Modulating Glycolysis to Improve Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2606 - 2606

Published: Jan. 30, 2023

Cancer cells undergo metabolic reprogramming and switch to a ‘glycolysis-dominant’ profile promote their survival meet requirements for energy macromolecules. This phenomenon, also known as the ‘Warburg effect,’ provides advantage cancer make tumor environment more pro-cancerous. Additionally, increased glycolytic dependence promotes chemo/radio resistance. A similar is shown by immune in microenvironment, inducing competition between tumor-infiltrating over nutrients. Several recent studies have that targeting enhanced glycolysis promising strategy them susceptible treatment with other conventional modalities, including chemotherapy, radiotherapy, hormonal therapy, immunotherapy, photodynamic therapy. Although several strategies been developed of are different stages pre-clinical clinical evaluation, there still lack effective specifically target cell improve efficacy. Herein, we reviewed our current understanding role how this phenomenon could be potential efficacy

Language: Английский

---

Unveiling the mechanisms and challenges of cancer drug resistance

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Language: Английский

---

Altered metabolism in cancer: insights into energy pathways and therapeutic targets

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 18, 2024

Language: Английский

---

Targeting glycolysis: exploring a new frontier in glioblastoma therapy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Glioblastoma(GBM) is a highly malignant primary central nervous system tumor that poses significant threat to patient survival due its treatment resistance and rapid recurrence.Current options, including maximal safe surgical resection, radiotherapy, temozolomide (TMZ) chemotherapy, have limited efficacy.In recent years, the role of glycolytic metabolic reprogramming in GBM has garnered increasing attention. This review delves into pivotal GBM, with particular focus on multifaceted roles lactate, key product, within microenvironment (TME). Lactate been implicated promoting cell proliferation, invasion, immune evasion. Additionally, this systematically analyzes potential therapeutic strategies targeting molecules pathway, such as Glucose Transporters (GLUTs), Monocarboxylate Transporters(MCTs), Hexokinase 2 (HK2), 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), Pyruvate Kinase Isozyme Type M2 (PKM2), Dehydrogenase A (LDHA). These studies provide novel perspective for treatment. Despite progress made existing research, challenges remain, drug penetration across blood-brain barrier, side effects, resistance. Future research will aim address these by improving delivery, minimizing exploring combination therapies immunotherapy develop more precise effective personalized GBM.

Language: Английский

---

Amplifying cancer treatment: advances in tumor immunotherapy and nanoparticle-based hyperthermia

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 6, 2023

In the quest for cancer treatment modalities with greater effectiveness, combination of tumor immunotherapy and nanoparticle-based hyperthermia has emerged as a promising frontier. The present article provides comprehensive review recent advances cutting-edge research in this burgeoning field examines how these two strategies can be effectively integrated. Tumor immunotherapy, which harnesses immune system to recognize attack cells, shown considerable promise. Concurrently, hyperthermia, utilizes nanotechnology promote selective cell death by raising temperature an innovative therapeutic approach. While both have individually potential, may amplify anti-tumor responses, improved outcomes reduced side effects. Key studies illustrating synergistic effects approaches are highlighted, current challenges future prospects discussed. As we stand on precipice new era treatment, underscores importance continued collaboration bringing treatments from bench bedside.

Language: Английский

---

Current Advances on Nanomaterials Interfering with Lactate Metabolism for Tumor Therapy

Advanced Science, Journal Year: 2023, Volume and Issue: 11(3)

Published: Nov. 8, 2023

Abstract Increasing numbers of studies have shown that tumor cells prefer fermentative glycolysis over oxidative phosphorylation to provide a vast amount energy for fast proliferation even under oxygen‐sufficient conditions. This metabolic alteration not only favors cell progression and metastasis but also increases lactate accumulation in solid tumors. In addition serving as byproduct glycolytic cells, plays central role the construction acidic immunosuppressive microenvironment, resulting therapeutic tolerance. Recently, targeted drug delivery inherent properties nanomaterials attracted great attention, research on modulating metabolism based enhance antitumor therapy has exploded. this review, advanced strategies interfere with are discussed, including inhibiting anabolism, promoting catabolism, disrupting “lactate shuttle”. Furthermore, recent advances combining modulation other therapies, chemotherapy, immunotherapy, photothermal therapy, reactive oxygen species‐related etc., which achieved cooperatively enhanced outcomes, summarized. Finally, foreseeable challenges prospective developments reviewed future development field.

Language: Английский

---

Mitochondria-Targeted Multifunctional Nanoprodrugs by Inhibiting Metabolic Reprogramming for Combating Cisplatin-Resistant Lung Cancer

ACS Nano, Journal Year: 2024, Volume and Issue: 18(32), P. 21156 - 21170

Published: Aug. 1, 2024

How to address the resistance of cisplatin (CDDP) has always been a clinical challenge. The mechanism platinum-based drugs is very complex, including nuclear DNA damage repair, apoptosis escape, and tumor metabolism reprogramming. Tumor cells can switch between mitochondrial oxidative phosphorylation (OXPHOS) glycolysis develop chemotherapy through metabolic variability. In addition, due lack histone protection relatively weak repair ability, (mtDNA) more susceptible damage, which in turn affects OXPHOS become potential target for drugs. Therefore, mitochondria, as targets anticancer drugs, have hot topic research. This study constructed self-assembled nanotargeted drug delivery system LND-SS-Pt-TPP/HA-CD. β-Cyclodextrin-grafted hydronic acid (HA-CD)-encapsulated prodrug nanoparticles CD44 on surface further deliver intracellular mitochondria triphenylphosphine group (TPP+). Disulfide bonds be selectively degraded by glutathione (GSH) releasing lonidamine (LND) (Pt(IV)). Under action GSH ascorbic acid, Pt(IV) reduced (Pt(II)). Cisplatin cause mtDNA induce dysfunction mitophagy, then affect OXPHOS. Meanwhile, LND reduce hexokinase II (HK II) level, destruction block energy supply inhibition. Ultimately, this nano targeted synergistically kill cisplatin-resistant lung cancer cells, supplies an overcome choice via disrupt therapy.

Language: Английский

---

Metabolic crossroads: unravelling immune cell dynamics in gastrointestinal cancer drug resistance

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance gastrointestinal cancers (GI), particularly through pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth reshape TME, creating conditions such as nutrient depletion, hypoxia, acidity that impair antitumor immune responses. Immune TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes promote progression reduce efficacy therapies. The competition for essential nutrients, glucose, between cancer compromises functions effector cells, T cells. Additionally, by-products like lactate kynurenine further suppress activity populations, including regulatory M2 macrophages. Targeting glycolysis presents new opportunities overcome improve therapeutic outcomes GI cancers. Modulating these key has potential reinvigorate exhausted shift toward phenotypes, enhance effectiveness immunotherapies other treatments. Future strategies will require continued research into metabolism, development novel inhibitors, clinical trials evaluating combination Identifying validating biomarkers be crucial patient stratification treatment monitoring. Insights may have broader implications across multiple types, offering avenues improving treatment.

Language: Английский

---

Combined inhibition of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase a induces metabolic and signaling reprogramming and enhances lung adenocarcinoma cell killing

Cancer Letters, Journal Year: 2023, Volume and Issue: 577, P. 216425 - 216425

Published: Oct. 5, 2023

Language: Английский

---

Mitochondrial signaling pathways and their role in cancer drug resistance

Cellular Signalling, Journal Year: 2024, Volume and Issue: 122, P. 111329 - 111329

Published: Aug. 5, 2024

Language: Английский

---