Targeting the HIF2–VEGF axis in renal cell carcinoma

Cancer statistics, 2020

(2020) Rebecca L. Siegel et al.   CA-A CANCER JOURNAL FOR CLINICIANS

Phase I/II study of the oral HIF-2 α inhibitor MK-6482 in patients with advanced clear cell renal cell carcinoma (RCC).

(2020) Toni K. Choueiri et al.   JOURNAL OF CLINICAL ONCOLOGY

Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC).

(2020) Nizar M. Tannir et al.   JOURNAL OF CLINICAL ONCOLOGY

Final analysis of the CheckMate 025 trial comparing nivolumab (NIVO) versus everolimus (EVE) with >5 years of follow-up in patients with advanced renal cell carcinoma (aRCC).

(2020) Robert J. Motzer et al.   JOURNAL OF CLINICAL ONCOLOGY

TBK1 Activation by VHL Loss in Renal Cell Carcinoma: A Novel HIF-Independent Vulnerability

(2020) Ziad Bakouny et al.   Cancer Discovery

Marked and rapid effects of pharmacological HIF-2α antagonism on hypoxic ventilatory control

(2020) Xiaotong Cheng et al.   JOURNAL OF CLINICAL INVESTIGATION

Phase II study of the oral HIF-2α inhibitor MK-6482 for Von Hippel-Lindau disease–associated renal cell carcinoma.

(2020) Eric Jonasch et al.   JOURNAL OF CLINICAL ONCOLOGY

Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma

(2020) David A. Braun et al.   NATURE MEDICINE

Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

(2019) Robert J. Motzer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

(2019) Brian I. Rini et al.   NEW ENGLAND JOURNAL OF MEDICINE

Results from a phase I expansion cohort of the first-in-class oral HIF-2α inhibitor PT2385 in combination with nivolumab in patients with previously treated advanced RCC.

(2019) Brian I. Rini et al.   JOURNAL OF CLINICAL ONCOLOGY

First-line pembrolizumab (pembro) monotherapy in advanced clear cell renal cell carcinoma (ccRCC): Updated results for KEYNOTE-427 cohort A.

(2019) Scott S. Tykodi et al.   JOURNAL OF CLINICAL ONCOLOGY

Safety and activity of a first-in-class oral HIF2-alpha inhibitor, PT2385, in patients with first recurrent glioblastoma (GBM).

(2019) Roy E. Strowd et al.   JOURNAL OF CLINICAL ONCOLOGY

Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial

(2019) Brian I Rini et al.   LANCET

A CRISPR-Cas9 delivery system for in vivo screening of genes in the immune system

(2019) Martin W. LaFleur et al.   Nature Communications

Targeting mTOR for cancer therapy

(2019) Hui Hua et al.   Journal of Hematology & Oncology

3-[(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yl]oxy-5-fluorobenzonitrile (PT2977), a Hypoxia-Inducible Factor 2α (HIF-2α) Inhibitor for the Treatment of Clear Cell Renal Cell Carcinoma

(2019) Rui Xu et al.   JOURNAL OF MEDICINAL CHEMISTRY

HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species

(2019) Hilary E. Nicholson et al.   Science Signaling

912PDResults of the phase II TRAXAR study: A randomized phase II trial of axitinib and TRC105 (TRAX) versus axitinib (AX) alone in patients with advanced or metastatic renal cell carcinoma (mRCC)

(2019) T K Choueiri et al.   ANNALS OF ONCOLOGY

Biologists who decoded how cells sense oxygen win medicine Nobel

(2019) Heidi Ledford et al.   NATURE

TBK1 Is a Synthetic Lethal Target in Cancer with VHL Loss

(2019) Lianxin Hu et al.   Cancer Discovery

Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update

(2018) Toni K. Choueiri et al.   EUROPEAN JOURNAL OF CANCER

Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma

(2018) Kevin D. Courtney et al.   JOURNAL OF CLINICAL ONCOLOGY

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma

(2018) Robert J. Motzer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Hypoxia-inducible factor 2α: a novel target in gliomas

(2018) Jaclyn J Renfrow et al.   Future Medicinal Chemistry

A first-in-human phase 1 dose-escalation trial of the oral HIF-2a inhibitor PT2977 in patients with advanced solid tumors.

(2018) Kyriakos P. Papadopoulos et al.   JOURNAL OF CLINICAL ONCOLOGY

Fundamental Mechanisms of Immune Checkpoint Blockade Therapy

(2018) Spencer C. Wei et al.   Cancer Discovery

Endogenous retroviral signatures predict immunotherapy response in clear cell renal cell carcinoma

(2018) Christof C. Smith et al.   JOURNAL OF CLINICAL INVESTIGATION

Evolving Systemic Treatment Landscape for Patients With Advanced Renal Cell Carcinoma

(2018) Rana R. McKay et al.   JOURNAL OF CLINICAL ONCOLOGY

Prognostication in Kidney Cancer: Recent Advances and Future Directions

(2018) Jeffrey Graham et al.   JOURNAL OF CLINICAL ONCOLOGY

Design and Activity of Specific Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of Clinical Candidate (S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385)

(2018) Paul M. Wehn et al.   JOURNAL OF MEDICINAL CHEMISTRY

Fibroblast growth factor receptors as treatment targets in clinical oncology

(2018) Masaru Katoh   Nature Reviews Clinical Oncology

Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study

(2018) Asim Amin et al.   Journal for ImmunoTherapy of Cancer

Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial

(2017) Toni K. Choueiri et al.   JOURNAL OF CLINICAL ONCOLOGY

Systemic Therapy for Metastatic Renal-Cell Carcinoma

(2017) Toni K. Choueiri et al.   NEW ENGLAND JOURNAL OF MEDICINE

Tumor Mutational Burden and Response Rate to PD-1 Inhibition

(2017) Mark Yarchoan et al.   NEW ENGLAND JOURNAL OF MEDICINE

No reason to reconsider HIF-2 as an oncogene in neuroblastoma and other cancer forms

(2017) Sofie Mohlin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase

(2017) Abhishek A. Chakraborty et al.   Science Translational Medicine

Axl inhibition induces the antitumor immune response which can be further potentiated by PD-1 blockade in the mouse cancer models

(2017) Zhiqiang Guo et al.   Oncotarget

Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression

(2017) Aly-Khan A. Lalani et al.   Oncotarget

A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma

(2016) Eli M. Wallace et al.   CANCER RESEARCH

The DART Study: Results from the Dose-Escalation and Expansion Cohorts Evaluating the Combination of Dalantercept plus Axitinib in Advanced Renal Cell Carcinoma

(2016) Martin H. Voss et al.   CLINICAL CANCER RESEARCH

A Randomised Phase 2 Study of AZD2014 Versus Everolimus in Patients with VEGF-Refractory Metastatic Clear Cell Renal Cancer

(2016) Thomas Powles et al.   EUROPEAN UROLOGY

Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma

(2016) Thomas Powles et al.   JOURNAL OF CLINICAL ONCOLOGY

Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma

(2016) Robert J Motzer et al.   LANCET ONCOLOGY

Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial

(2016) Toni K Choueiri et al.   LANCET ONCOLOGY

Targeting renal cell carcinoma with a HIF-2 antagonist

(2016) Wenfang Chen et al.   NATURE

On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models

(2016) Hyejin Cho et al.   NATURE

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

(2016) J M Thompson et al.   ONCOGENE

A Phase Ib Study of BEZ235, a Dual Inhibitor of Phosphatidylinositol 3-Kinase (PI3K) and Mammalian Target of Rapamycin (mTOR), in Patients With Advanced Renal Cell Carcinoma

(2016) Maria I. Carlo et al.   ONCOLOGIST

Pre-clinical evaluation of AZD-2014, a novel mTORC1/2 dual inhibitor, against renal cell carcinoma

(2015) Bing Zheng et al.   CANCER LETTERS

BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma—A Trial of the ECOG–ACRIN Cancer Research Group (E2804)

(2015) Keith T. Flaherty et al.   JOURNAL OF CLINICAL ONCOLOGY

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

(2015) Robert J. Motzer et al.   JOURNAL OF CLINICAL ONCOLOGY

Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial

(2015) Robert J Motzer et al.   LANCET ONCOLOGY

Structural integration in hypoxia-inducible factors

(2015) Dalei Wu et al.   NATURE

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

(2015) Toni K. Choueiri et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

(2015) Robert J. Motzer et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma

(2015) L Zhou et al.   ONCOGENE

Emerging strategies to overcome the resistance to current mTOR inhibitors in renal cell carcinoma

(2014) Matteo Santoni et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

TGF-β& BMP Receptors Endoglin and ALK1: Overview of their Functional Role and Status as Antiangiogenic Targets

(2014) Leon Jonker   MICROCIRCULATION

Combination Strategy Targeting VEGF and HGF/c-met in Human Renal Cell Carcinoma Models

(2014) E. Ciamporcero et al.   MOLECULAR CANCER THERAPEUTICS

Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

(2014) Marco Gerlinger et al.   NATURE GENETICS

Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET

(2014) Erinn B. Rankin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC)

(2013) Ana M. Molina et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Transcriptional regulation by hypoxia inducible factors

(2013) Veronica L. Dengler et al.   CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY

A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: Final overall survival results and safety update

(2013) Cora N. Sternberg et al.   EUROPEAN JOURNAL OF CANCER

Development of Inhibitors of the PAS-B Domain of the HIF-2α Transcription Factor

(2013) Jamie L. Rogers et al.   JOURNAL OF MEDICINAL CHEMISTRY

Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial

(2013) Robert J Motzer et al.   LANCET ONCOLOGY

Comprehensive molecular characterization of clear cell renal cell carcinoma

(2013)   NATURE

Allosteric inhibition of hypoxia inducible factor-2 with small molecules

(2013) Thomas H Scheuermann et al.   Nature Chemical Biology

Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma

(2013) Robert J. Motzer et al.   NEW ENGLAND JOURNAL OF MEDICINE

AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney

(2012) Brian Rini et al.   CANCER

An oxygen-regulated switch in the protein synthesis machinery

(2012) James Uniacke et al.   NATURE

Common genetic variants at the 11q13.3 renal cancer susceptibility locus influence binding of HIF to an enhancer of cyclin D1 expression

(2012) Johannes Schödel et al.   NATURE GENETICS

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

(2012) Marco Gerlinger et al.   NEW ENGLAND JOURNAL OF MEDICINE

Renal Tubular HIF-2α Expression Requires VHL Inactivation and Causes Fibrosis and Cysts

(2012) Ruth E. Schietke et al.   PLoS One

Suppression of Tumor Invasion and Metastasis by Concurrent Inhibition of c-Met and VEGF Signaling in Pancreatic Neuroendocrine Tumors

(2012) Barbara Sennino et al.   Cancer Discovery

Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial

(2011) Brian I Rini et al.   LANCET

Cabozantinib (XL184), a Novel MET and VEGFR2 Inhibitor, Simultaneously Suppresses Metastasis, Angiogenesis, and Tumor Growth

(2011) F. M. Yakes et al.   MOLECULAR CANCER THERAPEUTICS

Inactivation of the von Hippel–Lindau tumor suppressor leads to selective expression of a human endogenous retrovirus in kidney cancer

(2011) E Cherkasova et al.   ONCOGENE

Development of Second-Generation VEGFR Tyrosine Kinase Inhibitors: Current Status

(2011) Pankaj Bhargava et al.   Current Oncology Reports

Genetic and Functional Studies Implicate HIF1  as a 14q Kidney Cancer Suppressor Gene

(2011) C. Shen et al.   Cancer Discovery

VHL-gene Deletion in Single Renal Tubular Epithelial Cells and Renal Tubular Cysts: Further Evidence for a Cyst-dependent Progression Pathway of Clear Cell Renal Carcinoma in von Hippel-Lindau Disease

(2010) Matteo Montani et al.   AMERICAN JOURNAL OF SURGICAL PATHOLOGY

HGF/c-Met Acts as an Alternative Angiogenic Pathway in Sunitinib-Resistant Tumors

(2010) F. Shojaei et al.   CANCER RESEARCH

The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 Compared with Rapamycin in Renal Cell Carcinoma

(2010) D. C. Cho et al.   CLINICAL CANCER RESEARCH

A complex task? Direct modulation of transcription factors with small molecules

(2010) Angela N Koehler   CURRENT OPINION IN CHEMICAL BIOLOGY

Phase III Trial of Bevacizumab Plus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma (AVOREN): Final Analysis of Overall Survival

(2010) Bernard Escudier et al.   JOURNAL OF CLINICAL ONCOLOGY

Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial

(2010) Cora N. Sternberg et al.   JOURNAL OF CLINICAL ONCOLOGY

Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3

(2010) Mark P Purdue et al.   NATURE GENETICS

Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney

(2009) R. Beroukhim et al.   CANCER RESEARCH

Phase I Trial of Bevacizumab Plus Escalated Doses of Sunitinib in Patients With Metastatic Renal Cell Carcinoma

(2009) Darren R. Feldman et al.   JOURNAL OF CLINICAL ONCOLOGY

Sorafenib for Treatment of Renal Cell Carcinoma: Final Efficacy and Safety Results of the Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial

(2009) Bernard Escudier et al.   JOURNAL OF CLINICAL ONCOLOGY

Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma

(2009) Robert J. Motzer et al.   JOURNAL OF CLINICAL ONCOLOGY

A Feedback Loop Involving the Phd3 Prolyl Hydroxylase Tunes the Mammalian Hypoxic Response In Vivo

(2009) Y. A. Minamishima et al.   MOLECULAR AND CELLULAR BIOLOGY

Characterization of Rictor Phosphorylation Sites Reveals Direct Regulation of mTOR Complex 2 by S6K1

(2009) C. C. Dibble et al.   MOLECULAR AND CELLULAR BIOLOGY

Regulation of endocytosis via the oxygen-sensing pathway

(2009) Yi Wang et al.   NATURE MEDICINE

Artificial ligand binding within the HIF2  PAS-B domain of the HIF2 transcription factor

(2009) T. H. Scheuermann et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

High‐dose interleukin‐2 for the treatment of metastatic renal cell carcinoma

(2008) Jacob A. Klapper et al.   CANCER

HIF-α Effects on c-Myc Distinguish Two Subtypes of Sporadic VHL-Deficient Clear Cell Renal Carcinoma

(2008) John D. Gordan et al.   CANCER CELL

Differential Dependence of Hypoxia-inducible Factors 1α and 2α on mTORC1 and mTORC2

(2008) Alfredo Toschi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells

(2008) Yoshiyuki Takahashi et al.   JOURNAL OF CLINICAL INVESTIGATION

Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial

(2008) Robert J Motzer et al.   LANCET

Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase Pathway

(2008) William G. Kaelin et al.   MOLECULAR CELL

Kinase requirements in human cells: III. Altered kinase requirements in VHL-/- cancer cells detected in a pilot synthetic lethal screen

(2008) A. Bommi-Reddy et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA