Cancers

Research

Jump to: Review

24 pages, 3931 KiB

Open AccessArticle

Artesunate Inhibits Growth of Sunitinib-Resistant Renal Cell Carcinoma Cells through Cell Cycle Arrest and Induction of Ferroptosis

by Sascha D. Markowitsch, Patricia Schupp, Julia Lauckner, Olesya Vakhrusheva, Kimberly S. Slade, René Mager, Thomas Efferth, Axel Haferkamp and Eva Juengel

Cancers 2020, 12(11), 3150; https://doi.org/10.3390/cancers12113150 - 27 Oct 2020

Cited by 86 | Viewed by 4877

Abstract

Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to [...] Read more.

Although innovative therapeutic concepts have led to better treatment of advanced renal cell carcinoma (RCC), efficacy is still limited due to the tumor developing resistance to applied drugs. Artesunate (ART) has demonstrated anti-tumor effects in different tumor entities. This study was designed to investigate the impact of ART (1–100 µM) on the sunitinib-resistant RCC cell lines, Caki-1, 786-O, KTCTL26, and A-498. Therapy-sensitive (parental) and untreated cells served as controls. ART’s impact on tumor cell growth, proliferation, clonogenic growth, apoptosis, necrosis, ferroptosis, and metabolic activity was evaluated. Cell cycle distribution, the expression of cell cycle regulating proteins, p53, and the occurrence of reactive oxygen species (ROS) were investigated. ART significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant RCC cells. In Caki-1, 786-O, and A-498 cell lines growth inhibition was associated with G0/G1 phase arrest and distinct modulation of cell cycle regulating proteins. KTCTL-26 cells were mainly affected by ART through ROS generation, ferroptosis, and decreased metabolism. p53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Graphical abstract

15 pages, 996 KiB

Open AccessArticle

Exploratory Pilot Study of Circulating Biomarkers in Metastatic Renal Cell Carcinoma

by Ilaria Grazia Zizzari, Chiara Napoletano, Alessandra Di Filippo, Andrea Botticelli, Alain Gelibter, Fabio Calabrò, Ernesto Rossi, Giovanni Schinzari, Federica Urbano, Giulia Pomati, Simone Scagnoli, Aurelia Rughetti, Salvatore Caponnetto, Paolo Marchetti and Marianna Nuti

Cancers 2020, 12(9), 2620; https://doi.org/10.3390/cancers12092620 - 14 Sep 2020

Cited by 23 | Viewed by 3296

Abstract

With the introduction of immune checkpoint inhibitors (ICIs) and next-generation vascular endothelial growth factor receptor–tyrosine kinase inhibitors (VEGFR–TKIs), the survival of patients with advanced renal cell carcinoma (RCC) has improved remarkably. However, not all patients have benefited from treatments, and to date, there [...] Read more.

With the introduction of immune checkpoint inhibitors (ICIs) and next-generation vascular endothelial growth factor receptor–tyrosine kinase inhibitors (VEGFR–TKIs), the survival of patients with advanced renal cell carcinoma (RCC) has improved remarkably. However, not all patients have benefited from treatments, and to date, there are still no validated biomarkers that can be included in the therapeutic algorithm. Thus, the identification of predictive biomarkers is necessary to increase the number of responsive patients and to understand the underlying immunity. The clinical outcome of RCC patients is, in fact, associated with immune response. In this exploratory pilot study, we assessed the immune effect of TKI therapy in order to evaluate the immune status of metastatic renal cell carcinoma (mRCC) patients so that we could define a combination of immunological biomarkers relevant to improving patient outcomes. We profiled the circulating levels in 20 mRCC patients of exhausted/activated/regulatory T cell subsets through flow cytometry and of 14 immune checkpoint-related proteins and 20 inflammation cytokines/chemokines using multiplex Luminex assay, both at baseline and during TKI therapy. We identified the CD3⁺CD8⁺CD137⁺ and CD3⁺CD137⁺PD1⁺ T cell populations, as well as seven soluble immune molecules (i.e., IFNγ, sPDL2, sHVEM, sPD1, sGITR, sPDL1, and sCTLA4) associated with the clinical responses of mRCC patients, either modulated by TKI therapy or not. These results suggest an immunological profile of mRCC patients, which will help to improve clinical decision-making for RCC patients in terms of the best combination of strategies, as well as the optimal timing and therapeutic sequence. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Figure 1

13 pages, 3249 KiB

Open AccessArticle

Comparative Efficacy of First-Line Immune-Based Combination Therapies in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis

by Reza Elaidi, Letuan Phan, Delphine Borchiellini, Philippe Barthelemy, Alain Ravaud, Stéphane Oudard and Yann Vano

Cancers 2020, 12(6), 1673; https://doi.org/10.3390/cancers12061673 - 24 Jun 2020

Cited by 16 | Viewed by 3818

Abstract

Three drug combinations, ipilimumab-nivolumab (Ipi-Nivo), pembrolizumab-axitinib (Pembro-Axi), and avelumab-axitinib (Ave-Axi), have received regulatory approval in the USA and Europe for the treatment of metastatic renal cell carcinoma with clear cell component (mRCC). However, no head-to-head comparison data are available to identify the best [...] Read more.

Three drug combinations, ipilimumab-nivolumab (Ipi-Nivo), pembrolizumab-axitinib (Pembro-Axi), and avelumab-axitinib (Ave-Axi), have received regulatory approval in the USA and Europe for the treatment of metastatic renal cell carcinoma with clear cell component (mRCC). However, no head-to-head comparison data are available to identify the best option. Therefore, we aimed to compare these new treatments in a first-line setting. We conducted a systematic search in PubMed, the Cochrane Library, and clinicaltrials.gov for any randomized controlled trials of treatment-naïve patients with mRCC, from January 2015 to October 2019. The process was performed according to PRISMA guidelines. We performed a Bayesian network meta-analysis with two different approaches, a contrast-based model comparing HRs and ORs between studies and arm-based using parametric modeling. The outcomes for the analysis were overall survival, progression-free survival (PFS), and objective response rate. Our search identified 3 published phase 3 randomized clinical trials (2835 patients). In the contrast-based model, Ave-Axi (SUCRA = 83%) and Pembro-Axi (SUCRA = 80%) exhibited the best ranking probabilities for PFS. For overall survival (OS), Pembro-Axi (SUCRA = 96%) was the most preferable option against Ave-Axi and Ipi-Nivo. Objective response rate analysis showed Ave-Axi as the best (SUCRA: 94%) and Pembro-Axi as the second best option. In the parametric models, the risk of progression was comparable for Ave-Axi and Ipi-Nivo, whereas Pembro-Axi exhibited a lower risk during the first 6 months of treatment and a higher risk afterwards. Furthermore, Pembro-Axi exhibited a net advantage in terms of OS over the two other regimens, while Ave-Axi was the least preferable option. Overall evidence suggests that pembrolizumab plus axitinib seems to have a slight advantage over the other two combinations. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Figure 1

20 pages, 3321 KiB

Open AccessArticle

Cysteine Cathepsins Inhibition Affects Their Expression and Human Renal Cancer Cell Phenotype

by Magdalena Rudzińska, Alessandro Parodi, Valentina D. Maslova, Yuri M. Efremov, Neonila V. Gorokhovets, Vladimir A. Makarov, Vasily A. Popkov, Andrey V. Golovin, Evgeni Y. Zernii and Andrey A. Zamyatnin, Jr.

Cancers 2020, 12(5), 1310; https://doi.org/10.3390/cancers12051310 - 21 May 2020

Cited by 19 | Viewed by 3876

Abstract

Renal cancer would greatly benefit from new therapeutic strategies since, in advanced stages, it is refractory to classical chemotherapeutic approaches. In this context, lysosomal protease cysteine cathepsins may represent new pharmacological targets. In renal cancer, they are characterized by a higher expression, and [...] Read more.

Renal cancer would greatly benefit from new therapeutic strategies since, in advanced stages, it is refractory to classical chemotherapeutic approaches. In this context, lysosomal protease cysteine cathepsins may represent new pharmacological targets. In renal cancer, they are characterized by a higher expression, and they were shown to play a role in its aggressiveness and spreading. Traditional studies in the field were focused on understanding the therapeutic potentialities of cysteine cathepsin inhibition, while the direct impact of such therapeutics on the expression of these enzymes was often overlooked. In this work, we engineered two fluoromethyl ketone-based peptides with inhibitory activity against cathepsins to evaluate their potential anticancer activity and impact on the lysosomal compartment in human renal cancer. Molecular modeling and biochemical assays confirmed the inhibitory properties of the peptides against cysteine cathepsin B and L. Different cell biology experiments demonstrated that the peptides could affect renal cancer cell migration and organization in colonies and spheroids, while increasing their adhesion to biological substrates. Finally, these peptide inhibitors modulated the expression of LAMP1, enhanced the expression of E-cadherin, and altered cathepsin expression. In conclusion, the inhibition of cysteine cathepsins by the peptides was beneficial in terms of cancer aggressiveness; however, they could affect the overall expression of these proteases. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Graphical abstract

Review

Jump to: Research

13 pages, 696 KiB

Open AccessEditor’s ChoiceReview

New Therapeutic Interventions for Kidney Carcinoma: Looking to the Future

by Lucio Dell’Atti, Nicoletta Bianchi and Gianluca Aguiari

Cancers 2022, 14(15), 3616; https://doi.org/10.3390/cancers14153616 - 25 Jul 2022

Cited by 27 | Viewed by 5498

Abstract

Patients suffering from metastatic renal cell carcinoma (mRCC) show an overall survival rate of lower than 10% after 5 years from diagnosis. Currently, the first-line treatment for mRCC patients is based on antiangiogenic drugs that are able to inhibit tyrosine kinase receptors (TKI) [...] Read more.

Patients suffering from metastatic renal cell carcinoma (mRCC) show an overall survival rate of lower than 10% after 5 years from diagnosis. Currently, the first-line treatment for mRCC patients is based on antiangiogenic drugs that are able to inhibit tyrosine kinase receptors (TKI) in combination with immuno-oncology (IO) therapy or IO-IO treatments. Second-line therapy involves the use of other TKIs, immunotherapeutic drugs, and mTOR inhibitors. Nevertheless, many patients treated with mTOR and TK inhibitors acquire drug resistance, making the therapy ineffective. Therefore, the research of new therapeutic targets is crucial for improving the overall survival and quality of life of mRCC patients. The investigation of the molecular basis of RCC, especially in clear cell renal cell carcinoma (ccRCC), has led to the identification of different signaling pathways that are involved in renal carcinogenesis. Most of ccRCCs are associated with mutation in VHL gene, which mediates the degradation of hypoxia-inducible factors (HIFs), that, in turn, regulate the pathways related to tumorigenesis, including angiogenesis and invasion. Renal tumorigenesis is also associated with the activation of tyrosine kinases that modulate the PI3K-Akt-mTOR pathway, promoting cell proliferation and survival. In ccRCC, the abnormal activity of mTOR activates the MDM2 protein, which leads to the degradation of tumor suppressor p53 via proteasome machinery. In addition, p53 may be degraded by autophagy in a mechanism involving the enzyme transglutaminase 2 (TG2). Suppression of wild-type p53 promotes cell growth, invasion, and drug resistance. Finally, the activation of ferroptosis appears to inhibit cancer progression in RCC. In conclusion, these pathways might represent new therapeutic targets for mRCC. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Figure 1

22 pages, 1946 KiB

Open AccessReview

Tumor Microenvironment Features as Predictive Biomarkers of Response to Immune Checkpoint Inhibitors (ICI) in Metastatic Clear Cell Renal Cell Carcinoma (mccRCC)

by Audrey Simonaggio, Nicolas Epaillard, Cédric Pobel, Marco Moreira, Stéphane Oudard and Yann-Alexandre Vano

Cancers 2021, 13(2), 231; https://doi.org/10.3390/cancers13020231 - 10 Jan 2021

Cited by 51 | Viewed by 6601

Abstract

Renal cell carcinoma (RCC) is the seventh most frequently diagnosed malignancy with an increasing incidence in developed countries. Despite a greater understanding of the cancer biology, which has led to an increase of therapeutic options, metastatic clear cell renal cell carcinoma (mccRCC) still [...] Read more.

Renal cell carcinoma (RCC) is the seventh most frequently diagnosed malignancy with an increasing incidence in developed countries. Despite a greater understanding of the cancer biology, which has led to an increase of therapeutic options, metastatic clear cell renal cell carcinoma (mccRCC) still have a poor prognosis with a median five-years survival rate lower than 10%. The standard of care for mccRCC has changed dramatically over the past decades with the emergence of new treatments: anti-VEGFR tyrosine kinase inhibitors, mTOR Inhibitors and immune checkpoint inhibitors (ICI) such as anti-Programmed cell-Death 1 (PD-1) and anti-anti-Programmed Death Ligand-1 (PD-L1) used as monotherapy or as a combination with anti CTLA-4 or anti angiogenic therapies. In the face of these rising therapeutic options, the question of the therapeutic sequences is crucial. Predictive biomarkers are urgently required to provide a personalized treatment for each patient. Disappointingly, the usual ICI biomarkers, PD-L1 expression and Tumor Mutational Burden, approved in melanoma or non-small cell lung cancer (NSCLC) have failed to distinguish good and poor mccRCC responders to ICI. The tumor microenvironment is known to be involved in ICI response. Innovative technologies can be used to explore the immune contexture of tumors and to find predictive and prognostic biomarkers. Recent comprehensive molecular characterization of RCC has led to the development of robust genomic signatures, which could be used as predictive biomarkers. This review will provide an overview of the components of the RCC tumor microenvironment and discuss their role in disease progression and resistance to ICI. We will then highlight the current and future ICI predictive biomarkers assessed in mccRCC with a major focus on immunohistochemistry markers and genomic signatures. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Figure 1

24 pages, 585 KiB

Open AccessReview

Individualizing Systemic Therapies in First Line Treatment and beyond for Advanced Renal Cell Carcinoma

by Yasir Khan, Timothy D. Slattery and Lisa M. Pickering

Cancers 2020, 12(12), 3750; https://doi.org/10.3390/cancers12123750 - 13 Dec 2020

Cited by 13 | Viewed by 3891

Abstract

Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium [...] Read more.

Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium (IMDC) risk stratification. However, immune checkpoint inhibitors (ICI) have recently changed the treatment paradigm for advanced RCC particularly as the first-line systemic treatment modality. The combination of Ipilimumab and Nivolumab provides better disease control and long-term outcomes compared with the anti-VEGFr TKI Sunitinib for IMDC intermediate- to poor-risk patients and we now have the option of using ICI with TKI upfront for all IMDC risk groups. This poses a challenge for physicians, both to select the most suitable first line regimen and the most suitable subsequent therapy given the lack of data about sequencing in this setting. This treatment landscape is expected to become more complex with the emerging treatment options. Moreover, these therapeutic options cannot be generalized as significant variability exists between individual’s disease biologies and their physiologies for handling treatment adverse effects. Notable efforts are being made to identify promising predictive biomarkers ranging from neo-antigen load to gene expression profiling. These biomarkers need prospective validation to justify their utility in clinical practice and in treatment decision making. This review article discusses various clinicopathological characteristics that should be carefully evaluated to help select appropriate treatment and discusses the current status of biomarker-based selection. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Figure 1

25 pages, 462 KiB

Open AccessReview

Clinical and Pathological Characteristics of Metastatic Renal Cell Carcinoma Patients Needing a Second-Line Therapy: A Systematic Review

by Nicola Longo, Marco Capece, Giuseppe Celentano, Roberto La Rocca, Gianluigi Califano, Claudia Collà Ruvolo, Carlo Buonerba, Fabio Esposito, Luigi Napolitano, Francesco Mangiapia, Ferdinando Fusco, Vincenzo Mirone and Massimiliano Creta

Cancers 2020, 12(12), 3634; https://doi.org/10.3390/cancers12123634 - 4 Dec 2020

Cited by 10 | Viewed by 2514

Abstract

A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included [...] Read more.

A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included papers that met the following criteria: original research; English language; human studies; enrolling mRCC patients entering a second-line therapy. Twenty-nine studies enrolling 7650 patients (73.5% male, mean age: 55 to 70 years) were included. Clear cell histology was reported in 74.4% to 100% of cases. Tyrosine kinase inhibitors, immunotherapy, bevacizumab, mTOR inhibitors, and chemotherapy were adopted as first line option in 68.5%, 29.2%, 2.9%, 0.6%, and 0.2% of patients, respectively. Discontinuation of first-line therapy was due to progression and toxicity in 18.4% to 100% and in 17% to 48.8% of patients, respectively. Eastern Cooperative Oncology Group performance status score was 0 or 1 in most cases. Most prevalent prognostic categories according to the International Metastatic RCC Database Consortium and Memorial Sloan–Kettering Cancer Centre score were intermediate and good. About 77.8% of patients harboured ≥2 metastatic sites. In conclusion, patients who enter a second-line therapy are heterogeneous in terms of a clinical-pathological profile. Tailoring of second-line treatment strategies is strongly advocated. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Graphical abstract

13 pages, 643 KiB

Open AccessReview

Targeting the Deterministic Evolutionary Trajectories of Clear Cell Renal Cell Carcinoma

by Adam Kowalewski, Marek Zdrenka, Dariusz Grzanka and Łukasz Szylberg

Cancers 2020, 12(11), 3300; https://doi.org/10.3390/cancers12113300 - 9 Nov 2020

Cited by 7 | Viewed by 3060

Abstract

The emergence of clinical resistance to currently available systemic therapies forces us to rethink our approach to clear cell renal cell carcinoma (ccRCC). The ability to influence ccRCC evolution by inhibiting processes that propel it or manipulating its course may be an adequate [...] Read more.

The emergence of clinical resistance to currently available systemic therapies forces us to rethink our approach to clear cell renal cell carcinoma (ccRCC). The ability to influence ccRCC evolution by inhibiting processes that propel it or manipulating its course may be an adequate strategy. There are seven deterministic evolutionary trajectories of ccRCC, which correlate with clinical phenotypes. We suspect that each trajectory has its own unique weaknesses that could be exploited. In this review, we have summarized recent advances in the treatment of ccRCC and demonstrated how to improve systemic therapies from the evolutionary perspective. Since there are only a few evolutionary trajectories in ccRCC, it appears feasible to use them as potential biomarkers for guiding intervention and surveillance. We believe that the presented patient stratification could help predict future steps of malignant progression, thereby informing optimal and personalized clinical decisions. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Figure 1

20 pages, 332 KiB

Open AccessReview

Predicting Response to Immunotherapy in Metastatic Renal Cell Carcinoma

by Matthew D. Tucker and Brian I. Rini

Cancers 2020, 12(9), 2662; https://doi.org/10.3390/cancers12092662 - 18 Sep 2020

Cited by 32 | Viewed by 8000

Abstract

Immunotherapy-based combinations, driven by PD-1, PD-L1, and CTLA-4 inhibitors, has altered the treatment landscape for metastatic renal cell carcinoma (RCC). Despite significant improvements in clinical outcomes, many patients do not experience deep or lasting benefits. Recent efforts to determine which patients are most [...] Read more.

Immunotherapy-based combinations, driven by PD-1, PD-L1, and CTLA-4 inhibitors, has altered the treatment landscape for metastatic renal cell carcinoma (RCC). Despite significant improvements in clinical outcomes, many patients do not experience deep or lasting benefits. Recent efforts to determine which patients are most likely to benefit from immunotherapy and immunotherapy-based combinations have shown promise but have not yet affected clinical practice. PD-L1 expression via immunohistochemistry (IHC) has shown promise in a few clinical trials, although variations in the IHC assays as well as the use of different values for positivity presents unique challenges for this potential biomarker. Several other candidate biomarkers were investigated including tumor mutational burden, gene expression signatures, single gene mutations, human endogenous retroviruses, the gastrointestinal microbiome, and peripheral blood laboratory markers. While individually these biomarkers have yet to explain the heterogeneity of treatment response to immunotherapy, using aggregate information from these biomarkers may inform clinically useful predictive biomarkers. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Graphical abstract

16 pages, 1121 KiB

Open AccessReview

The Value of PD-L1 Expression as Predictive Biomarker in Metastatic Renal Cell Carcinoma Patients: A Meta-Analysis of Randomized Clinical Trials

by Alberto Carretero-González, David Lora, Isabel Martín Sobrino, Irene Sáez Sanz, María T. Bourlon, Urbano Anido Herranz, Nieves Martínez Chanzá, Daniel Castellano and Guillermo de Velasco

Cancers 2020, 12(7), 1945; https://doi.org/10.3390/cancers12071945 - 17 Jul 2020

Cited by 60 | Viewed by 3735

Abstract

Immune checkpoint inhibitors (ICIs) are soluble antibodies that have dramatically changed the outcomes including overall survival in a subset of kidney tumors, specifically in renal cell carcinoma (RCC). To date, there is no a single predictive biomarker approved to be used to select [...] Read more.

Immune checkpoint inhibitors (ICIs) are soluble antibodies that have dramatically changed the outcomes including overall survival in a subset of kidney tumors, specifically in renal cell carcinoma (RCC). To date, there is no a single predictive biomarker approved to be used to select the patients that achieve benefit from ICIs targeting. It seems reasonable to analyze whether the programmed death-ligand 1 (PD-L1) expression could be useful. To assess the role of PD-L1 expression as a potential predictive biomarker for benefit of ICIs in RCC patients, we performed a search of randomized clinical trials (RCTs) comparing ICIs (monotherapy or in combination with other therapies) to standard of care in metastatic RCC patients according to PRISMA guidelines. Trials must have included subgroup analyses evaluating the selected outcomes (progression-free survival (PFS) and overall survival (OS)) in different subsets of patients according to PD-L1 expression on tumor samples. Hazard ratios with confidence intervals were used as the measure of efficacy between groups. A total of 4635 patients (six studies) were included (ICIs arm: 2367 patients; standard of care arm: 2268 patients). Globally, PFS and OS results favored ICIs. Differential expression of PD-L1 on tumor samples could select a subset of patients who could benefit more in terms of PFS (those with higher levels; p-value for difference between subgroups: <0.0001) but it did not seem to impact in OS results (p-value for difference: 0.63). As different methods to assess PD-L1 positivity were used among trials, this heterogeneity could have an influence on the results. PD-L1 could represent a biomarker to test PFS in clinical trials but its value for OS is less clear. In this meta-analysis, the usefulness of PD-L1 expression as a predictive biomarker to select treatment in metastatic RCC patients was not clearly shown. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Figure 1

16 pages, 1646 KiB

Open AccessReview

Therapeutic Targeting of Autophagy for Renal Cell Carcinoma Therapy

by Trace M. Jones, Jennifer S. Carew and Steffan T. Nawrocki

Cancers 2020, 12(5), 1185; https://doi.org/10.3390/cancers12051185 - 7 May 2020

Cited by 32 | Viewed by 4817

Abstract

Kidney cancer is the 7th most prevalent form of cancer in the United States with the vast majority of cases being classified as renal cell carcinoma (RCC). Multiple targeted therapies have been developed to treat RCC, but efficacy and resistance remain a challenge. [...] Read more.

Kidney cancer is the 7th most prevalent form of cancer in the United States with the vast majority of cases being classified as renal cell carcinoma (RCC). Multiple targeted therapies have been developed to treat RCC, but efficacy and resistance remain a challenge. In recent years, the modulation of autophagy has been shown to augment the cytotoxicity of approved RCC therapeutics and overcome drug resistance. Inhibition of autophagy blocks a key nutrient recycling process that cancer cells utilize for cell survival following periods of stress including chemotherapeutic treatment. Classic autophagy inhibitors such as chloroquine and hydroxychloroquine have been introduced into phase I/II clinical trials, while more experimental compounds are moving forward in preclinical development. Here we examine the current state and future directions of targeting autophagy to improve the efficacy of RCC therapeutics. Full article

(This article belongs to the Special Issue Advances in the Treatment of Renal Cell Carcinoma)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Advances in the Treatment of Renal Cell Carcinoma

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (12 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI