The combination of bevacizumab/Avastin and erlotinib/Tarceva is relevant for the treatment of metastatic renal cell carcinoma: the role of a synonymous mutation of the EGFR receptor

Grépin, Renaud; Guyot, Mélanie; Dumond, Aurore; Durivault, Jérôme; Roussel, Jean‐François; Dupré, Florence; Quintens, H.; Pagès, Gilles

doi:10.7150/thno.38346

Cited by 23 publications

(21 citation statements)

References 49 publications

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“…Renal cell carcinoma (RCC) is one of the most frequently diagnosed cancers worldwide, and the incidence rates have been steadily increasing 1 - 3 . More than 10 histological and molecular subtypes of RCC have been identified, among which clear cell RCC (ccRCC) is the most common type and accounting for 80% of all cases 2 , 4 .…”

Section: Introductionmentioning

confidence: 99%

HSPA12A unstabilizes CD147 to inhibit lactate export and migration in human renal cell carcinoma

Min¹,

Zhang²,

Li³

et al. 2020

Theranostics

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Background: Metastasis accounts for 90% of cancer-associated mortality in patients with renal cell carcinoma (RCC). However, the clinical management of RCC metastasis is challenging. Lactate export is known to play an important role in cancer cell migration. This study investigated the role of heat shock protein A12A (HSPA12A) in RCC migration. Methods: HSPA12A expression was examined in 82 pairs of matched RCC tumors and corresponding normal kidney tissues from patients by immunoblotting and immunofluorescence analyses. The proliferation of RCC cells was analyzed using MTT and EdU incorporation assays. The migration of RCC cells was evaluated by wound healing and Transwell migration assays. Extracellular acidification was examined using Seahorse technology. Protein stability was determined following treatment with protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132. Mass spectrometry, immunoprecipitation, and immunoblotting were employed to examine protein-protein interactions. Results: RCC tumors from patients showed downregulation of HSPA12A, which was associated with advanced tumor node metastasis stage. Intriguingly, overexpression of HSPA12A in RCC cells inhibited migration, whereas HSPA12A knockdown had the opposite effect. Lactate export, glycolysis rate, and CD147 protein abundance were also inhibited by HSPA12A overexpression but promoted by HSPA12A knockdown. An interaction of HSPA12A with HRD1 ubiquitin E3 ligase was detected in RCC cells. Further studies demonstrated that CD147 ubiquitination and proteasomal degradation were promoted by HSPA12A overexpression whereas inhibited by HSPA12A knockdown. Notably, the HSPA12A overexpression-induced inhibition of lactate export and migration were abolished by CD147 overexpression. Conclusion: Human RCC shows downregulation of HSPA12A. Overexpression of HSPA12A in RCC cells unstabilizes CD147 through increasing its ubiquitin-proteasome degradation, thereby inhibits lactate export and glycolysis, and ultimately suppresses RCC cell migration. Our results demonstrate that overexpression of HSPA12A might represent a viable strategy for managing RCC metastasis.

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Section: Introductionmentioning

confidence: 99%

HSPA12A unstabilizes CD147 to inhibit lactate export and migration in human renal cell carcinoma

Min¹,

Zhang²,

Li³

et al. 2020

Theranostics

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“…Pieces of evidence such as the drug combination of sunitinib targeted PDGFRA and sorafenib targeted KIT, was proved to be successful for renal cell carcinoma in clinical trial phase 3 . Besides, the combination of erlotinib targeted EGFR and bevacizumab targeted VEGFA, was reported for the treatment of metastatic renal cell carcinoma (Hainsworth et al, 2005). In gynecologic cancers, common genes regulated by prognosisalternative miRNAs such as BCL2, EGFR, PDGFRA, and VEGFA were also demonstrated to be combinational targets for anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Reveal the Regulation Patterns of Prognosis-Related miRNAs and lncRNAs Across Solid Tumors in the Cancer Genome Atlas

Yin

Wang

Yan

et al. 2020

Front. Cell Dev. Biol.

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Background: The dysregulation of non-coding RNAs (ncRNAs) such as miRNAs and lncRNAs are associated with the pathogenesis and progression in multiple cancers including solid tumors. Comprehensive investigations of prognosis-related ncRNA markers could promote the development of therapeutic strategies for solid tumors, but rarely reported. Methods: By taking advantage of The Cancer Genome Atlas (TCGA), pan-cancer prognosis analysis (PCPA) models were firstly constructed based on miRNA and lncRNA expression profiles of 8,450 samples in 19 solid tumors. Further, the co-occurrence and exclusivity among ncRNA markers were systematically analyzed for different cancers. Results: In identified ncRNA makers, 71% of the miRNA markers were shared in multiple cancers, whereas 96% of the lncRNA markers were cancer-specific. Moreover, to analyze the regulation patterns of prognosis-related ncRNAs at the pan-cancer level, miRNA markers were further annotated into eight carcinogenic pathways. Results represented that approximately 86% of these miRNA markers could regulate the PI3K-Akt signaling pathway, while only 48% for the Notch signaling pathway. Finally, among 126 common genes that participated in eight carcinogenic pathways, BCL2, CSNK2A1, EGFR, PDGFRA, and VEGFA were proposed as potential drug targets for multiple cancers. Conclusion: The prognosis analysis and regulation characteristics of ncRNAs presented in this study may help to facilitate the discovery of anti-cancer drugs for multiple solid tumors.

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“…24 At the same time, bevacizumab can normalize the distribution of blood vessels in HCC and its surrounding tissues, which improves the delivery of chemotherapy drugs by reducing the interstitial pressure. 34 The efficacy of bevacizumab in advanced HCC treatment has been initially confirmed. 35 Zhu et al reported a GE2MOX2B scheme for the treatment of advanced liver cancer in a phase II clinical study.…”

Section: Cabozantinibmentioning

confidence: 97%

Section: Small Molecule Targeted Drugsmentioning

confidence: 99%

New Therapeutic Options for Advanced Hepatocellular Carcinoma

Liu

et al. 2020

Cancer Control

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Hepatocellular carcinoma (HCC), one of the most common lethal diseases in the world, has a 5-year survival rate of only 7%. Hepatocellular carcinoma has no symptoms in the early stage but obvious symptoms in the late stage, leading to delayed diagnosis and reduced treatment efficacy. In recent years, as the scope of HCC research has increased in depth, the clinical development and application of molecular targeted drugs and immunotherapy drugs have brought new breakthroughs in HCC treatment. Targeted therapy drugs for HCC have high specificity, allowing them to selectively kill tumor cells and minimize damage to normal tissues. At present, these targeted drugs are mainly classified into 3 categories: small molecule targeted drugs, HCC antigen-specific targeted drugs, and immune checkpoint targeted drugs. This article reviews the latest research progress on the targeted drugs for HCC.

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The combination of bevacizumab/Avastin and erlotinib/Tarceva is relevant for the treatment of metastatic renal cell carcinoma: the role of a synonymous mutation of the EGFR receptor

Cited by 23 publications

References 49 publications

HSPA12A unstabilizes CD147 to inhibit lactate export and migration in human renal cell carcinoma

HSPA12A unstabilizes CD147 to inhibit lactate export and migration in human renal cell carcinoma

Reveal the Regulation Patterns of Prognosis-Related miRNAs and lncRNAs Across Solid Tumors in the Cancer Genome Atlas

New Therapeutic Options for Advanced Hepatocellular Carcinoma

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