Article
Biotechnology & Applied Microbiology
Aaron R. Lim, Benjamin G. Vincent, Alissa M. Weaver, W. Kimryn Rathmell
Summary: This study found that tyrosine kinase inhibitors Sunitinib and Axitinib can increase the secretion of extracellular vesicles (EVs) from human renal cell carcinoma cells. These EVs contained enriched metabolic proteins, particularly GLUT1, which led to higher glucose uptake and glycolytic metabolism. Overall, the findings suggest that these tyrosine kinase inhibitors alter metabolic cargo and activity in RCC EVs.
CANCER GENE THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoyi Du, Zhipeng Zhao, Xin Zhao, Hexi Wang, Li Jiang, Wei Tang
Summary: In this study, we analyzed the subtypes of ccRCC mediated by 8 TSGs contained in the 3p21.3 gene cluster and their effects on TME cell infiltration. A risk score model was established to predict prognosis and drug sensitivity. The hub gene NPRL2 was found to promote sunitinib sensitivity in ccRCC cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
T. K. Choueiri, T. Powles, M. Burotto, B. Escudier, M. T. Bourlon, B. Zurawski, V. M. Oyervides Juarez, J. J. Hsieh, U. Basso, A. Y. Shah, C. Suarez, A. Hamzaj, J. C. Goh, C. Barrios, M. Richardet, C. Porta, R. Kowalyszyn, J. P. Feregrino, J. Zolnierek, D. Pook, E. R. Kessler, Y. Tomita, R. Mizuno, J. Bedke, J. Zhang, M. A. Maurer, B. Simsek, F. Ejzykowicz, G. M. Schwab, A. B. Apolo, R. J. Motzer
Summary: The study demonstrates that nivolumab plus cabozantinib has significant advantages over sunitinib in the treatment of previously untreated advanced renal-cell carcinoma, including progression-free survival, overall survival, and likelihood of response.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Oncology
Yun Peng, Shiqiang Dong, Yuxuan Song, Dingkun Hou, Lili Wang, Bowen Li, Haitao Wang
Summary: This study identified key immune-related genes and hub genes associated with sunitinib and immune infiltration in clear cell RCC (ccRCC), providing insights into sunitinib resistance and potential biomarkers or drug targets for ccRCC.
Article
Cell Biology
Zhipeng Xu, Min Liu, Jin Wang, Kai Liu, Liuyu Xu, Demin Fan, Hui Zhang, Wenxin Hu, Dan Wei, Jianning Wang
Summary: The MYH9 gene is commonly upregulated in clear cell renal cell carcinoma (ccRCC) and its overexpression predicts poor prognosis. Knockdown of MYH9 inhibits the proliferative and metastatic potentials of ccRCC cells, while overexpression enhances these properties. Furthermore, MYH9 plays vital roles through the AKT signaling pathway and determines the response of ccRCC cells to sunitinib treatment.
CELL DEATH DISCOVERY
(2022)
Article
Cell Biology
Yi Shou, Changjie Yue, Qi Wang, Jingchong Liu, Jiaju Xu, Qi Miao, Di Liu, Hongmei Yang, Yuenan Liu, Xiaoping Zhang
Summary: Renal cell carcinoma (RCC) is difficult to diagnose early and prone to metastasis. Sunitinib is the recommended first-line drug for advanced RCC, but adaptive resistance is a major challenge. In this study, circPTPN12 was found to be highly expressed in RCC tissues and associated with poorer clinical outcomes. CircPTPN12 promoted RCC cell proliferation, migration, invasion, and resistance to sunitinib. Mechanistically, circPTPN12 formed a complex with hnRNPM and enhanced its ability to stabilize IL-6 mRNA, activating the STAT3 signaling pathway. This study identifies circPTPN12/hnRNPM/IL-6/STAT3 axis as a promising therapeutic target for relieving sunitinib resistance in RCC.
CELL DEATH & DISEASE
(2023)
Review
Pharmacology & Pharmacy
Juan Jin, Yuhao Xie, Jin-Shi Zhang, Jing-Quan Wang, Shi-Jie Dai, Wen-fang He, Shou-Ye Li, Charles R. Ashby Jr, Zhe-Sheng Chen, Qiang He
Summary: Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer, and targeted therapy with Sunitinib has become the main treatment option due to the lack of efficacy in radiation therapy and chemotherapy. However, many patients develop resistance to Sunitinib within months of therapy. In this review, we discuss the molecular mechanisms of Sunitinib resistance, strategies to overcome it, and potential predictive biomarkers.
DRUG RESISTANCE UPDATES
(2023)
Article
Oncology
Veronica Mollica, Stefano Brocchi, Filippo Gustavo Dall'Olio, Laura Marcolin, Alexandro Paccapelo, Matteo Santoni, Alessandro Rizzo, Rodolfo Montironi, Rita Golfieri, Francesco Massari, Andrea Ardizzoni
Summary: The treatment landscape for metastatic renal cell carcinoma has been significantly altered with the introduction of immunotherapy. Current radiological criteria may not fully capture the benefits from immunotherapy, leading to atypical response patterns like hyperprogression or pseudoprogression. A retrospective study showed a potential deceleration in tumor growth rate and improved survival outcomes when using nivolumab as a second or later line of treatment for patients with metastatic RCC.
Article
Oncology
Meile Mo, Xiaoyun Ma, Yihuan Luo, Chao Tan, Bihu Liu, Peng Tang, Qian Liao, Shun Liu, Hongping Yu, Dongping Huang, Xiaoyun Zeng, Xiaoqiang Qiu
Summary: The study identified a liver-specific lncRNA, FAM99A, which is frequently downregulated in HCC tissues. Decreased FAM99A expression is associated with microvascular invasion and advanced histological grade in HCC patients. The study also found that upregulation of FAM99A inhibits the proliferation, migration, and invasion abilities of HCC cells in vitro and in vivo. The study suggests that FAM99A may serve as a promising prognostic indicator for HCC patients.
Article
Oncology
Zeshen Wu, Yulu Peng, Longbin Xiong, Jun Wang, Zhen Li, Kang Ning, Minhua Deng, Ning Wang, Wensu Wei, Zhiyong Li, Pei Dong, Chunping Yu, Fangjian Zhou, Zhiling Zhang
Summary: This study reveals that Sam68 protein impacts the sensitivity to the drug Sunitinib by mediating cell apoptosis. The expression level of Sam68 is higher in Sunitinib-sensitive tumor tissues, and downregulation of Sam68 inhibits Sunitinib-induced cell apoptosis. These findings suggest that Sam68 expression level may serve as a biomarker for predicting Sunitinib sensitivity in RCC patients.
Article
Oncology
Y. Tomita, R. J. Motzer, T. K. Choueiri, B. I. Rini, H. Miyake, M. Oya, L. Albiges, M. Aizawa, Y. Umeyama, J. Wang, A. di Pietro, M. Schmidinger
Summary: In post hoc analyses, first-line treatment with avelumab + axitinib was generally associated with efficacy benefits versus treatment with sunitinib in patients with advanced renal cell carcinoma across subgroups defined by different numbers of IMDC risk factors or target tumor sites.
Review
Pharmacology & Pharmacy
Yunxia Wang, Xiaolin Liu, Luyao Gong, Weihong Ding, Wenjing Hao, Yeheng Peng, Jun Zhang, Weimin Cai, Yuan Gao
Summary: This review summarizes the mechanisms of sunitinib resistance in renal cell carcinoma, including activation of bypass or alternative pathways, inadequate drug accumulation, tumor microenvironment, metabolic reprogramming, and epigenetic regulation. It also covers current and potential biomarkers as well as treatment strategies for overcoming sunitinib resistance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jun Ito, Shigeki Sugawara, Takeo Tatsuta, Masahiro Hosono, Makoto Sato
Summary: The pretreatment of RCC cells with SAL can enhance the uptake and cytotoxic effects of molecular-targeted drugs, providing a theoretical basis for the development of new drugs for advanced RCC.
Article
Oncology
Robert J. Motzer, Toni K. Choueiri, David F. McDermott, Thomas Powles, Yann-Alexandre Vano, Saurabh Gupta, Jin Yao, Celine Han, Ron Ammar, Simon Papillon-Cavanagh, Shruti S. Saggi, M. Brent McHenry, Petra Ross-Macdonald, Megan Wind-Rotolo
Summary: The study found that biomarkers previously associated with immune checkpoint inhibitor-containing regimens were not predictive for survival in RCC patients treated with nivolumab plus ipilimumab. However, gene expression analysis revealed an association between an inflammatory response and progression-free survival in patients receiving this treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Tomonori Sato, Yoshihide Kawasaki, Masamitsu Maekawa, Shinya Takasaki, Kento Morozumi, Masahiko Sato, Shuichi Shimada, Naoki Kawamorita, Shinichi Yamashita, Koji Mitsuzuka, Nariyasu Mano, Akihiro Ito
Summary: Metabolomics analysis can identify potential therapeutic targets for treatment resistance in cancer, such as sunitinib resistance in renal cell carcinoma (RCC), through changes in metabolites. This study found that alterations in energy metabolism, glycolysis upregulation, and antioxidant activity are associated with sunitinib resistance in RCC cells.
Article
Oncology
R. J. Motzer, A. Alyasova, D. Ye, A. Karpenko, H. Li, B. Alekseev, L. Xie, G. Kurteva, R. Kowalyszyn, O. Karyakin, Y. Neron, T. Cosgriff, L. Collins, T. Brechenmacher, C. Lin, L. Morgan, L. Yang
ANNALS OF ONCOLOGY
(2016)
Article
Oncology
A. Ari Hakimi, Irina Ostrovnaya, Anders Jacobsen, Katalin Susztak, Jonathan A. Coleman, Paul Russo, Andrew G. Winer, Roy Mano, Alexander I. Sankin, Robert J. Motzer, Martin H. Voss, Kenneth Offit, Mark Purdue, Mark Pomerantz, Matthew Freedman, Toni K. Choueiri, James J. Hsieh, Robert J. Klein
Article
Oncology
Ying Chen, Brian I. Rini, Robert J. Motzer, Janice P. Dutcher, Olivier Rixe, George Wilding, Walter M. Stadler, Jamal Tarazi, May Garrett, Yazdi K. Pithavala
Article
Oncology
R. Nadal, A. Amin, D. M. Geynisman, M. H. Voss, M. Weinstock, J. Doyle, Z. Zhang, A. Viudez, E. R. Plimack, D. F. McDermott, R. Motzer, B. Rini, H. J. Hammers
ANNALS OF ONCOLOGY
(2016)
Meeting Abstract
Oncology
Jay Margolis, Nicole Princic, Justin Doan, Gregory Lenhart, Robert J. Motzer
JOURNAL OF CLINICAL ONCOLOGY
(2016)
Meeting Abstract
Oncology
Guillermo de Velasco, Diana Miao, Sachet Shukla, Martin Henner Voss, Catherine Wu, Bradley Murray, Matthew Meyerson, Sabina Signoretti, Robert J. Motzer, Eliezer Mendel Van Allen, Toni K. Choueiri
JOURNAL OF CLINICAL ONCOLOGY
(2016)
Article
Oncology
Thomas Powles, Mark R. Lackner, Stephane Oudard, Bernard Escudier, Christy Ralph, Janet E. Brown, Robert E. Hawkins, Daniel Castellano, Brian I. Rini, Michael D. Staehler, Alain Ravaud, Wei Lin, Bridget O'Keeffe, Yulei Wang, Shan Lu, Jill M. Spoerke, Ling-Yuh Huw, Michelle Byrtek, Rui Zhu, Joseph A. Ware, Robert J. Motzer
JOURNAL OF CLINICAL ONCOLOGY
(2016)
Article
Oncology
Darren R. Feldman, James Hu, Tanya B. Dorff, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Siamak Daneshmand, Charlene Ketchens, Dean F. Bajorin, George J. Bosl, David I. Quinn, Robert J. Motzer
JOURNAL OF CLINICAL ONCOLOGY
(2016)
Letter
Oncology
Robert J. Motzer, Thomas E. Hutson, Min Ren, Corina Dutcus, James Larkin
Article
Oncology
Lauren V. Wood, Antonio Fojo, Brenda D. Roberson, Meghan S. B. Hughes, William Dahut, James L. Gulley, Ravi A. Madan, Philip M. Arlen, Marianna Sabatino, David F. Stroncek, Luciano Castiello, Jane B. Trepel, Min-Jung Lee, Howard L. Parnes, Seth M. Steinberg, Masaki Terabe, Julia Wilkerson, Ira Pastan, Jay A. Berzofsky
Article
Oncology
Julia Wilkerson, Kald Abdallah, Charles Hugh-Jones, Greg Curt, Mace Rothenberg, Ronit Simantov, Martin Murphy, Joseph Morrell, Joel Beetsch, Daniel J. Sargent, Howard I. Scher, Peter Lebowitz, Richard Simon, Wilfred D. Stein, Susan E. Bates, Tito Fojo
Review
Oncology
Mauricio Burotto, Julia Wilkerson, Wilfred D. Stein, Susan E. Bates, Tito Fojo
SEMINARS IN ONCOLOGY
(2019)
Meeting Abstract
Oncology
Harshraj Leuva, Mengxi Zhou, Julia Wilkerson, Keith Sigel, Ta-Chueh Hsu, David Henry Aggen, Erik Langhoff, Yeun-Hee Anna Park, Susan Elaine Bates, Antonio Tito Fojo
JOURNAL OF CLINICAL ONCOLOGY
(2019)
Review
Oncology
Harshraj Leuva, Keith Sigel, Mengxi Zhou, Julia Wilkerson, David H. Aggen, Yeun-Hee Anna Park, Christopher B. Anderson, Ta-Chueh Melody Hsu, Erik Langhoff, Glen McWilliams, Charles G. Drake, Richard Simon, Susan E. Bates, Tito Fojo
SEMINARS IN ONCOLOGY
(2019)
Letter
Medicine, General & Internal
Robert J. Motzer, Bernard Escudier, Toni K. Choueiri
NEW ENGLAND JOURNAL OF MEDICINE
(2016)