Cabozantinib for the treatment of renal cell carcinoma

Escudier, Bernard; Lougheed, Julie C.; Albigès, Laurence

doi:10.1080/14656566.2016.1258059

Cited by 22 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Strikingly, we observed substantial differences in the responses of PDC cultures and commercially available cell lines, particularly toward cabozantinib and everolimus. Caki1 and 769 P cells were almost resistant to cabozantinib, an inhibitor of the VEGF, MET, and AXL receptors [16]. In contrast, PDC cultures displayed distinct sensitivities toward this agent, which may be reflective of recent findings presenting it as the most efficacious newly developed tyrosine kinase inhibitor in vivo [17].…”

Section: Establishing a Living Biobank Of Pdcs From Ccrccsmentioning

confidence: 90%

Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma

Bolck

Corrò

Kahraman

et al. 2021

European Urology Focus

View full text Add to dashboard Cite

Background: Extensive DNA sequencing has led to an unprecedented view of the diversity of individual genomes and their evolution among patients with clear cell renal cell carcinoma (ccRCC). Objective: To understand subclonal architecture and dynamics of patient-derived two-dimensional (2D) and three-dimensional (3D) ccRCC models in vitro, in order to determine whether they mirror ccRCC inter-and intratumor heterogeneity. Design, setting, and participants: We have established a comprehensive platform of living renal cancer cell models from ccRCC surgical specimens. Outcome measurements and statistical analysis: We confirmed the concordance of 2D and 3D patient-derived cell (PDC) models with the original tumor tissue in terms of histology, biomarker expression, cancer driver mutations, and copy number alterations. We addressed inter-and intrapatient heterogeneity by analyzing clonal dynamics during serial passaging. Results and limitations: In-depth genetic characterization verified the presence of heterogeneous cell populations, and revealed a high degree of similarity between subclonal compositions of monolayer and organoid cell cultures and the corresponding parental ccRCCs. Clonal dynamics were evident during serial passaging of cells in vitro, suggesting that PDC cultures can offer insights into evolutionary potential and treatment susceptibility of ccRCC subclones in vivo. Proof-of-concept drug profiling using selected ccRCC-targeted therapy agents highlighted patient-specific vulnerabilities in PDC models that could not be anticipated by interrogating commercially available cell lines. Conclusions: We demonstrate that PDC models mirror inter-and intratumor heterogeneity of ccRCC in vitro. Based on our findings, we envision that the use of these models will advance our understanding of the trajectories that cause genetic diversity and their consequences for treatment on an individual level. Patient summary: In this study, we developed two-and three-dimensional patient-derived models from clear cell renal cell carcinoma (ccRCC) as "mini-tumors in a dish." We show that these cell models retain important features of the human ccRCCs such as the profound tumor heterogeneity, thus highlighting their importance for cancer research and precision medicine.

show abstract

Section: Establishing a Living Biobank Of Pdcs From Ccrccsmentioning

confidence: 90%

Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma

Bolck

Corrò

Kahraman

et al. 2021

European Urology Focus

View full text Add to dashboard Cite

show abstract

“…Cabozantinib (XL184) is a small molecule inhibitor of Met and AXL [ 86 , 87 ], and has been approved by the FDA for the treatment in progressive metastatic thyroid medullary carcinoma [ 60 , 88 ], and also for advanced renal cell carcinoma after the implementation of antiangiogenic therapy regimens [ 89 ]. Wakelee divided NSCLC patients into three groups as follows: the first two groups were administered erlotinib alone (150 mg poqd) and cabozantinib alone (60 mg poqd), whereas the third group was administered combination therapy (150 mg erlotinib/40 mg cabozantinib).…”

Section: Current Clinical Trials Targeting C-metmentioning

confidence: 99%

Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities

et al. 2018

View full text Add to dashboard Cite

c-Met is a receptor tyrosine kinase belonging to the MET (MNNG HOS transforming gene) family, and is expressed on the surfaces of various cells. Hepatocyte growth factor (HGF) is the ligand for this receptor. The binding of HGF to c-Met initiates a series of intracellular signals that mediate embryogenesis and wound healing in normal cells. However, in cancer cells, aberrant HGF/c-Met axis activation, which is closely related to c-Met gene mutations, overexpression, and amplification, promotes tumor development and progression by stimulating the PI3K/AKT, Ras/MAPK, JAK/STAT, SRC, Wnt/β-catenin, and other signaling pathways. Thus, c-Met and its associated signaling pathways are clinically important therapeutic targets. In this review, we elaborate on the molecular structure of c-Met and HGF and the mechanism through which their interaction activates the PI3K/AKT, Ras/MAPK, and Wnt signaling pathways. We also summarize the connection between c-Met and RON and EGFR, which are also receptor tyrosine kinases. Finally, we introduce the current therapeutic drugs that target c-Met in primary tumors, and their use in clinical research.

show abstract

“…В грудні 2017 року Food and Drug Administration (FDA) видала дозвіл на призначення кабозантинібу (Cabometyx ® американської компанії Exelixis, Inc.) як препарату першої лінії в лікуванні хворих на метастатичний рак нирки [3,[13][14][15][16][17][18][19][20][21][22][23][24][25]. Попередньо, 25 квітня 2016 року, даний препарат був дозволений для використання у хворих на метастатичний рак нирки у другій лінії, після прогресії раку при лікуванні антиангіогенними препаратами першої лінії або при прогресії після лікування препаратами першої лінії [19,21,[26][27][28][29].…”

Section: результатиunclassified

Місце Таргетного Препарату Кабозантиніб У Лікуванні Метастатичного Світлоклітинного Раку Нирки

Yakovlev¹

2021

View full text Add to dashboard Cite

Рак нирки в Україні входить до десятки найпоширеніших онкопатологій. Серед чоловічого населення він посідає восьме місце за поширеністю (4,3 % всіх випадків раку в 2017 році) та десяте місце за причиною смерті (3,7 % всіх випадків смерті від раку у 2017 році). В 2016 році зареєстровано 2758 нових випадків захворювання на рак нирки серед чоловіків (16,4 нового випадку на 100 тис. населення) та 1901 новий випадок серед жінок (9,8 нового випадку на 100 тис. населення), що порівняно з попереднім роком свідчило про зменшення захворюваності для чоловічого населення на 1,1 %, проте зростання захворюваності для жінок на 2,8 %. IV стадію раку нирки на момент встановлення діагнозу мали 22,4 % хворих [1]. Хоча в структурі онкологічної захворюваності чоловіків рак нирки поступається за поширеністю раку простати та сечового міхура, а в структурі жіночої онкозахворюваності рак нирки не входить до десятки найпоширеніших онконозологій, вищенаведені статистичні дані та клініко-соціально-економічна значущість патології обумовлює актуальність цієї проблеми в практиці лікаря.Мета роботи: представити сучасні стандарти лікування метастатичного світлоклітинного раку нирки та визначити місце таргетного препарату кабозантиніб (Cabometyx ® , Exelixis, Inc., США) в схемах системної терапії.Проведено ретроспективний аналіз публікацій із ключовим словом «кабозантиніб».© «Практична онкологія» / «Практическая онкология» / «Practical oncology» (« »), 2019

show abstract

Cabozantinib for the treatment of renal cell carcinoma

Cited by 22 publications

References 35 publications

Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma

Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma

Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities

Місце Таргетного Препарату Кабозантиніб У Лікуванні Метастатичного Світлоклітинного Раку Нирки

Contact Info

Product

Resources

About