Cellular Signalling, Journal Year: 2024, Volume and Issue: 124, P. 111421 - 111421
Published: Sept. 17, 2024
Language: Английский
Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14
Published: Jan. 30, 2024
Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One the main transcription factors activated by hypoxia hypoxia-inducible factor (HIF), which regulates expression genes involved in various aspects tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, cell migration. This can negatively impact patient outcomes inducing therapeutic resistance. The importance clearly demonstrated continued research into finding clinically relevant biomarkers, hypoxia-targeting therapies. problems lack applicable methods detection, standardisation. Additionally, lot detecting do not take consideration complexity hypoxic tumour microenvironment (TME). Therefore, this needs further elucidation as approximately 50% are hypoxic. ECM important component TME, developed both cancer associated fibroblasts (CAFs) cells. However, it distinguish different roles develop biomarkers novel compounds. Fibronectin (FN), collagen (COL) hyaluronic acid (HA) components that create fibres. These fibres crosslinked specific enzymes lysyl oxidase (LOX) stiffness induces fibrosis. partially regulated HIFs. review highlights understanding role current data shows contradictory results on also indicates needed identifying CAF subtypes exact roles; with some showing pro-tumorigenic capacity others having anti-tumorigenic roles. has made difficult fully elucidate CAFs within TME. clear an area requires unravelling strategies target have resulted worsened prognosis. cells discussed been modulating environment. Which led development immunotherapies PD-L1. hypoxia-induced changes confer resistance conventional therapies, such chemotherapy, radiotherapy, immunotherapy. summarizes knowledge TME its implications for therapy It discusses potential prognostic predictive indictors treatment response, well challenges opportunities targeting clinical trials.
Language: Английский
Citations
27
Molecular Aspects of Medicine, Journal Year: 2025, Volume and Issue: 101, P. 101335 - 101335
Published: Jan. 1, 2025
Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 SETD2, which play key roles in signaling pathway transduction, chromatin remodeling DNA repair. The PI3K/AKT/mTOR particularly important the pathogenesis RCC. Mutations such as PIK3CA, MTOR PTEN are associated metabolic abnormalities proliferation. Clinically, mTOR inhibitors VEGF-targeted drugs have shown significant efficacy personalized therapy. Abnormal regulation reprogramming, especially glycolysis glutamine pathways, provides cells continuous energy supply survival advantages, GLS1 promising results preclinical studies. This paper also explores potential immune checkpoint combination targeted drugs, well application nanotechnology drug delivery In addition, unique mechanisms revealed individualized therapeutic strategies explored for specific subtypes TFE3, TFEB rearrangement type SDHB mutant type. review summarizes common gene mutations their mechanisms, emphasizes diagnosis, treatment prognosis, looks forward prospects multi-pathway therapy, immunotherapy treatment, providing theoretical support clinical guidance new development.
Language: Английский
Citations
2
Cancer Cell, Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
Language: Английский
Citations
2
Cancers, Journal Year: 2023, Volume and Issue: 15(12), P. 3207 - 3207
Published: June 16, 2023
Renal cell carcinoma (RCC) belongs to a heterogenous cancer group arising from renal tubular epithelial cells. Among RCC subtypes, clear (ccRCC) is the most common variant, characterized by high aggressiveness, invasiveness and metastatic potential, features that lead poor prognosis mortality rate. In addition, diagnosis of kidney incidental in majority cases, this results late diagnosis, when stage disease advanced tumor has already metastasized. Furthermore, ccRCC treatment complicated its strong resistance chemo- radiotherapy. Therefore, there active ongoing research focused on identifying novel biomarkers which could be useful for assessing better prognosis, as well new molecules used targeted therapy. light, several therapies have been shown effective prolonging overall survival patients. Thus, aim review analyze actual state-of-the-art therapeutic options, while also reporting recent advances biomarker discoveries, exploited or
Language: Английский
Citations
35
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12387 - 12387
Published: Nov. 18, 2024
Cancer is a multifaceted disease influenced by various mechanisms, including the generation of reactive oxygen species (ROS), which have paradoxical role in both promoting cancer progression and serving as targets for therapeutic interventions. At low concentrations, ROS serve signaling agents that enhance cell proliferation, migration, resistance to drugs. However, at elevated levels, induce oxidative stress, causing damage biomolecules leading death. cells developed mechanisms manage activating pathways such NRF2, NF-κB, PI3K/Akt. This review explores relationship between cancer, focusing on death like apoptosis, ferroptosis, autophagy, highlighting potential strategies exploit target cells.
Language: Английский
Citations
12
European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116158 - 116158
Published: Jan. 17, 2024
Renal cell carcinoma (RCC) is the most common renal malignancy with a rapidly increasing morbidity and mortality rate gradually. RCC has high an extremely poor prognosis. Despite numerous treatment strategies, resistant to conventional radiotherapy chemotherapy. In addition, limited clinical efficacy inevitable resistance of multiple agents suggest unmet need. Therefore, there urgent need develop novel anti-RCC candidates. Nowadays many promising results have been achieved development small molecule inhibitors against RCC. This paper reviews recent research progress targeting It focusing on structural optimization process conformational relationships inhibitors, as well potential mechanisms anticancer activities for To provide theoretical basis promoting translation we discussed their application prospects future directions. could be capable improving therapy
Language: Английский
Citations
11
Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown
Published: April 23, 2024
Language: Английский
Citations
11
Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 601 - 601
Published: Jan. 31, 2024
Germline inactivation of the Von Hippel-Lindau (VHL) tumor suppressor is defining hallmark in hereditary VHL disease and VHL-associated renal cell carcinoma (RCC). However, somatic mutations are also observed patients with sporadic RCC. Loss function result constitutive activation hypoxia-inducible factor-2 alpha (HIF-2α), which leads to increased expression HIF target genes that promote angiogenesis growth. As 2023, belzutifan currently only approved HIF-2α inhibitor for both metastatic RCC (mRCC). there potential resistance inhibitors warrants novel HIF-2α-targeting strategies. In this review, we discuss mechanisms current clinical trials evaluating combinations other targeted therapies immune checkpoint may enhance efficacy targeting. Lastly, newer generation under early investigation outline future directions challenges mRCC.
Language: Английский
Citations
10
Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2212 - 2212
Published: April 9, 2023
Cancer-associated inflammation has been established as a hallmark feature of almost all solid cancers. Tumor-extrinsic and intrinsic signaling pathways regulate the process cancer-associated inflammation. is triggered by many factors, including infection, obesity, autoimmune disorders, exposure to toxic radioactive substances. Intrinsic can be induced genomic mutation, genome instability epigenetic remodeling in cancer cells that promote immunosuppressive traits, inducing recruitment activation inflammatory immune cells. In RCC, cell-intrinsic alterations are assembled, upregulating pathways, which enhance chemokine release neoantigen expression. Furthermore, activate endothelium induce metabolic shifts, thereby amplifying both paracrine autocrine loops RCC tumor growth progression. Together with tumor-extrinsic tumor-intrinsic trigger Janus-faced microenvironment, simultaneously promoting or inhibiting growth. For therapeutic success, it important understand pathomechanisms inflammation, this review, we describe molecular mechanisms influence cell functions, increasing malignancy anti-cancer resistance. We also discuss potential anti-inflammatory treatments, may provide clinical benefits RCCs possible avenues for therapy future research.
Language: Английский
Citations
19
Molecular Biology Reports, Journal Year: 2023, Volume and Issue: 51(1)
Published: Dec. 12, 2023
Abstract Typically associated with solid tumors, hypoxia contributes to tumor angiogenesis and lymphangiogenesis through various molecular mechanisms. Accumulating studies indicate that hypoxia-inducible factor is the key transcription coordinating endothelial cells respond in urological cancers, mainly renal cell carcinoma, prostate cancer, bladder cancer. Moreover, it has been suggested microenvironment simultaneously recruits stromal suppress immune activities. This review summarizes mechanisms by which HIF regulates tumorigenesis elaborates on associations between angiogenesis, lymphangiogenesis, cancers.
Language: Английский
Citations
17