Review
Oncology
Douglas Hanahan
Summary: The concept of the hallmarks of cancer is a tool for simplifying the complexity of cancer phenotypes and genotypes into basic principles. This article proposes phenotypic plasticity and disrupted differentiation as distinct hallmark capabilities, and discusses nonmutational epigenetic reprogramming and polymorphic microbiomes as enabling characteristics. Additionally, the importance of senescent cells in the tumor microenvironment is highlighted. The integrative concept of the hallmarks of cancer helps in understanding the mechanisms of cancer development and applying that knowledge to cancer medicine.
Article
Multidisciplinary Sciences
Renda Li, Zhenlin Yang, Fei Shao, Hong Cheng, Yaru Wen, Sijin Sun, Wei Guo, Zitong Li, Fan Zhang, Liyan Xue, Nan Bi, Jie Wang, Yingli Sun, Yin Li, Fengwei Tan, Qi Xue, Shugeng Gao, Susheng Shi, Yibo Gao, Jie He
Summary: Primary small cell carcinoma of the esophagus (PSCCE) shares genetic similarities with esophageal squamous cell carcinoma (ESCC) but has distinct genomic alterations, transcriptome features, and molecular subtyping similar to small cell lung cancer (SCLC). RB1 disruptions are frequent in PSCCE cases. This study provides insights into potential therapeutic strategies for treating PSCCE.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Arianna Orsini, Chiara Diquigiovanni, Elena Bonora
Summary: Breast cancer (BC) is the most common diagnosed cancer type in the world, with approximately 2.26 million new cases and nearly 685,000 deaths worldwide in the last two years. BC is a complex ecosystem formed by the tumor microenvironment and malignant cells, and its heterogeneity affects treatment response. Recent advancements in high-throughput sequencing have enabled the use of various omics techniques, such as liquid biopsy, transcriptomics, epigenomics, proteomics, metabolomics, pharmaco-omics, and artificial intelligence imaging, to better understand the formation and evolution of BC. This comprehensive review focuses on the applications of multi-omics-based research in BC, including different phenotypes, biomarkers, target therapies, diagnosis, treatment, and prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ziyang Liu, Anqiang Wang, Yingying Pu, Zhongwu Li, Ruidong Xue, Chong Zhang, Xiao Xiang, E. Jian-Yu, Zhaode Bu, Fan Bai, Jiafu Ji
Summary: Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer with high mortality rate. Research suggests that HAS may originate from pluripotent precursor cells and has high stemness and methionine cycle activity. Genes involved in the methionine cycle, such as MAT2A and AHCY, are potential targets for HAS treatment.
Article
Cell Biology
Yayun Gu, Yan Zhou, Sihan Ju, Xiaofei Liu, Zicheng Zhang, Jia Guo, Jimiao Gao, Jie Zang, Hao Sun, Qi Chen, Jinghan Wang, Jiani Xu, Yiqun Xu, Yingjia Chen, Yueshuai Guo, Juncheng Dai, Hongxia Ma, Cheng Wang, Guangfu Jin, Chaojun Li, Yankai Xia, Hongbing Shen, Yang Yang, Xuejiang Guo, Zhibin Hu
Summary: In this study, the authors investigated the development and maturation of the heart by analyzing the phosphoproteome, proteome, metabolome, and transcriptome of mice hearts. They identified mitogen-activated protein kinases as core kinases involved in transcriptional regulation during early cardiogenesis. Furthermore, they discovered a network of transcription factors controlling early cardiogenesis, as well as cardiac resident macrophages clearing injured cardiomyocytes after birth. This comprehensive multi-omics data provides valuable insights into cardiac development and maturation.
Review
Cell Biology
Wan-Chen Hsieh, Bugi Ratno Budiarto, Yi-Fu Wang, Chih-Yu Lin, Mao-Chun Gwo, Dorothy Kazuno So, Yi-Shiuan Tzeng, Shih-Yu Chen
Summary: Single-cell technologies have provided insights into the heterogeneity of tumor-immune microenvironments and identified potential biomarkers, but lack spatial information. Spatial multi-omics technologies have recently been used to combine different methods and obtain markers of cancer progression.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Deshen Pan, Deshui Jia
Summary: Tumor heterogeneity, a hallmark of cancer, can impair therapy efficacy and drive tumor progression. Recent advancements in single-cell technologies have provided unprecedented resolution in uncovering intra-tumoral heterogeneity, accelerating cancer research progress. Understanding molecular mechanisms driving cancer cell plasticity is crucial for developing precision therapies.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cell Biology
Dagan Segal, Hanieh Mazloom-Farsibaf, Bo-Jui Chang, Philippe Roudot, Divya Rajendran, Stephan Daetwyler, Reto Fiolka, Mikako Warren, James F. Amatruda, Gaudenz Danuser
Summary: This study presents a quantitative high-resolution imaging assay to investigate the functional adaptation of cancer cells to different cell-extrinsic cues and molecular interventions in zebrafish xenografts. The analysis reveals systematic shifts in the distribution of cancer cell morphotypes as influenced by the tissue microenvironment. The reduced expression of an oncogene product causes changes in cell morphology and tissue specificity.
JOURNAL OF CELL BIOLOGY
(2022)
Review
Gastroenterology & Hepatology
Markus H. Frank, Brian J. Wilson, Jason S. Gold, Natasha Y. Frank
Summary: The concept of cancer stem cells (CSCs) suggests a hierarchy within tumors where a minority of more primitive cells give rise to more differentiated cells that make up the tumor bulk, but are not capable of perpetuating tumors on their own. CSCs may drive therapeutic resistance and cancer progression, and their identification and isolation methods have been established. Single-cell omics technologies offer opportunities to discover novel molecular pathways for CRC eradication.
Article
Oncology
Dean Nehama, Alex S. Woodell, Spencer M. Maingi, Shawn D. Hingtgen, Gianpietro Dotti
Summary: Glioblastoma (GBM) is a highly aggressive tumor with limited treatment options. Despite advances in understanding its molecular and immune characteristics, GBM remains resistant to targeted therapies. Cellular therapies, such as immunotherapies and stem cell-based therapies, offer potential solutions to overcome GBM's challenges. This review article focuses on evaluating the utility of these cellular therapies, categorizing them based on specificity and analyzing preclinical and clinical data to guide future development.
Review
Cell Biology
Jiexi Li, Xingdi Ma, Deepavali Chakravarti, Shabnam Shalapour, Ronald A. DePinho
Summary: Colorectal cancer ranks as the third most common cancer in women, the fourth most common in men, and the fourth leading cause of cancer death globally. Incidence and mortality rates vary by race and ethnicity, with non-Hispanic blacks having the highest rates. In recent years, there has been a decline in the incidence of colorectal cancer in individuals over 50 years old.
GENES & DEVELOPMENT
(2021)
Article
Oncology
Junyu Li, Lin Li, Peimeng You, Yiping Wei, Bin Xu
Summary: Esophageal cancer is a highly heterogeneous malignancy, characterized by cellular, genetic, and phenotypic heterogeneity. This heterogeneity affects various aspects of the cancer progression. Although heterogeneity poses challenges in treatment, it also presents opportunities for new therapeutic strategies. Artificial intelligence, particularly machine learning and deep learning algorithms, can effectively analyze multi-omics data and contribute to precision oncology in esophageal cancer. This review focuses on the use of artificial intelligence in integrating multi-omics data and discusses novel techniques such as single-cell sequencing and spatial transcriptomics for understanding tumor heterogeneity.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Christina Plattner, Giorgia Lamberti, Peter Blattmann, Alexander Kirchmair, Dietmar Rieder, Zuzana Loncova, Gregor Sturm, Stefan Scheidl, Marieke Ijsselsteijn, Georgios Fotakis, Asma Noureen, Rebecca Lisandrelli, Nina Boeck, Niloofar Nemati, Anne Krogsdam, Sophia Daum, Francesca Finotello, Antonios Somarakis, Alexander Schafer, Doris Wilflingseder, Miguel Gonzalez Acera, Dietmar Oefner, Lukas A. Huber, Hans Clevers, Christoph Becker, Henner F. Farin, Florian R. Greten, Ruedi Aebersold, Noel F. C. C. de Miranda, Zlatko Trajanoski
Summary: Precision oncology approaches for colorectal cancer patients are not as advanced as for other solid cancers. Functional precision oncology, based on perturbing primary tumor cells, could be a personalized treatment strategy. By measuring proteome activity landscapes using patient-derived organoids, we found that kinase inhibitors could have patient-specific off-target effects and pathway crosstalk. Additionally, we observed non-genetic heterogeneity of the organoids and upregulation of stemness and differentiation genes by kinase inhibitors. Imaging mass-cytometry-based profiling of primary tumors revealed information about the tumor microenvironment and tumor-immune cell interactions.
Article
Oncology
Zeynep B. Zengin, Caroline Weipert, Nicholas J. Salgia, Nazli Dizman, Joann Hsu, Luis Meza, Alexander Chehrazi-Raffle, Ramya Muddasani, Sabrina Salgia, Jasnoor Malhotra, Neal Chawla, Errol J. Philip, Lesli Kiedrowski, Benjamin L. Maughan, Nityam Rathi, Divyam Goel, Toni K. Choueiri, Neeraj Agarwal, Sumanta K. Pal
Summary: This study explores the role of circulating cell-free tumor DNA as an adjunct to tissue genomic profiling in metastic renal cell carcinoma (mRCC), confirming the feasibility and potential of using ctDNA to identify actionable alterations. The study also reveals that ctDNA and tissue-based genomic profiling are complementary, with unique alterations identified by both platforms, and the frequency of unique alterations increases with greater temporal separation between tests.
CLINICAL CANCER RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Deepavali Chakravarti, Kyle A. LaBella, Ronald A. DePinho
Summary: The escalating social and economic burden of an aging world population has brought aging research into the spotlight. Through the lens of telomere biology, we can better understand the mechanisms of aging and the development of age-related diseases, providing insights for prevention and treatment.
Article
Multidisciplinary Sciences
B. Acharya, J. Alexandre, P. Benes, B. Bergmann, S. Bertolucci, A. Bevan, H. Branzas, P. Burian, M. Campbell, Y. M. Cho, M. de Montigny, A. De Roeck, J. R. Ellis, M. El Sawy, M. Fairbairn, D. Felea, M. Frank, O. Gould, J. Hays, A. M. Hirt, D. L-J Ho, P. Q. Hung, J. Janecek, M. Kalliokoski, A. Korzenev, D. H. Lacarrere, C. Leroy, G. Levi, A. Lionti, A. Maulik, A. Margiotta, N. Mauri, N. E. Mavromatos, P. Mermod, L. Millward, V. A. Mitsou, I Ostrovskiy, P-P Ouimet, J. Papavassiliou, B. Parker, L. Patrizii, G. E. Pavalas, J. L. Pinfold, L. A. Popa, V Popa, M. Pozzato, S. Pospisil, A. Rajantie, R. Ruiz de Austri, Z. Sahnoun, M. Sakellariadou, A. Santra, S. Sarkar, G. Semenoff, A. Shaa, G. Sirri, K. Sliwa, R. Soluk, M. Spurio, M. Staelens, M. Suk, M. Tenti, V Togo, J. A. Tuszyn'ski, A. Upreti, V. Vento, O. Vives
Summary: Magnetic monopoles, hypothetical fundamental particles, are searched for via the Schwinger mechanism in lead-lead heavy ion collisions. The MoEDAL experiment used trapping detectors and SQUID magnetometers to exclude the existence of magnetic monopoles with specific masses and charges.
Review
Pharmacology & Pharmacy
Matthew T. J. Halma, Jack A. Tuszynski, Gijs J. L. Wuite
Summary: The time and cost of developing new therapeutic drugs is a significant burden, involving computational screening, compound assays, and expensive clinical trials. This review highlights the value of dynamic conformational information obtained through optical tweezers for targeting "undruggable" proteins. Optical tweezers provide insights into the relationship between biological mechanisms and structural conformations, aiding in drug discovery. Developing workflows and tools for optical tweezers will improve efficiency, allowing for greater adoption in the biopharmaceutical industry. As a complementary tool, optical tweezers increase the number of potential drug candidates, enhance understanding of a target's complex structural dynamics, and elucidate compound-target interactions.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Physical
Nasim Anousheh, Azar Shamloo, Seifollah Jalili, Jack A. Tuszynski
Summary: Understanding the behavior of confined electrolyte solutions in graphene-based channels is important for various scientific applications. In this study, molecular dynamics simulations were used to investigate the adsorption of NaCl electrolyte solutions in graphene, hexagonal boron nitride, and combined graphene-hexagonal boron nitride nano-channels. The study reveals the advantageous adsorption of sodium and chloride ions in the graphene-hexagonal boron nitride-graphene structure.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Oncology
Irene Donato, Kiran K. Velpula, Andrew J. Tsung, Jack A. Tuszynski, Consolato M. Sergi
Summary: This study proposes a mathematical and computational approach to diagnose neuroblastoma by calculating image entropy, fractal dimension, and lacunarity. The method is able to automatically predict tumor malignancy and may challenge the current classification of neuroblastoma.
Article
Chemistry, Multidisciplinary
Aarat P. Kalra, Alfy Benny, Sophie M. Travis, Eric A. . Zizzi, Austin Morales-Sanchez, Daniel G. Oblinsky, Travis J. A. . Craddock, Stuart R. Hameroff, M. Bruce MacIver, Jack A. . Tuszynski, Sabine Petry, Roger Penrose, Gregory D. Scholes
Summary: The repeating arrangement of tubulin dimers in microtubules provides great mechanical strength and allows for energy transfer. By studying tryptophan autofluorescence lifetimes, it was discovered that energy can diffuse over 6.6 nm in microtubules, and this diffusion is influenced by tubulin polymerization state but not by the average number of protofilaments. The presence of anesthetics also affects exciton diffusion.
ACS CENTRAL SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Oluwakemi Ebenezer, Pietro Comoglio, Gane Ka-Shu Wong, Jack A. Tuszynski
Summary: In the past two decades, the introduction of synthetic siRNAs into the cytoplasm has been found to effectively silence targeted genes, impacting gene expression and regulation. Extensive investments have been made in developing RNA therapeutics, including for diseases related to PCSK9. PCSK9 plays a crucial role in LDL-C uptake, and loss-of-function modifications of PCSK9 have shown significant clinical importance in reducing cholesterol levels and lowering the risk of CVD. Monoclonal antibodies and siRNA drugs targeting PCSK9 offer a promising option for managing lipid disorders and improving CVD outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Aarat P. Kalra, Somnath Biswas, Imani Mulrain, Michelle Wang, Jack A. Tuszynski, Gregory D. Scholes
Summary: Microtubules and actin filaments are protein polymers that have various energy conversion roles in cells. While their mechanochemical roles are well studied, their capabilities for photonic energy conversion are not well understood. This Perspective discusses the photophysical properties of protein polymers, the challenges and opportunities of integrating protein biochemistry with photophysics, and the potential of microtubules and actin filaments to serve as targets for photobiomodulation. It also presents the broad challenges and questions in the field of protein biophotonics, emphasizing the importance of understanding how protein polymers interact with light for biohybrid device fabrication and light-based therapeutics.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Oncology
Paola Vottero, Qian Wang, Marek Michalak, Maral Aminpour, Jack Adam Tuszynski
Summary: This study aims to identify the binding sites and modes of gatastatin and its derivatives through molecular docking simulations, and compare the computational binding free energy predictions with experimental results. The computational simulations did not show a strong preference for gamma tubulin, suggesting that further derivatization may be needed to increase its specificity.
Review
Plant Sciences
Sarah Adel, Nicolas Carels
Summary: Environmental stresses, such as drought, have a negative impact on crop yield, especially in critical regions. In light of the increasing global population and the potential effects of climate change on food supply, there is a continuous effort to understand molecular processes that can improve drought tolerance in strategic crops. This review summarizes the achievements and potential of various techniques, such as QTL mapping, genomics, epigenetics, and transgenics, for the selective breeding of drought-tolerant wheat cultivars. The combination of synthetic apomixis and the msh1 mutation shows promise in inducing and stabilizing epigenomes, which could accelerate selective breeding for drought tolerance in arid and semi-arid regions.
Article
Biochemistry & Molecular Biology
Edward A. Rietman, Hava T. Siegelmann, Giannoula Lakka Klement, Jack A. Tuszynski
Summary: The identification of a target protein for inhibition interaction is crucial for successful cancer therapy. This paper proposes a modified topological-thermodynamic analysis method that focuses on selecting the most stable proteins and their subnetwork interaction partners with high expression levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Correction
Chemistry, Physical
Aarat P. Kalra, Somnath Biswas, Imani Mulrain, Michelle Wang, Jack A. Tuszynski, Gregory D. Scholes
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Review
Nutrition & Dietetics
Matthew T. J. Halma, Jack A. Tuszynski, Paul E. Marik
Summary: Cancer can be targeted metabolically through dietary and lifestyle changes, depriving cancer cells of glucose, and utilizing nutritional supplements and repurposed drugs, which can contribute to the prevention and treatment of cancer.
Article
Biochemistry & Molecular Biology
Paola Vottero, Scott Tavernini, Alessandro D. Santin, David E. Scheim, Jack A. Tuszynski, Maral Aminpour
Summary: Hypercoagulability and formation of microclots are characteristic of acute COVID-19 and long COVID. This study investigated the potential of the antiparasitic drug ivermectin (IVM) to prevent the binding of the spike protein (SP) from SARS-CoV-2 to fibrinogen and reduce microclot formation. Computational results suggest that IVM may interfere with SP-fibrinogen binding and decrease the formation of resistant fibrin clots. Further in vitro studies are needed to validate these findings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Nicolas Carels, Domenico Sgariglia, Marcos Guilherme Vieira Jr, Carlyle Ribeiro Lima, Flavia Raquel Goncalves Carneiro, Gilberto Ferreira da Silva, Fabricio Alves Barbosa da Silva, Rafaela Scardini, Jack Adam Tuszynski, Cecilia Vianna de Andrade, Ana Carolina Monteiro, Marcel Guimaraes Martins, Talita Goulart da Silva, Helen Ferraz, Priscilla Vanessa Finotelli, Tiago Albertini Balbino, Jose Carlos Pinto
Summary: This study proposes a strategy for the development of neoplastic disease therapy based on the vulnerability of scale-free networks to specific attacks. It suggests selecting connectivity hubs in the tumors interactome as targets for personalized therapy and utilizing drug repurposing, RNA silencing, and other approaches to improve therapeutic outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Giovanna Traina, Jack A. Tuszynski
Summary: This review provides an overview of the role that classical neurotransmitters play in the contextual conditioning model of fear and PTSD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
