Reprogramming of glucose metabolism: The hallmark of malignant transformation and target for advanced diagnostics and treatments DOI Open Access
Qing Tang,

Siqi Wu,

Baiming Zhao

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117257 - 117257

Published: Aug. 12, 2024

Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly reprogramming glucose metabolism, also known as "Warburg effect". The is considered a novel hallmark human cancers. A growing number studies have shown that can regulate many biological processes cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize major functions, clinical significance, potential targets signaling pathways metabolic in Moreover, applications natural products small molecule inhibitors targeting are analyzed, some agents trial statuses summarized, well pros cons for therapy analyzed. Overall, plays an important role prediction, prevention, diagnosis treatment Glucose reprogramming-related great to serve biomarkers improving individual outcomes prognosis patients. innovations related will be hotspot research future. We suggest more high-quality trials with abundant formulations toxicology experiments would beneficial development application drugs metabolism.This review provide researchers broader perspective comprehensive understanding about significance

Language: Английский

KRAS mutation: from undruggable to druggable in cancer DOI Creative Commons

Lamei Huang,

Zhixing Guo, Fang Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 15, 2021

Abstract Cancer is the leading cause of death worldwide, and its treatment outcomes have been dramatically revolutionised by targeted therapies. As most frequently mutated oncogene, Kirsten rat sarcoma viral oncogene homologue (KRAS) has attracted substantial attention. The understanding KRAS constantly being updated numerous studies on in initiation progression cancer diseases. However, deemed a challenging therapeutic target, even “undruggable”, after drug-targeting efforts over past four decades. Recently, there surprising advances directly drugs for KRAS, especially (G12C) inhibitors, such as AMG510 (sotorasib) MRTX849 (adagrasib), which obtained encouraging results clinical trials. Excitingly, was first to be approved use this year. This review summarises recent fundamental aspects relationship between mutations tumour immune evasion, new progress targeting particularly (G12C). Moreover, possible mechanisms resistance inhibitors combination therapies are summarised, with view providing best regimen individualised achieving truly precise treatment.

Language: Английский

Citations

606
Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution DOI Creative Commons
Dian Yang, Matthew G. Jones,

Santiago Naranjo

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(11), P. 1905 - 1923.e25

Published: May 1, 2022

Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth expansion to neighboring distal tissues. The study phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout mouse model Kras;Trp53(KP)-driven lung adenocarcinoma tracked tumor from single-transformed metastatic tumors at unprecedented resolution. We found loss initial, stable alveolar-type2-like state was accompanied transient increase in plasticity. This followed adoption distinct transcriptional programs rapid and, ultimately, clonal sweep subclones capable metastasizing. Finally, develop through stereotypical evolutionary trajectories, perturbing additional suppressors accelerates progression creating novel trajectories. Our elucidates hierarchical nature more broadly, enables in-depth studies progression.

Language: Английский

Citations

221
Non-Small-Cell Lung Cancer in 2022: A Review for General Practitioners in Oncology DOI Creative Commons

Hamid Mithoowani,

Michela Febbraro

Current Oncology, Journal Year: 2022, Volume and Issue: 29(3), P. 1828 - 1839

Published: March 9, 2022

Lung cancer is the leading cause of death in Canada and a significant morbidity for patients their loved ones. There have been rapid advances preventing, screening treating this disease. Here, we present contemporary review treatment non-small cell lung based on current best practices. The focus to highlight recent data cancer, management with early locally-advanced as well metastatic special incorporation immunotherapy into practice its associated toxicities.

Language: Английский

Citations

178
Tumor biomarkers for diagnosis, prognosis and targeted therapy DOI Creative Commons
Yue Zhou, Lei Tao, Jiahao Qiu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

Citations

148
Glutaminase inhibition impairs CD8 T cell activation in STK11-/Lkb1-deficient lung cancer DOI Creative Commons
Sarah A. Best,

Patrick M. Gubser,

Shalini Sethumadhavan

et al.

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(6), P. 874 - 887.e6

Published: May 2, 2022

The tumor microenvironment (TME) contains a rich source of nutrients that sustains cell growth and facilitate development. Glucose glutamine in the TME are essential for development activation effector T cells exert antitumor function. Immunotherapy unleashes function, although many solid tumors respond well, significant proportion patients do not benefit. In with KRAS-mutant lung adenocarcinoma, KEAP1 STK11/Lkb1 co-mutations associated impaired response to immunotherapy. To investigate metabolic immune we generated murine models reflect mutational landscape these patients. Here, show increased glutamate abundance Lkb1-deficient CD8 anti-PD1. Combination treatment glutaminase inhibitor CB-839 inhibited clonal expansion cells. Thus, inhibition negatively impacts activated by anti-PD1

Language: Английский

Citations

105
Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment DOI
Giulia Petroni,

Aitziber Buqué,

Lisa M. Coussens

et al.

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(6), P. 440 - 462

Published: March 15, 2022

Language: Английский

Citations

99
Uridine-derived ribose fuels glucose-restricted pancreatic cancer DOI Creative Commons
Zeribe C. Nwosu, Matthew H. Ward, Peter Sajjakulnukit

et al.

Nature, Journal Year: 2023, Volume and Issue: 618(7963), P. 151 - 158

Published: May 17, 2023

Abstract Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy 1,2 . This mediated in part by complex tumour microenvironment 3 , low vascularity 4 and metabolic aberrations 5,6 Although altered metabolism drives progression, the spectrum of metabolites used as nutrients PDA remains largely unknown. Here we identified uridine fuel for glucose-deprived conditions assessing how more than 175 impacted activity 21 pancreatic cell lines under nutrient restriction. Uridine utilization strongly correlated with expression phosphorylase 1 (UPP1), which demonstrate liberates uridine-derived ribose central carbon thereby support redox balance, survival proliferation glucose-restricted cells. In PDA, UPP1 regulated KRAS–MAPK signalling augmented Consistently, tumours expressed high compared non-tumoural tissues, poor cohorts patients PDA. available microenvironment, demonstrated that actively catabolized tumours. Finally, deletion restricted ability cells use blunted growth immunocompetent mouse models. Our data identify an important compensatory process nutrient-deprived cells, suggesting novel axis therapy.

Language: Английский

Citations

83
NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer DOI Creative Commons
Tommy Weiss‐Sadan, Maolin Ge, Makiko Hayashi

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(3), P. 487 - 503.e7

Published: Feb. 24, 2023

Language: Английский

Citations

76
Cancer cell metabolism and antitumour immunity DOI
Mara De Martino, Jeffrey C. Rathmell, Lorenzo Galluzzi

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(9), P. 654 - 669

Published: April 22, 2024

Language: Английский

Citations

54
Next batter up! Targeting cancers with KRAS-G12D mutations DOI Creative Commons
Mara N. Zeissig, Lauren M. Ashwood, Olga Kondrashova

et al.

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(11), P. 955 - 967

Published: Aug. 15, 2023

KRAS is the most frequently mutated oncogene in cancer. Activating mutations codon 12, especially G12D, have highest prevalence across a range of carcinomas and adenocarcinomas. With inhibitors to KRAS-G12D now entering clinical trials, understanding biology cancers, identifying biomarkers that predict therapeutic response crucial. In this Review, we discuss genomics adenocarcinomas, including histological features, transcriptional landscape, immune microenvironment, how these factors influence therapy. Moreover, explore potential strategies using novel G12D inhibitors, leveraging knowledge gained from trials G12C inhibitors.

Language: Английский

Citations

43