Eric Jonasch

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (151)740.37 Total impact

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    Dataset: MCO
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    ABSTRACT: The phosphatidylinositol 3 kinase (PI3K)/AKT pathway is genetically targeted in more pathway components and in more tumor types than any other growth factor signaling pathway, and thus is frequently activated as a cancer driver. More importantly, the PI3K/AKT pathway is composed of multiple bifurcating and converging kinase cascades, providing many potential targets for cancer therapy. Renal cell carcinoma (RCC) is a high-risk and high-mortality cancer that is notoriously resistant to traditional chemotherapies or radiotherapies. The PI3K/AKT pathway is modestly mutated but highly activated in RCC, representing a promising drug target. Indeed, PI3K pathway inhibitors of the rapalog family are approved for use in RCC. Recent large-scale integrated analyses of a large number of patients have provided a molecular basis for RCC, reiterating the critical role of the PI3K/AKT pathway in this cancer. In this review, we summarizes the genetic alterations of the PI3K/AKT pathway in RCC as indicated in the latest large-scale genome sequencing data, as well as treatments for RCC that target the aberrant activated PI3K/AKT pathway.
    Journal of Genetics and Genomics 03/2015; DOI:10.1016/j.jgg.2015.03.003 · 2.92 Impact Factor
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    ABSTRACT: Comparing prognostic factors for overall survival (OS) in community-practice metastatic renal cell carcinoma (mRCC) patients receiving second-line everolimus with those previously reported in clinical trials. Two separate chart sets (2009 - 2012) were used to develop and validate a prognostic model for patients initiating second-line everolimus after first-line tyrosine kinase inhibitor (TKI). Prognostic factors for OS have been identified and validated in separate samples. One-year OS probabilities in the study (n = 220) and validation (n = 97) samples were 68 and 67%; median OS was 19 and 23 months - higher than the 1-year OS of 60% and median OS of 14.8 months of RECORD-1. Karnofsky performance score < 80%, duration of mRCC < 1 year, progression on first-line TKI, liver metastasis and clear cell histology were significant prognostic factors for shorter survival. One-year OS estimates were 84% for validation sample patients with 0 - 2 risk factors, 63% for 3 risk factors and 22% for 4 - 5 risk factors (log-rank p < 0.001). Real-world prognostic factors for OS following second-line everolimus for mRCC were largely consistent with those previously identified in trial data; however, OS was longer in the practice setting than in clinical trials and was not associated with type of first-line TKI.
    Expert Opinion on Pharmacotherapy 03/2015; DOI:10.1517/14656566.2015.1020298 · 3.09 Impact Factor
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    ABSTRACT: Isolated local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) for renal cell carcinoma (RCC) poses a therapeutic challenge. We investigated the outcomes of patients with localized RPR treated with surgical resection. This was a retrospective single-institutional study of 102 patients with RPR treated with surgery from 1990-2014. Demographics, clinical and pathological features, location of RPR, perioperative complications were reported using descriptive statistics. Recurrence free survival (RFS) and cancer-specific survival (CSS) were studied using univariate and multivariate analyses. Median age at RPR diagnosis was 55 years (IQR 49-64). Sixty-two (60.8%) patients were pT3-4 and 20 (19.6%) were pN1. No patients had distant metastatic disease at time of RPR surgery. Median time from nephrectomy to RPR diagnosis was 19 months (IQR 5-38.8). The median size of resected RPR was 4.5cm (IQR 2.7-7). Median follow up after RPR surgery was 32 months (IQR 16-57). Metastatic progression was observed in 60 (58.8%) patients after RPR surgery. Neoadjuvant and salvage systemic therapy were administered in 46 (45.1%) and 48 (47.1%) patients, respectively. On multivariate analysis, pathological nodal stage at original nephrectomy and maximum diameter of RPR were identified as independent risk factors for cancer specific death. Clinico-pathological factors at the time of nephrectomy as well as RPR surgery are important prognosticators. Aggressive surgical resection offers potential cure in a substantial number of patients with RPR with acceptable complications, and still plays a dominant role in the management of isolated locally recurrent RCC. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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    ABSTRACT: Objective The purpose of this study was to examine the prevalence of posttraumatic stress symptoms (PTSS) in patients with renal cell carcinoma (RCC), the associations and co-occurrence between PTSS, depressive, and other cancer-related symptoms and the ability of a single-item distress question to identify patients with PTSS.Methods Patients with stage I-IV RCC completed assessments of depressive symptoms (Center for Epidemiologic Studies Depression Scale), PTSS (Impact of Event Scale), cancer-related symptoms (MD Anderson Symptom Inventory), fatigue (Brief Fatigue Inventory), and sleep disturbance (Pittsburgh Sleep Quality Index). We used the distress item on the MD Anderson Symptom Inventory as a distress screener and general linear model analyses to test study hypotheses.ResultsOf the 287 patients (29% stage IV; 42% female; mean age = 58 years), 46% (n = 131) reported psychiatric symptoms with 15% (n = 44) reporting comorbid clinical levels of depressive symptoms and PTSS, 24% (n = 70) PTSS alone, and 6% (n = 17) depressive symptoms alone. Controlling for age, gender, and stage, patients with comorbid depressive symptoms and PTSS reported more cancer-related symptoms (p < 0.0001), fatigue (p < 0.0001), and sleep disturbance (p = 0.0003) than those with PTSS alone and more cancer-related symptoms (p = 0.002) and fatigue (p = 0.09) than those with depressive symptoms alone. Sensitivity analyses revealed that 26.9% of negative cases on the distress item fell within the clinical range of the Impact of Event Scale and 9.3% of negative cases met caseness on the Center for Epidemiologic Studies Depression Scale.Conclusions Posttraumatic stress symptoms occurred both independently and comorbid with depressive symptoms in patients with RCC. PTSS were correlated with overall cancer symptom burden. Single-item distress screening was less sensitive in detecting PTSS than depressive symptoms. Therefore, additional screening strategies are required in the clinical setting.
    Psycho-Oncology 02/2015; DOI:10.1002/pon.3758 · 4.04 Impact Factor
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    ABSTRACT: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. Although existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate postnephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease. An institutional review board-approved review from 1986 to 2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy, and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses. OS for the entire cohort (n = 77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who has NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and recurrence-free survival. Limitations include the retrospective nature of this study and relatively small sample size. Long-term survival for patients with sRCC, even in clinically localized disease, is poor. Aggressive surveillance of those who have NED following nephrectomy is essential, and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.
    Urologic Oncology 02/2015; DOI:10.1016/j.urolonc.2014.11.021 · 3.36 Impact Factor
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    ABSTRACT: Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer, and anti-angiogenic therapy is the current mainstay of treatment. RCC patients develop innate or adaptive resistance to anti-angiogenic therapy. There is a need to identify biomarkers which predict therapeutic resistance and guide combination therapy. Methods: Tissue microarrays with triplicate cores for each case were generated from 33 unaffected kidneys, 41 untreated primary RCC, and 42 bevacizumab and 39 sunitinib pretreated primary RCC from patients with metastatic RCC. Immunohistochemistry was used to visualize immune cell infiltration. Staining quantitation was performed using a Vectra multispectral system. Statistical analysis was performed using unpaired Student´s t-test. Results: We assessed the interaction between anti-angiogenic therapy and tumor immune microenvironment, and determined their impact on clinical outcome. Here we found that anti-angiogenic therapy treated RCC primary tumors demonstrated increased infiltration of CD4+ and CD8+ T lymphocytes, which was inversely related to patient survival. Furthermore, anti-angiogenic therapy treated specimens showed higher infiltration of CD4+FOXP3+regulatory T cells (Tregs) and enhanced expression of checkpoint ligand programed death-ligand 1 (PD-L1). Both immunosuppressive features were correlated with T lymphocyte infiltration and were negatively related to patient overall survival (OS) and/or progression free survival (PFS). Treatment of RCC cell lines and RCC xenografts in immunodeficient mice with sunitinib also increased tumor PD-L1 expression. Conclusions: This study indicates that anti-angiogenic treatment may both positively and negatively regulate the tumor immune microenvironment. These findings generate hypotheses on resistance mechanisms to antiangiogenic therapy, and will guide the development of combination therapy with PD-1/PD-L1 blocking agents.
    2015 Genitourinary Cancers Symposium of the American Society of Clinical Oncology, J Clin Oncol 33, 2015 (suppl 7; abstr 419); 02/2015
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    ABSTRACT: The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These NCCN Guidelines Insights highlight the recent updates/changes in these guidelines, and updates include axitinib as first-line treatment option for patients with clear cell renal carcinoma, new data to support pazopanib as subsequent therapy for patients with clear cell carcinoma after first-line treatment with another tyrosine kinase inhibitor, and guidelines for follow-up of patients with renal cell carcinoma. Copyright © 2015 by the National Comprehensive Cancer Network.
    Journal of the National Comprehensive Cancer Network: JNCCN 02/2015; 13(2):151-9. · 4.24 Impact Factor
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    Sarathi Kalra, Brian Rini, Eric Jonasch
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    ABSTRACT: Sunitinib malate is an oral multi-targeted tyrosine kinase inhibitor exhibiting antiangiogenic activity. Sunitinib demonstrated improved outcomes in comparison to interferon alpha (IFN-in a large phase III study of treatment naïve patients with metastatic renal cell carcinoma (mRCC). Maintaining patients on sunitinib treatment is essential for a sustained disease control as higher exposure to sunitinib has been associated with an improved overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Various studies have compared the outcomes of patients undergoing sunitinib therapy based on modifications from their standard dose and schedule. Several studies have shown that switching to an alternate schedule with more frequent dose interruptions without affecting dose density over a six-week cycle is associated with improved outcomes and increased tolerability. Keywords: sunitinib; renal cell carcinoma; drug administration schedule; alternate schedule.
    Annals of Oncology 01/2015; DOI:10.1093/annonc/mdv030 · 6.58 Impact Factor
  • Sarathi Kalra, Eric Jonasch
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    ABSTRACT: The ErbB family of receptor tyrosine kinases comprises of epidermal growth factor (EGF) receptor (HER1/ErbB1), HER2/neu (ErbB2), HER3 (ErbB3), and HER4 (ErbB4). Interaction of ErbB receptors with a ligand leads to formation of higher-order aggregates which may form signaling platforms in the plasma membrane. ErbB2 is the only receptor which doesn’t need a ligand for activation. Various molecules have been developed which block ErbB signaling by either generating antibodies against the extracellular domain of the EGF receptor or directly inhibiting ErbB1/EGF signaling. The relevance of the ErbB family of receptors as actionable targets in renal cell carcinoma is a topic of debate. Some of the recently developed drugs that are discussed in this chapter and have been studied in renal cell carcinoma are cetuximab, panitumumab, gefitinib, erlotinib, and lapatinib. These agents have failed to demonstrate consistent clinical benefit in patients with advanced renal cell carcinoma and are currently not considered standard treatment in this disease.
    Renal Cell Carcinoma: Molecular Targets and Clinical Applications, 3 edited by Bukowski Ronald M, Figlin Robert A, Motzer Robert, 01/2015: chapter 14: pages 285-302; Springer., ISBN: 978-1-4939-1622-1
  • Sarathi Kalra, Eric Jonasch
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    ABSTRACT: Comprising only a small fraction of all renal tumors, inherited renal cell carcinomas (RCC) have provided great insight into the molecular biology of RCC. The first genetic evidence for the hereditary nature of RCC was from the discovery of von Hippel-Lindau gene. Unlike sporadic cancers, inherited RCCs are usually bilateral and multiple and they develop at a younger age. Inherited variants having an increased risk for RCC include von Hippel-Lindau (VHL) disease, Birt-Hogg-Dube (BHD) syndrome, hereditary papillary renal cell carcinoma (HPRC), hereditary leiomyomatosis and renal cell carcinoma (HLRCC), and tuberous sclerosis (TS)
    Renal Cell Carcinoma, First edited by Nizar M Tannir, 12/2014: chapter Inherited Renal Cell Carcinomas: pages 27-36; Oxford University Press., ISBN: 978-0-19-998813-6
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    ABSTRACT: Clear cell kidney cancer (CRCC) is initiated typically by loss of the tumor suppressor VHL, driving constitutive activation of HIF-1 and HIF-2. However, whereas HIF-1 has a tumor suppressor role, HIF-2 plays a distinct role in driving CRCC. In this study, we show that the HIF-1α E3 ligase HAF complexes with HIF-2α at DNA to promote HIF-2-dependent transcription through a mechanism relying upon HAF SUMOylation. HAF SUMOylation was induced by hypoxia, whereas HAF-mediated HIF-1α degradation was SUMOylation independent. HAF overexpression in mice increased CRCC growth and metastasis. Clinically, HAF overexpression was associated with poor prognosis. Taken together, our results show that HAF is a specific mediator of HIF-2 activation that is critical for CRCC development and morbidity. Copyright © 2014, American Association for Cancer Research.
    Cancer Research 11/2014; 75(2). DOI:10.1158/0008-5472.CAN-13-2190 · 9.28 Impact Factor
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    ABSTRACT: Clinical trials have demonstrated that pazopanib prolongs progression-free survival (PFS), with an acceptable safety profile, in patients with advanced renal cell carcinoma (aRCC). The efficacy of second-line mTOR inhibitors in pazopanib-treated patients has also been evaluated in clinical trials; however, few studies have evaluated first-line pazopanib or second-line mTOR inhibitors in real-world settings. This study evaluated outcomes of first-line pazopanib, and pazopanib followed by mTOR inhibitors, in a community oncology setting.Patients and Methods This was a retrospective analysis of eligible patients in US Oncology’s iKnowMed electronic health records database who were treated for aRCC between November 1, 2009, and August 31, 2012. Patients received first-line therapy with pazopanib (Cohort 1), followed by second-line therapy with either everolimus or temsirolimus (Cohort 2). Key outcomes included overall survival (OS), PFS, adverse events (AEs), treatment patterns, and healthcare resource use.ResultsMedian OS in Cohort 1 (n=177) was 22 months; median PFS was 8.5 months. The most common AEs were fatigue (56%), diarrhea (52%), vomiting (44%), and nausea (40%). Median persistence was 151 days with pazopanib. Median OS in Cohort 2 (n=35) was 16 months; median PFS was 5.7 months. The most common AEs were fatigue (51%) and nausea (34%). Median persistence was 93 days with everolimus and 49 days with temsirolimus.Conclusion Outcomes in patients treated with first-line pazopanib in this community setting were consistent with previous prospective and retrospective studies. Although the second-line cohort was small, results of mTOR inhibitors after pazopanib were also consistent with previous observations.
    Clinical Genitourinary Cancer 11/2014; DOI:10.1016/j.clgc.2014.11.001 · 1.69 Impact Factor
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    ABSTRACT: The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15 years. Progress in the surgical management of the primary tumor and increased understanding of the molecular biology and genomics of the disease have led to the development of new therapeutic agents. The management of the primary tumor has changed owing to the realization that clean margins around the primary lesion are sufficient to prevent local recurrence, as well as the development of more sophisticated tools and techniques that increase the safety of partial nephrectomy. The management of advanced disease has altered even more dramatically as a result of new agents that target the tumor vasculature or that attenuate the activation of intracellular oncogenic pathways. This review summarizes data from prospective randomized phase III studies on the surgical management and systemic treatment of RCC, and provides an up to date summary of the histology, genomics, staging, and prognosis of RCC. It describes the management of the primary tumor and offers an overview of systemic agents that form the mainstay of treatment for advanced disease. The review concludes with an introduction to the exciting new class of immunomodulatory agents that are currently in clinical trials and may form the basis of a new therapeutic approach for patients with advanced RCC.
    BMJ Clinical Research 11/2014; 349:g4797. DOI:10.1136/bmj.g4797 · 14.09 Impact Factor
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    ABSTRACT: Our recent study shows that autophagy collaborates with proteasomes to degrade endothelial PAS domaincontaining protein 1 (EPAS1, also known as HIF2a) in a manner dependent on Von Hippel-Lindau (VHL) and sequestosome 1 (SQSTM1/p62). The genetic dysregulation of autophagy is a common feature of different subtypes of renal cell carcinoma (RCC).
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    ABSTRACT: Introduction Limited data are available regarding patients with RCC and ESRD treated with targeted therapies (TTs). The objective of this study was to explore the tolerability and safety of TT in patients with metastatic renal cell carcinoma (mRCC) and end stage renal disease (ESRD). Methods We retrospectively indentified patients with mRCC and ESRD treated at the University of Texas MD Anderson Cancer Center from 2002-2012. Patients’ characteristics including demographics, histology, treatment, and adverse events (AEs) are reported. Time on treatment (TOT) was determined from date of drug initiation to discontinuation. Overall survival (OS) was determined from initiation of TT to death. Statistics are descriptive. Results Fourteen patients were identified. Ten patients had clear cell histology and 4 had papillary histology. The median number of TTs per patient was 3 (range 1-4) with median TOT of 28 months for all TT. Eighty-eight percent of all toxicities were grade 1-2; no grade 4 toxicities were noted. Treatment discontinuations included 3 patients treated with sorafenib due to hand-foot syndrome, intolerable fatigue, and squamous cell skin cancer development; 2 patients treated with pazopanib due to intolerable fatigue and increased transaminases; and 1 patient treated with everolimus due to pneumonitis . Eight patients died of progressive disease. Median OS from initiation of TT was 28.5 months and 35 months from time of diagnosis. Conclusions Toxicities were mild to moderate and consistent with those reported in previous studies. TTs appear to be safe, well tolerated and produce anti-tumor response in patients with mRCC and end-stage renal disease on dialysis.
    Clinical Genitourinary Cancer 10/2014; 12(5). DOI:10.1016/j.clgc.2014.01.004 · 1.69 Impact Factor
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    ABSTRACT: Clear cell papillary renal cell carcinoma (CCPRCC) is a renal neoplasm that has recently received widespread recognition in the literature. There have been several reports of this tumor arising in a sporadic setting and in patients with end-stage renal disease; however, there is limited information available about the clinical, pathologic, and genetic characteristics of this tumor in the setting of Von Hippel-Lindau (VHL) disease. We herein report a series of three patients that developed CCPRCC in this unique clinical setting. The histology and immunohistochemical profile for all three cases was similar to that which has been previously reported for CCPRCC. All tumors were diffusely and strongly positive for Cytokeratin 7, negative for alpha methyl Co-A racemase and showed at least focal staining for CD10. Comparative genomic analysis was performed on tumors from all three patients. One tumor demonstrated monosomy 3 and the other two tumors showed normal chromosomal content. All three patients were alive without evidence of disease progression 5, 3 and 3 years after surgery. CCPRCC represents a distinct tumor type that may occur in the setting of VHL disease and should be considered in the differential diagnosis of extensively cystic renal tumors arising in this clinical setting. Molecular analysis in our series of cases suggests that CCPRCC does indeed represent a unique histologic subtype and must be distinguished from clear cell renal cell carcinoma (CCRCC) due to different biologic potentials. Ancillary studies for accurate classification are recommended due to significant morphologic overlap with CCRCC.
    Human pathology 09/2014; 45(9). DOI:10.1016/j.humpath.2014.06.004 · 2.81 Impact Factor
  • Thai H Ho, Eric Jonasch
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    ABSTRACT: Hereditary forms of renal cell carcinoma (RCC) have yielded clues regarding the molecular pathogenesis of sporadic RCC. The discovery of germline mutations in chromatin-modulating enzymes also defined a new hereditary RCC syndrome. Although histologically distinct RCC subtypes exist, emerging themes shared between hereditary and sporadic RCC include dysregulation of the von Hippel-Lindau tumor suppressor protein/hypoxia inducible factor axis, defective ciliogenesis, and aberrant tumor metabolism. This article describes the most common hereditary RCC syndromes and associated extrarenal manifestations. Recent evidence supports developing screening guidelines for early-onset RCC to identify persons with germline mutations in the absence of secondary clinical manifestations.
    Journal of the National Comprehensive Cancer Network: JNCCN 09/2014; 12(9):1347-1355. · 4.24 Impact Factor
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    ABSTRACT: Abstract Background: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study compares the effectiveness of these therapies in a multi-practice chart review and synthesizes the findings with those of a similarly-designed study. Methods: Medical oncologists/hematologists (N=36) were recruited to review charts for patients aged ≥ 18 years, received a 1st-line TKI and initiated 2nd-line targeted therapy in 2010 or later. The primary outcome was time from 2nd-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving 2nd-line everolimus (EVE), temsirolimus (TEM), or TKI as a class, using a Cox proportional hazards model adjusting for type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled, in a meta-analysis, with previously-reported HRs for progression-free survival from a chart review with a similar design. Results: A total of 138, 64 and 79 patients received 2nd-line therapy with EVE, TEM or a TKI, respectively. Adjusting for baseline characteristics, EVE was associated with numerical, but not statistically significant, reductions of 28% (HR=0.72, 95% CI [0.45, 1.16]) and 26% (HR=0.74, 95% CI [0.48, 1.15]) in the hazard of TTF compared to TEM and TKI, respectively. After pooling the HRs from both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (HR=0.73, 95%CI [0.57, 0.93], and HR=0.75, 95%CI [0.57, 0.98], respectively). Limitations: Limitations include retrospective analyses with possible missing or erroneous chart data, confounding of unobserved factors due to non-randomization, and limited data for axitinib during the study period. Conclusions: In pooled results from two independent multi-practice chart reviews of 2nd-line mRCC treatment, EVE was associated with significantly reduced hazards of treatment failure compared to TEM and to TKIs as a class.
    Current Medical Research and Opinion 08/2014; 30(11):1-30. DOI:10.1185/03007995.2014.949645 · 2.37 Impact Factor
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    ABSTRACT: Autophagy is a conserved process involved in lysosomal degradation of protein aggregates and damaged organelles. The role of autophagy in cancer is a topic of intense debate, and the underlying mechanism is still not clear. The hypoxia-inducible factor 2α (HIF2α), an oncogenic transcription factor implicated in renal tumorigenesis, is known to be degraded by the ubiquitin-proteasome system (UPS). Here, we report that HIF2α is in part constitutively degraded by autophagy. HIF2α interacts with autophagy-lysosome system components. Inhibition of autophagy increases HIF2α, whereas induction of autophagy decreases HIF2α. The E3 ligase von Hippel-Lindau and autophagy receptor protein p62 are required for autophagic degradation of HIF2α. There is a compensatory interaction between the UPS and autophagy in HIF2α degradation. Autophagy inactivation redirects HIF2α to proteasomal degradation, whereas proteasome inhibition induces autophagy and increases the HIF2α-p62 interaction. Importantly, clear-cell renal cell carcinoma (ccRCC) is frequently associated with monoallelic loss and/or mutation of autophagy-related gene ATG7, and the low expression level of autophagy genes correlates with ccRCC progression. The protein levels of ATG7 and beclin 1 are also reduced in ccRCC tumors. This study indicates that autophagy has an anticancer role in ccRCC tumorigenesis, and suggests that constitutive autophagic degradation of HIF2α is a novel tumor suppression mechanism.Oncogene advance online publication, 7 July 2014; doi:10.1038/onc.2014.199.
    Oncogene 07/2014; DOI:10.1038/onc.2014.199 · 8.56 Impact Factor

Publication Stats

2k Citations
740.37 Total Impact Points


  • 2004–2015
    • University of Texas MD Anderson Cancer Center
      • • Genitourinary Medical Oncology
      • • Department of General Oncology
      • • Department of Systems Biology
      • • Department of Molecular Therapeutics
      Houston, Texas, United States
  • 2013
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
    • American Urological Association
      Linthicum, Maryland, United States
  • 2011
    • University of California, San Diego
      San Diego, California, United States
  • 2005–2011
    • University of Houston
      Houston, Texas, United States
    • Thomas Jefferson University
      • Department of Pathology, Anatomy & Cell Biology
      Filadelfia, Pennsylvania, United States
  • 2001
    • Massachusetts General Hospital
      Boston, Massachusetts, United States