Cancer metabolism: looking forward

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(10), P. 669 - 680

Published: July 16, 2021

Language: Английский

---

Targeting PI3K/Akt signal transduction for cancer therapy

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

Published: Dec. 16, 2021

Abstract The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated cancers, contributing to the occurrence progression of tumors. Examining upstream downstream nodes this could allow full elucidation its function. Based on accumulating evidence, strategies targeting major components might provide new insights for cancer drug discovery. Researchers have explored use some inhibitors block survival pathways. However, because oncogenic PI3K activation occurs through mechanisms, clinical efficacies these are limited. Moreover, accompanied by development therapeutic resistance. Therefore, involving other treatments combination solve dilemma. In review, we discuss roles PI3K/Akt phenotypes, review current statuses different inhibitors, introduce therapies consisting signaling conventional therapies. information presented herein suggests that cascading pathway, either alone or with therapies, most effective treatment strategy cancer.

Language: Английский

---

Treatment landscape of triple-negative breast cancer — expanded options, evolving needs

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(2), P. 91 - 113

Published: Nov. 9, 2021

Language: Английский

---

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 18, 2023

Abstract The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, growth, and cycle progression. Growth factor signalling to transcription factors the PAM axis regulated by multiple cross-interactions with several other pathways, dysregulation of can predispose cancer development. most frequently activated human often implicated resistance anticancer therapies. Dysfunction components this such as hyperactivity PI3K, loss function PTEN, gain-of-function AKT, are notorious drivers treatment disease progression cancer. In review we highlight major dysregulations cancer, discuss results AKT mTOR inhibitors monotherapy co-administation antineoplastic agents clinical trials strategy for overcoming resistance. Finally, mechanisms targeted therapies, including immunology immunotherapies also discussed.

Language: Английский

---

Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(49), P. 31189 - 31197

Published: Nov. 23, 2020

Significance This work demonstrates that oncogenic activation of the PI3K-AKT-mTOR signaling pathway suppresses ferroptosis via sterol regulatory element-binding protein-mediated lipogenesis, and inhibition this potentiates cancer therapeutic effect induction. finding unveils mechanisms for regulation provides a potential approach treating patients bearing tumorigenic mutations in pathway.

Language: Английский

---

KRAS mutation: from undruggable to druggable in cancer

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

---

Revisiting the Warburg effect: historical dogma versus current understanding

The Journal of Physiology, Journal Year: 2020, Volume and Issue: 599(6), P. 1745 - 1757

Published: Dec. 22, 2020

Abstract Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary, permanent and universal consequence of dysfunctional or impaired mitochondria compensating for poor ATP yield per mole glucose. Instead, in most tumours the Warburg effect an essential part ‘selfish’ metabolic reprogramming, which results from interplay between (normoxic/hypoxic) hypoxia‐inducible factor‐1 (HIF‐1) overexpression, oncogene activation (cMyc, Ras), loss function tumour suppressors (mutant p53, mutant phosphatase tensin homologue (PTEN), microRNAs sirtuins with suppressor functions), activated (PI3K–Akt–mTORC1, Ras–Raf–MEK–ERK–cMyc, Jak–Stat3) deactivated (LKB1–AMPK) signalling pathways, components microenvironment, HIF‐1 cooperation epigenetic mechanisms. Molecular functional processes include: (a) considerable acceleration glycolytic fluxes; (b) adequate generation unit time maintain energy homeostasis electrochemical gradients; (c) backup diversion intermediates facilitating biosynthesis nucleotides, non‐essential amino acids, lipids hexosamines; (d) inhibition pyruvate entry into mitochondria; (e) excessive formation accumulation lactate, stimulates growth suppression anti‐tumour immunity – addition, lactate can serve as source normoxic cancer cells drives malignant progression resistances conventional therapies; (f) cytosolic being mainly exported through upregulated lactate–proton symporters (MCT4), working together other H + transporters, carbonic anhydrases (CAII, CAIX), hydrate CO 2 oxidative metabolism form bicarbonate; (g) these proton export mechanisms, concert vascular drainage, responsible extracellular acidification, driving resistance (h) maintenance cellular redox low reactive oxygen species (ROS) formation; (i) p53 PTEN, inhibit mitochondrial biogenesis functions, negatively impacting respiration rate. The switch early event oncogenesis primarily supports cell survival. All all, effect, i.e. presence principle functioning mitochondria, constitutes major driver machinery, therapies, patient outcome. However, evidenced during last two decades, minority primary defects play key role promoting due mutations some Krebs cycle enzymes ROS overproduction. image

Language: Английский

---

LncRNA‐mediated posttranslational modifications and reprogramming of energy metabolism in cancer

Cancer Communications, Journal Year: 2020, Volume and Issue: 41(2), P. 109 - 120

Published: Oct. 29, 2020

Abstract Altered metabolism is a hallmark of cancer, and the reprogramming energy has historically been considered general phenomenon tumors. It well recognized that long noncoding RNAs (lncRNAs) regulate in cancer. However, lncRNA‐mediated posttranslational modifications metabolic are unclear at present. In this review, we summarized current understanding interactions between alterations cancer‐associated enzymes, transcription factors, other proteins involved pathways. addition, discuss mechanisms through which these contribute to tumor initiation progression, key roles clinical significance functional lncRNAs. We believe an in‐depth cancer can help identify cellular vulnerabilities be exploited for diagnosis therapy.

Language: Английский

---

Glioma targeted therapy: insight into future of molecular approaches

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 8, 2022

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males susceptible than females. According to fifth edition WHO Classification Tumors Central Nervous System (WHO CNS5), standard care and prognosis can be dramatically different. Generally, circumscribed usually benign recommended early complete resection, with chemotherapy if necessary. Diffuse other high-grade according their molecule subtype slightly intractable, necessity chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide define current care. Here, we discuss novel or potential targets treatment gliomas, especially IDH-wild glioblastoma. Classic such as p53 retinoblastoma (RB) pathway epidermal growth factor receptor (EGFR) gene alteration have met failure due complex regulatory network. There is ever-increasing interest immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), microenvironment, combination several efficacious methods. With many targeted therapy options emerging, biomarkers guiding prescription a particular also attractive. More pre-clinical clinical trials urgently needed explore evaluate feasibility corresponding effective personalized options.

Language: Английский

---

Metabolomics in cancer research and emerging applications in clinical oncology

CA A Cancer Journal for Clinicians, Journal Year: 2021, Volume and Issue: 71(4), P. 333 - 358

Published: May 13, 2021

Abstract Cancer has myriad effects on metabolism that include both rewiring of intracellular to enable cancer cells proliferate inappropriately and adapt the tumor microenvironment, changes in normal tissue metabolism. With recognition fluorodeoxyglucose‐positron emission tomography imaging is an important tool for management many cancers, other metabolites biological samples have been spotlight diagnosis, monitoring, therapy. Metabolomics global analysis small molecule like ‐omics technologies can provide critical information about state are otherwise not apparent. Here, authors review how therapies interact with at cellular systemic levels. An overview metabolomics provided a focus currently available they applied clinical translational research setting. The also discuss could be further leveraged future improve patients cancer.

Language: Английский

---