tbuckley/cabot-search huggingface dataset:
The Far Side of Resistance to RAS Inhibitors
Authors: Michelangelo Marasco, Sandra Misale
Journal: Cancer Discovery (2024)

Summary: In this issue, four articles highlight the critical role of nongenetic mechanisms and cell plasticity in mediating resistance to different classes of RAS inhibitors in pancreatic ductal adenocarcinoma and non–small cell lung cancer. See related article by Benitz et al., p. 2162 See related article by Dilly et al., p. 2135 See related article by Araujo et al., p. 2183 See related article by Singhal et al., p. 2122
Highlighted Research Articles
Journal: Blood Cancer Discovery (2024)

In This Issue| November 01 2024 Highlighted Research Articles Author & Article Information Online ISSN: 2643-3249 Print ISSN: 2643-3230 ©2024 American Association for Cancer Research2024American Association for Cancer Research Blood Cancer Discov (2024) 5 (6): 374. https://doi.org/10.1158/2643-3230.BCD-5-6-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record November 1 2024 Citation Highlighted Research Articles. Blood Cancer Discov 1 November 2024; 5 (6): 374. https://doi.org/10.1158/2643-3230.BCD-5-6-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search By screening more than 200 drugs active in a variety of diseases, Scuoppo and colleagues have identified inhibitors of nicotinamide phosphoribosyl-transferase (NAMPTi) as active in a subset of diffuse large B-cell lymphoma (DLBCL) cases. The study also identifies a biological marker (the ratio between NAMPT and PARP1 RNA levels) that predicts sensitivity to NAMPTi. The same marker indicates higher anti-tumor activity in DLBCL cases carrying chromosomal translocations involving the BCL2 anti-apoptotic gene. Furthermore, pharmacologic inhibition of BCL2 is potently synergistic with NAMPT inhibition. These results provide a rationale for clinical trials testing the efficacy of NAMPT inhibitors in DLBCL cases with BCL2 translocation. See article, p. 417. Family history of myeloma and genetic ancestry are known contributors to myeloma risk, but this predisposition has not been pinned to specific genes. Thibaud and colleagues analyzed 1,681 germline exome sequences across two independent cohorts, discovering a pathogenic germline variant (PGV) in... You do not currently have access to this content.
Building an Organ-Wide Macroscopic View of Cancer Hallmarks
Authors: Suling Liu, Yuan Wang, Jiawen Feng, Zhihua Liu, Shengtao Zhou
Journal: Cancer Discovery (2024)

Summary: Despite an increasingly detailed understanding of cancer hallmarks at molecular or atomic resolution, most studies, however, fall short of investigating the systemic interactions of cancer with the human body. We propose to investigate the hallmarks of cancer from an organ-wide macroscopic view, discuss the challenges in preclinical and clinical research to study the cross-organ regulation of cancer together with potential directions to overcome these challenges, and foresee how this holistic view may be translated into more effective therapies.
Drugging p53: Barriers, Criteria, and Prospects
Authors: Huaxin Song, Shujun Xiao, Jiaqi Wu, Min Lu
Journal: Cancer Discovery (2024)

Summary: Pharmacologically targeting tumor suppressors necessitates an unprecedented strategy of restoring, rather than conventionally inhibiting, protein function, and p53, the most commonly mutated protein in cancer, has thus remained undruggable. In this study, we address long-standing misconceptions in the field and gaps in the scientific logic for a p53 function–restoration strategy, identify four barriers for drugging mutant p53, and accordingly propose effectiveness evaluation criteria, clinical-translating norms, and prospects for mutant p53 rescue compounds.
Redefining the Gastric Microbes in Promoting Gastric Tumorigenesis: The Rise of the Non–<i>H. pylori</i> Microbiome
Authors: Chi Chun Wong, Jun Yu
Journal: Cancer Discovery (2024)

Summary: Gastric cancer remains one of the top cancers in China compared with Western countries, mainly attributed to the high rates of Helicobacter pylori infection. However, recent discoveries on the non–H. pylori gastric microbiome have led to a paradigm shift in our understanding of microbial risk factors driving gastric cancer, which will impact future screening and prevention strategies.
A Call for Innovative Translational and Clinical Research to Address China’s Unique Cancer Landscape
Authors: Chaoqi Zhang, Peng Wu, Dongyu Li, Xuanyu Gu, Chuqi Lin, Junhan Zhou, Dexin Shang, Jingjing Liu, Ruijie Ma, Bohui Zhao, Nan Sun, Jie He
Journal: Cancer Discovery (2024)

Summary: The Chinese government has, in recent decades, implemented various administrative laws and regulatory policies to expedite cancer therapeutic development, boosting research and development pipelines for domestic pharmaceutical companies and clinical trials; however, China faces unique challenges given the high prevalence of certain cancer types and distinct disease burdens, some of which are frequently overlooked by international pharmaceutical companies. Given the substantial unmet need for China-specific cancer care, it is crucial to promote the development of innovative pharmaceutical and clinical research in China, with a particular emphasis on addressing tumors most prevalent in its population.
Combination Diagnostics: Adding Blood-Based ctDNA Screening to Low-Dose CT Imaging for Early Detection of Lung Cancer
Authors: Daniel A. Haber, Steven J. Skates
Journal: Cancer Discovery (2024)

Summary: Annual low-dose CT screening of individuals with a smoking history identifies early curable lung tumors and reduces cancer mortality by 20%, yet only a minority of eligible patients undergo such monitoring. Mazzone and colleagues apply a blood-based cfDNA fragmentomic assay as a high-sensitivity/low-specificity pre-screen to help stratify individuals who may benefit most from more definitive low-dose CT imaging. See related article by Mazzone et al., p. 2224
Exploring the Interplay of Diet, Obesity, Immune Function, and Cancer
Authors: Yumin Fu, Xinyu Guo, Linmao Sun, Tianming Cui, Jiabei Wang, Yao Liu, Lianxin Liu
Journal: Cancer Discovery (2024)

Summary: This commentary provides an in-depth exploration of the intricate relationships among diet, obesity, immune function, and cancer, highlighting the potential role of dietary interventions as complementary therapies in cancer treatment. Multiple analyses underscore the importance of personalized dietary strategies in cancer management and identify opportunities for further research in this evolving field.
Beneath the Surface: Neoantigens beyond Chromosomal DNA Mutations
Authors: Shicheng Su
Journal: Cancer Discovery (2024)

Summary: The conventional wisdom is that the overwhelming majority of neoantigens arise from chromosomal DNA mutations; however, recent studies show that posttranscriptional and posttranslational events can also generate neoantigens. This commentary provides an overview of known and potential sources of nonchromosomal neoantigens, emerging technologies, and clinical trials that may move this field forward to redefine immunologically “hot/cold” tumors and develop next-generation immunotherapeutic approaches.
Highly Multiplexed Tissue Imaging in Precision Oncology and Translational Cancer Research
Authors: Alina Bollhagen, Bernd Bodenmiller
Journal: Cancer Discovery (2024)

Abstract Precision oncology tailors treatment strategies to a patient’s molecular and health data. Despite the essential clinical value of current diagnostic methods, hematoxylin and eosin morphology, immunohistochemistry, and gene panel sequencing offer an incomplete characterization. In contrast, highly multiplexed tissue imaging allows spatial analysis of dozens of markers at single-cell resolution enabling analysis of complex tumor ecosystems; thereby it has the potential to advance our understanding of cancer biology and supports drug development, biomarker discovery, and patient stratification. We describe available highly multiplexed imaging modalities, discuss their advantages and disadvantages for clinical use, and potential paths to implement these into clinical practice. Significance: This review provides guidance on how high-resolution, multiplexed tissue imaging of patient samples can be integrated into clinical workflows. It systematically compares existing and emerging technologies and outlines potential applications in the field of precision oncology, thereby bridging the ever-evolving landscape of cancer research with practical implementation possibilities of highly multiplexed tissue imaging into routine clinical practice.
The American Psychiatric Association Practice Guideline for the Treatment of Patients With Borderline Personality Disorder
Authors: George A. Keepers, Laura J. Fochtmann, Joan M. Anzia, Sheldon Benjamin, Jeffrey M. Lyness, Ramin Mojtabai, Mark Servis, Lois Choi-Kain, Kaz J. Nelson, John M. Oldham, Carla Sharp, Amanda Degenhardt, Laura J. Fochtmann, John M. Oldham, Seung-Hee Hong, Jennifer Medicus
Journal: American Journal of Psychiatry (2024)
Early Cancer Detection Through Comprehensive Mapping of Dynamic Tumorigenesis
Authors: Jiang Chang, Tongsen Zheng, Chen Wu
Journal: Cancer Discovery (2024)

Summary: Current strategies for early cancer detection and diagnosis need updating to achieve greater precision, necessitating the creation of a comprehensive evolutionary map of tumorigenesis. This requires establishing high-quality prospective cohorts, systematically collecting samples for integrated spatiotemporal multiomics analyses, and efficiently translating laboratory findings into clinical applications.
Disparities in Treatment for Alcohol Use Disorder Among All of Us Participants
Authors: Phuc Le, Jacob James Rich, Eden Y. Bernstein, Joseph Glass, Hamlet Gasoyan, Sudie E. Back, Thanh C. Bui, None Gina Ayers, Michael B. Rothberg
Journal: American Journal of Psychiatry (2024)

The authors examined racial/ethnic and socioeconomic disparities in receiving treatment for alcohol use disorder (AUD).
Advancing Cancer Prevention through an AI-Based Integration of Traditional and Western Medicine
Authors: Peng Zhang, Qian Zhang, Shao Li
Journal: Cancer Discovery (2024)

Summary: Traditional Chinese medicine has accumulated a wealth of experiences in individualized cancer prevention and serves as a complement to Western medicine. We propose an artificial intelligence–based integration of traditional and Western medicine as a new paradigm for cancer prevention, encompassing cancer risk screening and preventive intervention, which will provide new solutions for cancer prevention and offer fresh perspectives for traditional medicine research worldwide.
Highlighted research articles
Journal: Cancer Discovery (2024)

In This Issue| November 01 2024 Highlighted research articles Author & Article Information Online ISSN: 2159-8290 Print ISSN: 2159-8274 ©2024 American Association for Cancer Research2024American Association for Cancer Research Cancer Discov (2024) 14 (11): 2015–2017. https://doi.org/10.1158/2159-8290.CD-14-11-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record November 1 2024 Citation Highlighted research articles. Cancer Discov 1 November 2024; 14 (11): 2015–2017. https://doi.org/10.1158/2159-8290.CD-14-11-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Chimeric antigen receptors (CAR) enable MHC-independence but do not recreate the precise molecular regulation induced by T-cell receptor (TCR) complexes. In an effort to engage endogenous TCR circuits, Chang and colleagues designed MHC-independent TCRs. Using predictive modeling, they found many biochemical and structural conflicts at the synthetic hybrid domain interface. Through iterative modeling and sequence modification, they "evolved" these receptors towards native-like structures, yielding significantly enhanced function across several models of cancer. Combination with 4-1BB costimulation enabled robust tumor control that was more durable than classic second-generation CARs. These observations pave a path for structure-informed design of novel antigen receptors. See article, p. 2109. Targeting oncogenic KRAS, the primary driver of pancreas cancer, holds promise, but responses are limited by acquired resistance. Singhal and colleagues found that acute resistance to KRAS inhibition is driven by a classical cell state, marked by highly differentiated, epithelial features. Genetic tools in mouse... You do not currently have access to this content.
Immunogenicity and Efficacy of Personalized Adjuvant mRNA Cancer Vaccines
Authors: Pedro Berraondo, Raquel Cuesta, Miguel F. Sanmamed, Ignacio Melero
Journal: Cancer Discovery (2024)

Summary: In this issue, Gainor and colleagues report on the immunogenicity of personalized neoantigen-encoding mRNA vaccines that elicit measurable polyfunctional CD8+ and CD4+ T-cell responses in patients whose tumors have been resected. Reactivity is substantiated to 20% to 30% of the predicted MHC-I and MHC-II epitopes in four patients with NSCLC postsurgically treated with the vaccine alone and in 12 patients with melanoma treated with their individualized vaccines plus pembrolizumab in the context of a phase 1 clinical trial (NCT03313778). See related article by Gainor et al., p. 2209
A pathophysiologic framework for the overlap of disorders of gut-brain interaction and the role of the gut microbiome
Authors: Ayesha Shah, Yeong Yeh Lee, Hidekazu Suzuki, Joash Tan-Loh, Kewin Tien Ho Siah, Kok-Ann Gwee, Thomas Fairlie, Nicholas J. Talley, Uday C Ghoshal, Yen-Po Wang, Yong Sung Kim, Gerald Holtmann
Journal: Gut Microbes (2024)

The International Rome Committee defines Disorders of Gut-Brain Interactions (DGBI) based upon distinct combinations of chronic and/or recurrent unexplained gastrointestinal symptoms. Yet patients often experience overlapping DGBI. Patients with DGBI frequently also suffer from extraintestinal symptoms, including fatigue, sleep disturbances, anxiety, and depression. Patients with overlapping DGBI typically experience more severe GI symptoms and increased psychosocial burden. Concerning the pathophysiology, DGBI are associated with disruptions in gut motility, function of the brain and enteric neurons, immune function, and genetic markers, with recent findings revealing gut microbiome alterations linked to these mechanisms of DGBI. Emerging evidence summarized in this review suggests that the microbiome influences various established disease mechanisms of different DGBI groups. Overall, changes in the gastrointestinal microbiome do not seem to be linked to a specific DGBI subgroup but may play a key role in the manifestation of different DGBI and, subsequently, overlap of DGBI. Understanding these shared mechanisms and the role of the gastrointestinal microbiome, particularly for overlapping DGBI, might aid in developing more precise diagnostic criteria and treatment strategies while developing personalized interventions that target specific mechanisms to improve patient outcomes.
Raman spectroscopy on dried blood plasma allows diagnosis and monitoring of colorectal cancer
Authors: Carlo Morasso, Elena Daveri, Arianna Bonizzi, Marta Truffi, Francesco Colombo, Piergiorgio Danelli, Sara Albasini, Licia Rivoltini, Serena Mazzucchelli, Luca Sorrentino, Fabio Corsi
Journal: MedComm (2024)

Abstract Colorectal cancer (CRC) remains challenging to diagnose, necessitating the identification of a noninvasive biomarker that can differentiate it from other conditions such as inflammatory bowel diseases (IBD) and diverticular disease (DD). Raman spectroscopy (RS) stands out as a promising technique for monitoring blood biochemical profiles, with the potential to identify distinct signatures identifying CRC subjects. We performed RS analysis on dried plasma from 120 subjects: 32 CRC patients, 37 IBD patients, 20 DD patients, and 31 healthy controls. We also conducted longitudinal studies of CRC patient's postsurgery to monitor the spectral changes over time. We identified six spectral features that showed significant differences between CRC and non‐CRC patients, corresponding to tryptophan, tyrosine, phenylalanine, lipids, carotenoids, and disulfide bridges. These features enabled the classification of CRC patients with an accuracy of 87.5%. Moreover, longitudinal analysis revealed that the spectral differences normalized over 6 months after surgery, indicating their association with the presence of the disease. Our study demonstrates the potential of RS to identify specific biomolecular signatures related to CRC. These results suggest that RS could be a novel screening and monitoring tool, providing valuable insights for the development of noninvasive and accurate diagnostic methods for CRC.
Targeting the DNA damage response in cancer
Authors: Guffanti Federica, Chiappa Michela, Damia Giovanna
Journal: MedComm (2024)

DNA damage response (DDR) pathway is the coordinated cellular network dealing with the identification, signaling, and repair of DNA damage. It tightly regulates cell cycle progression and promotes DNA repair to minimize DNA damage to daughter cells. Key proteins involved in DDR are frequently mutated/inactivated in human cancers and promote genomic instability, a recognized hallmark of cancer. Besides being an intrinsic property of tumors, DDR also represents a unique therapeutic opportunity. Indeed, inhibition of DDR is expected to delay repair, causing persistent unrepaired breaks, to interfere with cell cycle progression, and to sensitize cancer cells to several DNA-damaging agents, such as radiotherapy and chemotherapy. In addition, DDR defects in cancer cells have been shown to render these cells more dependent on the remaining pathways, which could be targeted very specifically (synthetic lethal approach). Research over the past two decades has led to the synthesis and testing of hundreds of small inhibitors against key DDR proteins, some of which have shown antitumor activity in human cancers. In parallel, the search for synthetic lethality interaction is broadening the use of DDR inhibitors. In this review, we discuss the state-of-art of ataxia-telangiectasia mutated, ataxia-telangiectasia-and-Rad3-related protein, checkpoint kinase 1, Wee1 and Polθ inhibitors, highlighting the results obtained in the ongoing clinical trials both in monotherapy and in combination with chemotherapy and radiotherapy.
Disorganized thalamic subregional functional connectivity in bipolar I disorder
Authors: Xipeng Long, Xiuli Wang, Yuan Cao, Di Kong, Baolin Wu, Hongsheng Xie, Ziru Zhao, Neil Roberts, Qiyong Gong, Zhiyun Jia
Journal: MedComm (2024)

Abstract Thalamus plays a pivotal role in the pathophysiology of neuropsychiatric conditions due to its strategic position and intricate connectivity with the cerebral cortex, limbic system, and other subcortical structures. In the present study, the potential involvement of the thalamus and subregions of the thalamus are explored in bipolar disorder (BD). In particular, functional and structural magnetic resonance imaging was performed on 73 adult patients with BD‐I and 78 healthy controls (HCs). Seed‐based thalamus and thalamic subregional functional connectivity (FC) were compared between the BD‐I patients and HCs. Compared to HCs, patients with BD‐I showed higher FC between the left thalamus and right lingual gyrus and altered FC between the dorsal thalamus and the default mode network and prefrontal regions, which may be correlated with mania symptomatology. In patients with BD‐I, the anterior subregions of the thalamus had higher FC than the posterior subregions. No significant difference in gray matter volume or local functional activity was found in the thalamus and thalamic subregions between BD‐I and HC. These findings provide evidence of disorganized thalamocortical FC in BD‐I, suggesting that the thalamus and its subregions may play important and specific roles in the neural circuitry of BD.
Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk
Authors: Hua‐Yang Fan, Xin‐Hua Liang, Ya‐Ling Tang
Journal: MedComm (2024)

Abstract Cancer neuroscience is an emerging field that investigates the intricate relationship between the nervous system and cancer, gaining increasing recognition for its importance. The central nervous system governs the development of the nervous system and directly affects brain tumors, and the peripheral nervous system (PNS) shapes the tumor microenvironment (TME) of peripheral tumors. Both systems are crucial in cancer initiation and progression, with recent studies revealing a more intricate role of the PNS within the TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating a bidirectional interaction between nerves and cancers. Notably, immune cells also contribute to this communication, forming a triangular relationship that influences protumor inflammation and the effectiveness of immunotherapy. This review delves into the intricate mechanisms connecting the PNS and tumors, focusing on how various immune cell types influence nerve‒tumor interactions, emphasizing the clinical relevance of nerve‒tumor and nerve‒immune dynamics. By deepening our understanding of the interplay between nerves, cancer, and immune cells, this review has the potential to reshape tumor biology insights, inspire innovative therapies, and improve clinical outcomes for cancer patients.
Prognostic role of lipoprotein(a) in atherosclerotic cardiovascular disease risk from a perspective on current risk stratification
Authors: Sha Li, Hui‐Hui Liu, Yan Zhang, Meng Zhang, Hui‐Wen Zhang, Cheng‐Gang Zhu, Na‐Qiong Wu, Rui‐Xia Xu, Qian Dong, Jie Qian, Ke‐Fei Dou, Yuan‐Lin Guo, Jian‐Jun Li
Journal: MedComm (2024)

Lipoprotein(a) [Lp(a)] is an emerging predictor for atherosclerotic cardiovascular disease (ASCVD) but the association from a perspective on current risk stratification was unknown. A cohort of 9944 Chinese patients with ASCVD was recruited and refined into very-high-risk (VHR) and non-VHR subgroups according to current guideline. Lp(a) plasma levels were divided by its concentration (<30, 30-50, 50-75, and ≥75 mg/dL) and percentile zones (<25th, 25-50th, 50-75th, 75-90th, ≥90th). Cardiovascular events (CVEs) occurred during an average of 38.5 months' follow-up were recorded. We found that Lp(a) was increased with risk stratification of ASCVD increasing. Prevalence of CVEs had a significantly increasing trend with gradients of Lp(a) elevation in VHR but not in non-VHR subgroup. The adjusted HRs (95%CIs) for CVEs were 1.75(1.25-2.46) in the highest group of Lp(a) ≥75 mg/dL compared with the group of Lp(a) <30 mg/dL as the reference in overall patients, 2.18(1.32-3.58) in VHR subgroup and 1.43(0.93-2.18) in non-VHR subgroup, respectively. The adjusted HRs (95%CIs) at the highest grade of Lp(a) levels (≥90th) were 1.72(1.19-2.50) in overall population, 2.83(1.53-5.24) in VHR subgroup and 1.38(0.86-2.12) in non-VHR subgroup, respectively. These findings suggested that Lp(a) might contribute more to CVEs risk in VHR subgroup of ASCVD.