molecular features in a diverse breast cancer cohort Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-15 Xiaopeng Sun, Laura C. Kennedy, Paula I. Gonzalez-Ericsson, Violeta Sanchez, Melinda Sanders, Charles M. Perou, Melissa A. Troester, Justin M. Balko, Sonya A. Reid
Purpose: Immunotherapy (IO) in triple negative breast cancer (TNBC) has improved survival outcomes, with promising improvements in pCR rates among early high-risk HR+/HER2- breast cancers. However, biomarkers are needed to select patients likely to benefit from IO. MHC-I and tumor-specific MHC-II (tsMHC-II) expression are candidate biomarkers for PD-(L)1 checkpoint inhibition, but existing data from
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Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States, 2019 CA: Cancer J. Clin. (IF 503.1) Pub Date : 2024-07-11 Farhad Islami, Emily C. Marlow, Blake Thomson, Marjorie L. McCullough, Harriet Rumgay, Susan M. Gapstur, Alpa V. Patel, Isabelle Soerjomataram, Ahmedin Jemal
In 2018, the authors reported estimates of the number and proportion of cancers attributable to potentially modifiable risk factors in 2014 in the United States. These data are useful for advocating for and informing cancer prevention and control. Herein, based on up-to-date relative risk and cancer occurrence data, the authors estimated the proportion and number of invasive cancer cases (excluding
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Prevalence of cancer survivors in the United States J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-07-13 Emily Tonorezos, Theresa Devasia, Angela B Mariotto, Michelle A Mollica, Lisa Gallicchio, Paige Green, Michelle Doose, Rachelle Brick, Brennan Streck, Crystal Reed, Janet S de Moor
Background With aging of the population and improvements in diagnosis, treatment, and supportive care, the number of cancer survivors in the United States has increased; updated prevalence estimates are needed. Methods Cancer prevalence on January 1, 2022, was estimated using the Prevalence Incidence Approach Model, utilizing incidence, survival, and mortality. Prevalence by age decade, sex, and time
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Circulating tumor DNA dynamics reveal KRAS G12C mutation heterogeneity and response to treatment with the KRAS G12C inhibitor divarasib in solid tumors Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Yoonha Choi, Neekesh V. Dharia, Tomi Jun, Julie Chang, Stephanie Royer-Joo, Kenneth K. Yau, Zoe June. Assaf, Junko Aimi, Smruthy Sivakumar, Meagan Montesion, Adrian Sacher, Patricia LoRusso, Jayesh Desai, Jennifer L. Schutzman, Zhen Shi
Purpose: To inform prognosis, treatment response, disease biology, and KRAS G12C mutation heterogeneity, we conducted exploratory circulating tumor DNA (ctDNA) profiling on 134 patients with solid tumors harboring a KRAS G12C mutation treated with single-agent divarasib (GDC-6036) in a phase 1 study. Experimental design: Plasma samples were collected for serial ctDNA profiling at baseline (Cycle 1
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A Phase II study assessing Long-Term Response to Ibrutinib Monotherapy in recurrent or refractory CNS Lymphoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Christian Grommes, Subhiksha Nandakumar, Lauren R. Schaff, Igor Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Jacqueline Stone, Alissa A. Thomas, Sarah S. Tang, Julia Wolfe, Alexis Bozza, Venissala Wongchai, Allison Hyde, Emma Barrett, Elizabeth A. Lynch, Juli T. Madzsar, Andrew Lin, Anna F. Piotrowski, Elena Pentsova, Jasmine H. Francis, Vaios Hatzoglou, Nikolaus Schultz, Anne S. Reiner, Katherine
Background: Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase (BTK). We previously reported the safety and short-term antitumor activity of ibrutinib in 20 patients with relapsed or refractory (r/r) primary (PCNSL) or secondary CNS lymphoma (SCNSL). Patients and Methods: We enrolled 26 additional patients with r/r PCNSL/SCNSL into the dose-expansion cohort of the trial into a combined
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CSF1R Inhibition in Patients With Advanced Solid Tumors or Tenosynovial Giant Cell Tumor: A Phase 1 Study of Vimseltinib Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Hans Gelderblom, Albiruni Abdul. Razak, Matthew H. Taylor, Todd M. Bauer, Breelyn Wilky, Javier Martín-Broto, Alejandro Falcón. Gonzalez, Piotr Rutkowski, Bartlomiej Szostakowski, Thierry Alcindor, Ramy Saleh, Sofia Genta, Silvia Stacchiotti, Michiel van de Sande, Andrew J. Wagner, Nicholas Bernthal, Lara E. Davis, Jacqueline Vuky, Christopher Tait, Bahar Matin, Supraja Narasimhan, Maitreyi G. Sharma
Purpose: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control
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Eftilagimod alpha (soluble LAG-3 protein) combined with pembrolizumab as second-line therapy for patients with metastatic head and neck squamous cell carcinoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Martin Forster, Irene Brana, Antonio Lopez Pousa, Bernard Doger, Patricia Roxburgh, Pawan Bajaj, Julio Peguero, Matthew Krebs, Enric Carcereny, Grisma Patel, Christian Mueller, Chrystelle Brignone, Frederic Triebel
Purpose: Eftilagimod alpha (efti), a soluble LAG-3 protein, activates antigen-presenting cells (APC) and downstream T-cells. TACTI-002 (Part C) evaluated whether combining efti with pembrolizumab led to strong anti-tumor responses in 2nd line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, while demonstrating good tolerability. Methods: In this multinational phase
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HER2DX Genomic Assay in HER2-positive Early Breast Cancer Treated with Trastuzumab and Pertuzumab: A Correlative Analysis from PHERGain Phase II Trial Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Antonio Llombart-Cussac, José Pérez-García, Fara Brasó-Maristany, Laia Paré, Guillermo Villacampa, Maria Gion, Peter Schmid, Marco Colleoni, Manuel Ruiz. Borrego, Patricia Galván, Joel S. Parker, Wesley Buckingham, Charles M. Perou, Patricia Villagrasa, Jose Antonio. Guerrero, Miguel Sampayo-Cordero, Mario Mancino, Aleix Prat, Javier Cortés
Purpose: To assess the predictive capability of HER2DX assay following (neo)adjuvant trastuzumab-pertuzumab (HP)-based therapy in HER2-positive (HER2+) early breast cancer (EBC). Experimental Design: HER2DX was analyzed in baseline pre-treatment tumors from PHERGain trial. Patients with stage I-IIIA HER2+ EBC were randomized to group A (docetaxel, carboplatin, and HP [TCHP]) and group B (HP ± endocrine
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Older Adults with Cancer and Common Comorbidities—Challenges and Opportunities in Improving Their Cancer Treatment Outcomes J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-07-12 Weiwei Chen, Rachel D Altshuler, Phil Daschner, Carolina Salvador Morales, Diane C St Germain, Jennifer Guida, Pataje G S Prasanna, Jeffrey C Buchsbaum
The older American population is rapidly increasing, and millions of older adults will be cancer survivors with comorbidities. This population faces specific challenges regarding treatment and has unique clinical needs. Recognizing this need, the National Cancer Institute (NCI), in collaboration with the National Institute on Aging (NIA), hosted a webinar series, entitled “Cancer, Aging, and Comorbidities
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ERBB2 amplification in gastric cancer: a genomic insight into ethnic disparities J. Natl. Cancer Inst. (IF 9.9) Pub Date : 2024-07-12 Muhammad Bilal Mirza, Jungyoon Choi, Paula Marincola Smith, Jordan J Baechle, Chandrasekhar Padmanabhan, Andreana N Holowatyj, Shailja C Shah, Xingyi Guo, Kamran Idrees
Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial and ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity
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Targeting chromosomal instability in patients with cancer Nat. Rev. Clin. Oncol. (IF 81.1) Pub Date : 2024-07-11 Duaa H. Al-Rawi, Emanuele Lettera, Jun Li, Melody DiBona, Samuel F. Bakhoum
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ESRP1-mediated biogenesis of circPTPN12 inhibits hepatocellular carcinoma progression by PDLIM2/ NF-κB pathway Mol. Cancer (IF 27.7) Pub Date : 2024-07-11 Yang Ji, Chuangye Ni, Yanjun Shen, Zhenggang Xu, Lei Tang, Fei Yu, Lingbang Zhu, Hao Lu, Chuanyong Zhang, Shikun Yang, Xuehao Wang
Emerging evidence indicates the pivotal involvement of circular RNAs (circRNAs) in cancer initiation and progression. Understanding the functions and underlying mechanisms of circRNAs in tumor development holds promise for uncovering novel diagnostic indicators and therapeutic targets. In this study, our focus was to elucidate the function and regulatory mechanism of hsa-circ-0003764 in hepatocellular
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Response-Adapted Ultralow-Dose Radiation Therapy for Orbital Indolent B-Cell Lymphoma JAMA Oncol. (IF 22.5) Pub Date : 2024-07-11 Chelsea C. Pinnix, Bouthaina S. Dabaja, Jillian R. Gunther, Penny Q. Fang, Susan Y. Wu, Loretta J. Nastoupil, Paolo Strati, Ranjit Nair, Sairah Ahmed, Raphael Steiner, Jason Westin, Sattva Neelapu, Maria A. Rodriguez, Hun Ju Lee, Michael Wang, Christopher Flowers, Lei Feng, Bita Esmaeli
ImportanceRadiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common.ObjectiveTo determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity.Design, Setting, and ParticipantsThis single-institution, phase 2 prospective nonrandomized
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Initial Management of BRAF V600E-Variant Anaplastic Thyroid Cancer JAMA Oncol. (IF 22.5) Pub Date : 2024-07-11 Sarah Hamidi, Ramona Dadu, Mark E. Zafereo, Renata Ferrarotto, Jennifer R. Wang, Anastasios Maniakas, G. Brandon Gunn, Anna Lee, Michael T. Spiotto, Priyanka C. Iyer, Luana G. Sousa, Neal S. Akhave, Salmaan Ahmed, Kim O. Learned, Charles Lu, Stephen Y. Lai, Michelle Williams, S. Mohsen Hosseini, Naifa L. Busaidy, Maria E. Cabanillas
ImportanceBRAF/MEK inhibitors revolutionized the treatment of BRAF V600E-variant anaplastic thyroid carcinoma (BRAFv-ATC), offering improved outcomes for patients with this previously incurable disease.ObservationsAnaplastic thyroid carcinoma (ATC) accounts for approximately half of thyroid cancer−related deaths. It presents as a rapidly growing tumor that often invades locoregional structures and
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Waterpipe Tobacco Smoking and Risk of Cancer Mortality JAMA Oncol. (IF 22.5) Pub Date : 2024-07-11 Ngoan Tran Le, Can Van Phan, Yen Thi-Hai Pham, Phuoc Hong Le, Hang Viet Dao, Long Cong Nguyen, Jian-Min Yuan, Hung N. Luu
ImportanceThere has been an increasing trend of using noncigarette products, including waterpipe tobacco (WTP), worldwide. While cigarette smoking is a well-established risk factor for numerous cancers, little is known about the association between WTP smoking and cancer mortality.ObjectiveTo assess the association between WTP smoking and risk of cancer mortality in Vietnam.Design, Setting, and ParticipantsThis
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Measurable Residual Disease and Clinical Outcomes in Chronic Lymphocytic Leukemia JAMA Oncol. (IF 22.5) Pub Date : 2024-07-11 Fausto Alfredo Rios-Olais, Alyssa K. McGary, Mazie Tsang, Diana Almader-Douglas, Jose F. Leis, Matthew R. Buras, Talal Hilal
ImportanceMeasurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role
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Ionizable STING-Activating Nanoadjuvants Enhance Tumor Immunogenicity and Potentiate Immunotherapy Efficacy in Solid Tumors Cancer Res. (IF 12.5) Pub Date : 2024-07-11 Shiyun Xian, Xiaona Chen, Sihang Ren, Xiaolong Chen, Hangxiang Wang
Therapeutic strategies that induce inflammatory responses in immunologically “cold” tumors have the potential to improve immunotherapeutic outcomes. Pharmacologically activating the STING pathway induces innate immunity, subsequently enhancing tumor immunogenicity. Here, we developed a nanoadjuvant with tumor-restricted pharmacology that rapidly activated STING and reshaped the tumor microenvironment
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Hypoxic Memory Mediates Prolonged Tumor Intrinsic Type I Interferon Suppression to Promote Breast Cancer Progression Cancer Res. (IF 12.5) Pub Date : 2024-07-11 Oihana Iriondo, Desirea Mecenas, Yilin Li, Christopher R. Chin, Amal Thomas, Aidan Moriarty, Rebecca Marker, Yiru Jess. Wang, Haley Hendrick, Yonatan Amzaleg, Veronica Ortiz, Matthew MacKay, Amber Dickerson, Grace Lee, Sevana Harotoonian, Bérénice A. Benayoun, Andrew Smith, Christopher E. Mason, Evanthia T. Roussos Torres, Remi Klotz, Min Yu
Hypoxia is a common feature of many solid tumors due to aberrant proliferation and angiogenesis that is associated with tumor progression and metastasis. Most of the well-known hypoxia effects are mediated through hypoxia-inducible factors (HIFs). Identification of the long-lasting effects of hypoxia beyond the immediate HIF-induced alterations could provide a better understanding of hypoxia-driven
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An Atlas of Accessible Chromatin in Advanced Prostate Cancer Reveals the Epigenetic Evolution during Tumor Progression Cancer Res. (IF 12.5) Pub Date : 2024-07-11 Raunak Shrestha, Lisa N. Chesner, Meng Zhang, Stanley Zhou, Adam Foye, Arian Lundberg, Alana S. Weinstein, Martin Sjöström, Xiaolin Zhu, Thaidy Moreno-Rodriguez, Haolong Li, SU2C/PCF West Coast Prostate Cancer Dream Team, Joshi J. Alumkal, Rahul Aggarwal, Eric J. Small, Mathieu Lupien, David A. Quigley, Felix Y. Feng
Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that resists therapy targeting androgen signaling, the primary driver of prostate cancer. mCRPC resists androgen receptor (AR) inhibitors by amplifying AR signaling or by evolving into therapy-resistant subtypes that do not depend on AR. Elucidation of the epigenetic underpinnings of these subtypes could provide important insights
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Increased PVR Expression on Bone Marrow Macrophages May Promote Resistance to TIGIT Blockade in Multiple Myeloma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-11 Ester Lozano, Mari-Pau Mena, Glòria Garrabou, Oriol Cardus, Tania Díaz, David F. Moreno, Joan Mañé Pujol, Aina Oliver-Caldés, Anthony Battram, Natalia Tovar, Maria Teresa Cibeira, Luis Gerardo Rodríguez-Lobato, Joan Bladé, Carlos Fernández de Larrea, Laura Rosinol
Purpose: TIGIT blockade in our ex vivo models of bone marrow (BM) reduced the number of malignant plasma cells (PCs) in only half of patients with multiple myeloma (MM). Here we wanted to investigate whether increased expression of TIGIT ligands may inhibit T cell immune response promoting resistance to TIGIT blockade. Experimental Design: We first characterized the number and phenotype of BM macrophages
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Differences in the prognostic role of age, extent of resection and tumor grade between astrocytoma IDHmt and oligodendroglioma: a single center cohort study Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-11 Thijs van der Vaart, Maarten M.J. Wijnenga, Karin van Garderen, Hendrikus Jan Dubbink, Pim J. French, Marion Smits, Clemens M.F. Dirven, Johan M. Kros, Arnaud J.P.E. Vincent, Martin J. van den Bent
Purpose: IDH-mutant glioma are classified as oligodendroglioma or astrocytoma on the basis of 1p19q-codeletion. Whether prognostic factors are similar between these tumor types is not well understood. Experimental Design: Retrospective cohort study. Molecular characterization was performed with targeted next-generation sequencing. Tumor volumes were calculated using semi-automatic 3D segmentation on
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Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration Resistant Prostate Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-11 Christopher J. Sweeney, Russell Petry, Chang Xu, Merrida Childress, Jie He, David Fabrizio, Ole Gjoerup, Samantha Morley, Timothy Catlett, Zoe June. Assaf, Kobe Yuen, Matthew Wongchenko, Kalpit Shah, Pratyush Gupta, Priti Hegde, Lincoln W. Pasquina, Sanjeev Mariathasan, Ryon P. Graf, Thomas Powles
Purpose: Enzalutamide after abiraterone progression is commonly used in metastatic castration resistant prostate cancer (mCRPC) despite a low rate of clinical benefit. Analyzing IMbassador250, a phase III trial assessing enzalutamide with or without atezolizumab after abiraterone, we hypothesized that baseline and early changes in circulating tumor DNA (ctDNA) tumor fraction (TF) may identify patients
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Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer Mol. Cancer (IF 27.7) Pub Date : 2024-07-10 Claudia Cifuentes, Clara L. Oeste, Isabel Fernández-Pisonero, Alejandro M. Hortal, Carmen García-Macías, Jeanne Hochart, Regina Rubira, Lydia Horndler, Carlos Horndler, Xosé R. Bustelo, Balbino Alarcón
Breast cancer (BC) is the most common cancer in women, with triple negative BC (TNBC) accounting for 20% of cases. While early detection and targeted therapies have improved overall life expectancy, TNBC remains resistant to current treatments. Although parity reduces the lifetime risk of developing BC, pregnancy increases the risk of developing TNBC for years after childbirth. Although numerous gene