A Review: Novel Therapies for Advanced Clear Cell Renal Cell Carcinoma DOI Creative Commons
Nataliya Mar, Sami Dwabe, Dalia Kaakour

et al.

Kidney Cancer, Journal Year: 2024, Volume and Issue: 8(1), P. 149 - 157

Published: Jan. 1, 2024

The therapeutic landscape of clear cell renal carcinoma (ccRCC) has dramatically evolved in the last decade. Immuno-oncology (IO) and/or tyrosine kinase inhibitor (TKI) based doublet therapies have become standard frontline setting for most patients with advanced ccRCC. For previously-treated ccRCC, multiple agents are available including belzutifan, a hypoxia inducible factor 2 alpha (HIF2-α) inhibitor. However, challenging goal developing unique mechanism action remains. Many such promising currently development as novel TKIs, inhibitors targeting alternative checkpoints, cellular therapies, radioligands, antibody-drug conjugates, and fatty acid metabolism. Further, role microbiome is being actively investigated ongoing studies evaluating its effect when combined therapies. Mature data from trials these eagerly awaited.

Language: Английский

Evaluation of Advanced Nanomaterials for Cancer Diagnosis and Treatment DOI Creative Commons
N Ndlovu, W. B. Mdlalose, Bulelwa Ntsendwana

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(4), P. 473 - 473

Published: March 28, 2024

Cancer is a persistent global disease and threat to the human species, with numerous cases reported every year. Over recent decades, steady but slowly increasing mortality rate has been observed. While many attempts have made using conventional methods alone as theragnostic strategy, they yielded very little success. Most of shortcomings such can be attributed high demands industrial growth ever-increasing environmental pollution. This requires some high-tech biomedical interventions other solutions. Thus, researchers compelled explore alternative methods. brought much attention nanotechnology applications, specifically magnetic nanomaterials, sole or conjugated The exponential nanomaterials overlapping applications in various fields due their potential properties, which depend on type synthesis route used. Either top-down bottom-up strategies synthesize types NPs. only branches out one method, i.e., physical, two methods, chemical biological syntheses. review highlights techniques, nanoparticle properties each technique produces, use field, more for cancer. Despite evident drawbacks, success achieved furthering complex cancer stages locations unmatched.

Language: Английский

Citations

7
Therapeutic options for different metastatic sites arising from renal cell carcinoma: A review DOI Creative Commons
Xue Wang,

Qian Lin,

Zengxing Qian

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(21), P. e38268 - e38268

Published: May 24, 2024

Renal cell carcinoma (RCC) stands among the top 10 malignant neoplasms with highest fatality rates. It exhibits pronounced heterogeneity and robust metastatic behavior. Patients RCC may present solitary or multiple lesions at various anatomical sites, their prognoses are contingent upon site of metastasis. When deliberating optimal therapeutic approach for a patient, thorough evaluation significant risk factors such as feasibility complete resection, presence oligometastases, patient’s functional physical condition is imperative. Recognizing nuanced differences in metastasis to distinct organs proves advantageous contemplating potential treatment modalities aimed optimizing survival outcomes. Moreover, discerning holds promise enhancing stratification individuals RCC. This review summarizes recent data pertaining current status different sites elucidates role informing clinical management strategies across diverse locales

Language: Английский

Citations

2
Molecular Dynamics Reveals Altered Interactions between Belzutifan and HIF-2 with Natural Variant G323E or Proximal Phosphorylation at T324 DOI Creative Commons

Vishva Natarajan,

Vardhan Satalkar, James C. Gumbart

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(36), P. 37843 - 37855

Published: Aug. 26, 2024

In patients with von-Hippel Lindau (VHL) disease, hypoxia-independent accumulation of HIF-2α leads to increased transcriptional activity HIF-2α:ARNT that drives cancers such as renal cell carcinoma. Belzutifan, a recently FDA-approved drug, is designed prevent the HIF-2α:ARNT, thereby overcoming consequences its unnatural in VHL-dependent cancers. Emerging evidence suggests naturally occurring variant G323E located drug binding pocket prevents inhibitory belzutifan analogs, though mechanism inhibition remains unclear. Interestingly, proximal phosphorylation at neighboring T324, previously shown regulate HIF-2 protein interactions, has also been proposed affect binding. Here, we used molecular dynamics (MD) simulations understand and compare molecular-level effects phospho-T324 (pT324) on bound-HIF-2α:ARNT complex. We find both pT324 increase structural flexibility within site reduce apparent affinity for belzutifan. Whereas are concentrated Fα helix PAS-B domain, decreased stabilized heterodimer through an alternate involving polar interactions between PAS-A domains. Further analysis via ensemble machine learning uncovered important distinct interchain residue modified by pT324. These findings reveal G323E-induced resistance suggest may efficacy allosteric effects.

Language: Английский

Citations

1
Clear Cell Renal Cell Carcinoma: Characterizing the Phenotype of Von Hippel–Lindau Mutation Using MRI DOI
Xu Bai, Cheng Peng, Baichuan Liu

et al.

Journal of Magnetic Resonance Imaging, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Background The von Hippel–Lindau (VHL) mutation is an important alteration in clear cell renal carcinoma (ccRCC); however, its imaging phenotype remains unclear. Purpose To investigate whether MRI features can reflect the VHL status. Study Type Retrospective. Field Strength/Sequence 3 T/fast spin echo T2‐weighted, spin‐echo planar diffusion‐weighted, gradient recalled T1‐weighted, chemical‐shift and contrast‐enhanced T1‐weighted sequences. Population One hundred five patients with ccRCC who underwent preoperative subsequent genomic sequencing: 59 consecutive from our institution (38 [64.41%] mutations) formed a training cohort, 46 Cancer Genome Atlas (TCGA) database (24 [52.17%] independent test cohort. Assessment Two radiologists, 23 33 years of experience respectively, jointly evaluated semantic primary lesion ccRCCs to propose potential related mutations both cohorts. Three additional readers, 5, 7, 10 independently reviewed all lesions assess interobserver agreement features. A mutational likelihood score (VHL‐MULIS) system was constructed using cohort validated Statistical Tests Fisher's or chi‐square test, t ‐test Mann–Whitney U logistic regression, Cohen's kappa ( κ ), area under receiver operating characteristic curve (AUC). two‐sided P value <0.05 considered statistically significant. Results In local public cohorts, T2‐weighted signal intensity presence microscopic fat were significantly associated VHL‐MULIS incorporated maximum diameter, intensity, demonstrated promising diagnostic ability (AUC, 0.82; sensitivity, 0.79; specificity, 0.82) substantial , 0.787) Data Conclusion exhibited distinct phenotype. Integrating multiple has status ccRCC. Evidence Level Technical Efficacy Stage 2

Language: Английский

Citations

1
Advancements in understanding the molecular mechanisms and clinical implications of Von Hippel-Lindau syndrome: A comprehensive review DOI Creative Commons
Y Wang, Jian Song,

Shuxing Zheng

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 51, P. 102193 - 102193

Published: Nov. 21, 2024

Language: Английский

Citations

1
Hypoxia, Stem Cells and Cancer Stem Cells DOI
Mostafa Manian,

Marjan Taherian,

Hamid Nickho

et al.

Stem cell biology and regenerative medicine, Journal Year: 2024, Volume and Issue: unknown, P. 29 - 114

Published: Jan. 1, 2024

Language: Английский

Citations

1
Correctly identifying the cells of origin is essential for tailoring treatment and understanding the emergence of cancer stem cells and late metastases DOI Creative Commons
Helge L. Waldum, Geir Slupphaug

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: April 10, 2024

Malignancy manifests itself by deregulated growth and the ability to invade surrounding tissues or metastasize other organs. These properties are due genetic and/or epigenetic changes, most often mutations. Many aspects of carcinogenesis known, but cell origin has been insufficiently focused on, which is unfortunate since regulation its essential understand carcinogenic process guide treatment. Similarly, concept cancer stem cells as having stop proliferation rest in a state dormancy being resistant cytotoxic drugs before “waking up” become highly malignant tumor recurrence, not fully understood. Some tumors may recur after decades, phenomenon probably also connected cells. The present review shows that many these questions related differentiated long-term stimulated proliferation.

Language: Английский

Citations

0
PCDHGC3 silencing promotes renal carcinoma metastasis via mTOR/HIF2a and lipid metabolism rewiring DOI Creative Commons
Lucía Celada,

Tamara Cubiella,

Laura Salerno

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 27, 2024

Abstract Clustered protocadherins (cPCDH) are widely expressed in the nervous system with known functions, but their roles cancer, particularly metastasis, largely unexplored. Our previous research revealed that epigenetic silencing of PCDHGC3 is linked to decreased survival neuroendocrine cancer patients. This study investigates ’s role clear cell renal carcinoma (ccRCC). We found expression associated lower and advanced disease stage ccRCC shRNA-mediated lines significantly increased proliferation, invasion, survival. In orthotopic mouse models, promoted metastasis. The mTOR HIF2α pathways were identified as downstream targets activated by loss. Inhibition these counteracted effects silencing, highlighting importance tumor progression. Proteomic metabolomic analyses showed led overexpression proteins involved fatty acid cholesterol synthesis, increasing lipid droplets shifting metabolism. metabolic reprogramming characterizes aggressive ccRCC. emphasizes impact on metastasis suggests or inhibitors potential therapies for -deficient

Language: Английский

Citations

0
Belzutifan Efficacy and Tolerability in Patients with Sporadic Metastatic Clear Cell Renal Cell Carcinoma DOI

Emily Wang,

Eric S Rupe,

Sagar S Mukhida

et al.

European Urology Focus, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

0
A Review: Novel Therapies for Advanced Clear Cell Renal Cell Carcinoma DOI Creative Commons
Nataliya Mar, Sami Dwabe, Dalia Kaakour

et al.

Kidney Cancer, Journal Year: 2024, Volume and Issue: 8(1), P. 149 - 157

Published: Jan. 1, 2024

The therapeutic landscape of clear cell renal carcinoma (ccRCC) has dramatically evolved in the last decade. Immuno-oncology (IO) and/or tyrosine kinase inhibitor (TKI) based doublet therapies have become standard frontline setting for most patients with advanced ccRCC. For previously-treated ccRCC, multiple agents are available including belzutifan, a hypoxia inducible factor 2 alpha (HIF2-α) inhibitor. However, challenging goal developing unique mechanism action remains. Many such promising currently development as novel TKIs, inhibitors targeting alternative checkpoints, cellular therapies, radioligands, antibody-drug conjugates, and fatty acid metabolism. Further, role microbiome is being actively investigated ongoing studies evaluating its effect when combined therapies. Mature data from trials these eagerly awaited.

Language: Английский

Citations

0