Review
Biochemistry & Molecular Biology
Ni Made Pitri Susanti, Daryono Hadi Tjahjono
Summary: The cell cycle is crucial in cell development, and its progression is controlled by endogenous CDK inhibitors, CDKs, and cyclins. Dysregulation of the cell cycle can lead to cancer, making CDK a natural target for anticancer therapy. Understanding CDK structures and complexes with drugs helps in developing CDK inhibitors, from non-selective to selective CDK4/CDK6 inhibitors applied in clinical cancer treatment.
Article
Biochemistry & Molecular Biology
Prasenjit Mondal, Saswat Mohapatra, Debmalya Bhunia, Prabir Kumar Gharai, Nabanita Mukherjee, Varsha Gupta, Satyajit Ghosh, Surajit Ghosh
Summary: Cell proliferation is a crucial step that may lead to cancer if not properly regulated, with p16 protein often remaining inactive in cancer cells. Researchers have focused on restoring the activity of p16 protein using new viral vectors, small molecules, and peptides to control abnormal cell proliferation. By conjugating a nuclear-localized signal (NLS) sequence and a short peptide (AVPI), the efficiency of p16 peptide as an anti-leukemia therapeutic agent has been significantly enhanced.
RSC MEDICINAL CHEMISTRY
(2022)
Review
Cell Biology
Rustem Uzbekov, Claude Prigent
Summary: All living organisms are composed of cells, which undergo cell division to reproduce and form a whole organism. Cell division is a highly regulated process that follows a sequence of events known as the cell cycle. The universality of the cell cycle is attributed to the shared genetic information encoded by the DNA double helix in all organisms.
Review
Oncology
Xiao-Ru Liang, Yan-Fei Liu, Feng Chen, Zhi-Xia Zhou, Li-Jie Zhang, Zhi-Juan Lin
Summary: Long non-coding RNAs (lncRNAs) are involved in various biological processes and regulate key proteins in the cell cycle of cancer cells. Understanding their role in cell cycle regulation can lead to new therapeutic strategies for cancer treatment. This review article summarizes recent studies on lncRNA control of cell cycle-related proteins and discusses their emerging role in cancer diagnosis and therapy.
CANCER MANAGEMENT AND RESEARCH
(2023)
Article
Oncology
Jing Xu, Lei Liu, Ranran Ma, Yawen Wang, Xu Chen, Haiting Liu, Youxin Ji, Tiantian Liu, Peng Gao
Summary: This study revealed that elevated KIF26A expression in breast cancer tissues is associated with lymph node metastasis. KIF26A promotes cell proliferation and cell cycle progression in breast cancer cells. The core promotor region of human KIF26A gene is located at position -395 to -385, upstream of the transcription start site. The transcriptional factor E2F1 activates KIF26A expression, leading to cell cycle progression through the CDK-RB-E2Fs pathway.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Rosa-Maria Ferraiuolo, Bre-Anne Fifield, Caroline Hamm, Lisa A. Porter
Summary: Understanding the relationship between protein expression level and response to treatment is crucial for developing novel treatment options for breast cancer patients. The data shows a correlation between Spy1 and c-Myc protein levels in more aggressive breast cancer cells and patient samples. Additionally, targeting Spy1 may confer an advantage to current chemotherapies, even when c-Myc levels are elevated.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Review
Oncology
Liguo Wang, Zhouli Yang, Guangchen Li, Yongbo Liu, Chao Ai, Yu Rao
Summary: This article summarizes the latest developments in CDK and cyclin protein degraders, covering their selectivity, application, validation, and the current state of development for CDK members lacking degraders. It provides a comprehensive overview for researchers in this field.
FRONTIERS OF MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Qingyi Hu, Tao Huang
Summary: Cyclin-dependent kinases (CDKs) play multiple regulatory roles in cell division. Abnormal cell cycle and uncontrolled proliferation are characteristic of cancer. Inhibitors targeting CDK activity have been developed and clinical trials for selective CDK4/6 inhibition have shown promising results in cancer treatment. Non-coding RNAs (ncRNAs), which do not code for proteins, have been found to be involved in cell cycle regulation and their abnormal expression has been linked to cancer. Studies have shown that ncRNAs can influence the efficacy of CDK4/6 inhibition, making them potential predictors and therapeutic candidates for cancer treatment and diagnosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Sadia Perveen, Hanfa Ashfaq, Saira Ambreen, Isbah Ashfaq, Zakia Kanwal, Asima Tayyeb
Summary: Citrullus colocynthis extracts show significant anticancer activity in human breast cancer cells by regulating cyclin-CDK inhibitors to induce cell cycle arrest. Further research on therapeutic interventions is warranted.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Toshiya Fujisaki, Ken Saito, Toshiaki Kikuchi, Eisaku Kondo
Summary: OGFOD1 is an important factor that regulates the transcription and stabilization of cell cycle-related genes, and plays a role in maintaining the function of specific cell cycle regulators during cancer cell proliferation.
Review
Oncology
Mengna Zhang, Lingxian Zhang, Ruoxuan Hei, Xiao Li, Haonan Cai, Xuan Wu, Qiping Zheng, Cheguo Cai
Summary: Dysregulated cell division is a key feature of cancer, and blocking cell division through CDK inhibitors (CDKIs) shows potential for cancer treatment. CDK4/6 inhibitors have been approved for metastatic breast cancer, but first-generation pan-CDK inhibitors have not been widely approved due to non-selectivity and toxicity. Efforts are being made to enable pan-CDK inhibitors for clinical application and combination therapy strategies have been developed to reduce toxicity and side effects.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ada Nowosad, Arnaud Besson
Summary: Lysosomes, initially known for their degradative functions, have emerged as signaling hubs that regulate various cellular processes and play a role in stem cell fate regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Mitra Zabihi, Ramin Lotfi, Amir-Mohammad Yousefi, Davood Bashash
Summary: CDKs, cyclins, and CKIs play important roles in the cell cycle regulatory machinery, and dysregulation of their expression or function can contribute to tumorigenesis. While designing CDK inhibitors to target tumor cells shows promise, the non-canonical functions of CDKs pose challenges in their application. This review aims to explore the biology of CDKs and their contribution to tumorigenesis, and discuss the pros and cons of CDK inhibition in the treatment of human cancers.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Plant Sciences
Aline Kohn Carneiro, Patricia da Fonseca Montessoro, Adriana Flores Fusaro, Bruna Gino Araujo, Adriana Silva Hemerly
Summary: In the face of climate change, plants have developed mechanisms to adapt by regulating cell division, with CDKs playing a crucial role in controlling the cell cycle. Understanding the roles of CDKs in responding to environmental stresses may be essential for increasing agricultural productivity in a changing climate.
Review
Pharmacology & Pharmacy
Oana-Maria Thoma, Markus F. Neurath, Maximilian J. Waldner
Summary: CDKs play a key role in cell cycle regulation, with aberrant expression potentially leading to cancer development. CDK inhibitors, such as CDK4/6 inhibitors, are being investigated as novel cancer therapies.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Immunology
Lucillia Bezu, Oliver Kepp, Guido Kroemer
Summary: Intratumoral injection of oncolytic agents or local administration of non-viral oncolytic therapies can activate an anticancer immune response, while local anesthetics injected into malignant lesions also possess antineoplastic effects. Combining local anesthetics with immune checkpoint inhibition can significantly improve overall survival. The molecular and cellular mechanisms underlying the combination therapy's efficacy are summarized.
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Article
Hospitality, Leisure, Sport & Tourism
Yan Qiu, Benjamin Fernandez-Garcia, H. Immo Lehmann, Li Guoping, Guido Kroemer, Carlos Lopez-Otin, Xiao Junjie
Summary: Exercise plays an active role in improving physical fitness and sustaining health. It has been widely accepted as a preventative and therapeutic strategy for various diseases. Exercise maintains and restores homeostasis at multiple levels to stimulate positive physiological adaptations that protect against pathological conditions.
JOURNAL OF SPORT AND HEALTH SCIENCE
(2023)
Article
Nutrition & Dietetics
Norbert J. Tripolt, Sebastian J. Hofer, Peter N. Pferschy, Faisal Aziz, Sylvere Durand, Fanny Aprahamian, Nitharsshini Nirmalathasan, Mara Waltenstorfer, Tobias Eisenberg, Anna M. A. Obermayer, Regina Riedl, Harald Kojzar, Othmar Moser, Caren Sourij, Heiko Bugger, Abderrahim Oulhaj, Thomas R. Pieber, Matthias Zanker, Guido Kroemer, Frank Madeo, Harald Sourij
Summary: The effects of fasting on glucose metabolism were examined in non-obese and obese participants and people with type 2 diabetes. The results showed that after 36 hours of fasting, glucose, insulin, and C-peptide levels were significantly decreased. Non-obese participants had higher glucose levels but lower insulin levels after 36 hours of fasting, while no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 hours of fasting. Metabolomics analysis revealed subtle baseline differences and attenuated metabolic response to fasting in obese participants and people with diabetes.
Review
Cell Biology
Lucille Ferret, Karla Alvarez-Valadez, Jennifer Riviere, Alexandra Muller, Natalia Bohalova, Luo Yu, Lionel Guittat, Vaclav Brazda, Guido Kroemer, Jean-Louis Mergny, Mojgan Djavaheri-Mergny
Summary: Guanine-quadruplex structures (G4) are formed by guanine-rich DNA and RNA sequences and control gene expression mechanisms. G4 ligands have been developed for potential therapeutic applications in human diseases. Recent evidence suggests that G4 ligands may target cellular components such as lysosomes and mitochondria.
Article
Sport Sciences
Layale Youssef, Sylvere Durand, Fanny Aprahamian, Deborah Lefevre, Melanie Bourgin, Maria Chiara Maiuri, Maude Dulac, Guy Hajj-Boutros, Vincent Marcangeli, Fanny Buckinx, Eva Peyrusque, Jose A. Morais, Pierrette Gaudreau, Gilles Gouspillou, Guido Kroemer, Mylene Aubertin-Leheudre, Philippe Noirez
Summary: Physical activity and nutrition are important for preventing adverse health outcomes in aging. This study investigated the effects of high-intensity interval training (HIIT) combined with citrulline (CIT) supplementation on serum metabolites in obese older adults. Results showed significant changes in 44 metabolites after the 12-week intervention, with 10 of them more affected by HIIT combined with CIT. Decreased triglycerides and aspartic acid were correlated with reduced adiposity-related parameters. Arginine, triglycerides, and aspartic acid may serve as biomarkers for cardiometabolic health and adiposity.
EUROPEAN JOURNAL OF SPORT SCIENCE
(2023)
Editorial Material
Immunology
Laurence Zitvogel, Guido Kroemer
SEMINARS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Julia Kaellberg, Alexandra Harrison, Valerie March, Santa Berzina, Ivan Nemazanyy, Oliver Kepp, Guido Kroemer, Sophie Mouillet-Richard, Pierre Laurent-Puig, Valerie Taly, Wenjin Xiao
Summary: The high mortality rate in colorectal cancer (CRC) is mainly due to drug resistance caused by intratumor heterogeneity (ITH). This study investigated the interaction between different molecular subtypes of CRC cells and found that coculturing CMS1 and CMS4 cells increased their resistance to the chemotherapeutic agent 5-fluorouracil (5-FU) and promoted cellular invasion. The secretome of CMS1 cells played a protective role for CMS4 cells against 5-FU treatment and mediated the transfer of metabolites between CMS1 and CMS4 cells.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Jing Zhang, Christina Trojel-Hansen, Jianghuang Wang, Zili Zhang, Xing Wang, Yuhui Qiao, Huike Jiao, Mickael Michaud, Oliver Kepp, Marja Jäättelä, Guido Kroemer, Qing Zhong
Summary: An experimental inducer of TNF-independent necrosis, NC1, kills human cancer cells in a non-apoptotic, necrotic manner. The cell death induced by NC1 is not inhibited by apoptosis-related pathways, but depends on reactive oxygen species (ROS) production by mitochondria and elimination of mitochondrial DNA. These findings suggest that inducing regulated necrosis may be a promising approach for anticancer therapy.
CELL DEATH & DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Melanie Bourgin, Sylvere Durand, Guido Kroemer
Summary: Multiple studies have investigated the impact of SARS-CoV-2 infection and COVID-19 severity on various metabolomes to identify diagnostic and prognostic biomarkers. The literature lacks consensus on the utility of metabolomic analyses for COVID-19 management, hence necessitating a critical assessment. Comparing mass spectrometric metabolomic studies on specimens from SARS-CoV2-infected patients, this study aims to identify relevant biomarkers by analyzing clinical design, technical aspects, and statistical analyses. Several metabolites in the plasma of COVID-19 patients may contribute to excessive inflammatory reactions and deficient immune control, revealing significant connections between whole-body metabolism and disease progression. Overall, mass spectrometric approaches show great potential for biomarker discovery if methodological standardization is implemented.
Editorial Material
Cardiac & Cardiovascular Systems
Mahmoud Abdellatif, Lea Montegut, Guido Kroemer
EUROPEAN HEART JOURNAL
(2023)
Review
Oncology
Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A. Wargo, Nicola Segata, Laurence Zitvogel
Summary: Many studies have identified Gut OncoMicrobiome Signatures (GOMS) as biomarkers for predicting immune-checkpoint inhibitor (ICI) efficacy. There is an association between oncogenesis and intestinal dysbiosis, and GOMS are shared between patients with various cancer subtypes and individuals with chronic inflammatory disorders. This review discusses these patterns, presents findings from a meta-analysis of GOMS associated with clinical benefit from ICIs, and proposes practical guidelines for incorporating GOMS in decision-making in immuno-oncology.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Review
Urology & Nephrology
Anne-Gaelle Goubet, Mathieu Rouanne, Lisa Derosa, Guido Kroemer, Laurence Zitvogel
Summary: The clinical management of advanced malignancies of the upper and lower urinary tract has been revolutionized with the advent of immune checkpoint blockers (ICBs). Bacteria infecting urothelium could be a prominent target for triggering antitumour immune responses. The authors discuss the influence of urinary tract infections on kidney and bladder cancer immunosurveillance and consider the urobiome and the effects of antibiotics.
NATURE REVIEWS UROLOGY
(2023)
Editorial Material
Oncology
Oliver Kepp, Peng Liu, Guido Kroemer, Lorenzo Galluzzi
Summary: BCL2 robustly maintains mitochondrial integrity, inhibits immune signaling and cell death, and limits the ability of dendritic cells to initiate adaptive immune responses, suggesting a universal immunosuppressive function for the mitochondrial immune checkpoint.
Editorial Material
Oncology
Marine Fidelle, Ai-Ling Tian, Laurence Zitvogel, Guido Kroemer
Summary: In a recent paper published in Science, Fidelle et al. reveal a gut immune checkpoint that is disrupted by antibiotic treatment. The dysbiosis in the ileum after antibiotic treatment leads to an increase in bile acids, which downregulates MAdCAM-1, resulting in the migration of immunosuppressive T cells from gut-associated lymphoid tissues towards tumors.
Editorial Material
Oncology
Marine Fidelle, Isabelle Lebhar, Laurence Zitvogel, Guido Kroemer
Summary: In a recent paper published in Nature, Park et al. propose a mechanism by which intestinal dysbiosis can affect the effectiveness of immunotherapy targeting the PD-L1/PD-1 interaction. Dysbiosis may increase the expression of PD-L2, which interacts with RGMb. Antibodies targeting PD-L2/RGMb have the potential to restore the response to PD-1 blockade in the context of dysbiosis.
