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Cancers
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Biomarkers in Renal Cell Carcinoma Treated with TKI or IO
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Biomarkers in Renal Cell Carcinoma Treated with TKI or IO

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 10099

Special Issue Editor

Prof. Dr. Stéphane Oudard

E-Mail Website
Guest Editor
Medical Oncology Department, Georges Pompidou Hospital, University of Paris, 75006 Paris, France
Interests: urinary cancers (kidney, prostate and bladder); immunotherapy; targeted therapy

Special Issue Information

Dear Colleagues

The standard of care for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically in the past few years with the emergence of immune checkpoint inhibitors (ICI): anti-PD(L)-1 used as a monotherapy or in combination either with an anti-CTLA-4 or with an anti-angiogenic molecule (VEGFR tyrosine kinase inhibitor (TKI)). These combinations are now recommended in first-line setting for mccRCC, according to the last European recommendations (ESMO 2021). In the face of these new therapeutic options, the question of selecting the best treatment arises, as well as the optimal sequence. Predictive biomarkers are required to guide the therapeutic choice and 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 mRCC has led to the development of robust genomic signatures, which could be used as predictive biomarkers.

This Special Issue will cover all aspects of exploring novel and strategic approaches for the treatment of renal cell carcinoma, involving original research and comprehensive reviews including but not limited to investigational therapies with immunotherapy and antiangiogenic drugs in a preclinical or clinical setting (combined with conventional therapies or as a monotherapy), molecular mechanisms of treatment response or design strategies, and the use of robust prognostic or predictive biomarkers. We aim to provide an update on the current status and the future directions of this exciting field of research that is aiming to improve renal cell carcinoma patient outcome.

Prof. Dr. Stéphane Oudard
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • renal cell carcinoma
  • tyrosine kinase inhibitors
  • checkpoint inhibitors
  • immunotherapy
  • treatment resistance
  • targeted therapy
  • precision medicine
  • biomarkers

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Published Papers (4 papers)

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Research

13 pages, 904 KiB  
Article
The Efficacy and Safety of Immune Checkpoint Inhibitor and Tyrosine Kinase Inhibitor Combination Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Real-World Cohort Study
by Koji Iinuma, Toyohiro Yamada, Koji Kameyama, Tomoki Taniguchi, Kei Kawada, Takashi Ishida, Shingo Nagai, Torai Enomoto, Shota Ueda, Kimiaki Takagi, Makoto Kawase, Shinichi Takeuchi, Kota Kawase, Daiki Kato, Manabu Takai, Keita Nakane and Takuya Koie
Cancers 2023, 15(3), 947; https://doi.org/10.3390/cancers15030947 - 2 Feb 2023
Cited by 7 | Viewed by 2217
Abstract
We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We enrolled 51 patients to receive ICI+TKI therapy for [...] Read more.
We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We enrolled 51 patients to receive ICI+TKI therapy for mRCC at 9 Japanese institutions. The overall survival (OS) of the patients treated with ICI+TKI was the primary endpoint., and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Furthermore, we analyzed the clinical prognostic and predictive factors in patients with mRCC treated with ICI+TKI therapy. Seven months was the median follow-up period. The OS rates at 6, 12, and 18 months were 93.1, 82.5, and 68.8%, respectively. The median PFS for patients who received ICI+TKI was 19.0 months, ORR was 68.6%, and DCR was 88.2%. ICI+TKI-related adverse events occurred in 43 patients (84.3%) with any grade and in 22 patients (43.1%) with grade ≥3. Treatment selection with poor prognostic factors may be prudent, even though ICI+TKI is an efficacious and safe first-line treatment in patients with mRCC. Full article
(This article belongs to the Special Issue Biomarkers in Renal Cell Carcinoma Treated with TKI or IO)
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21 pages, 42156 KiB  
Article
The Inflammasomes Adaptor Protein PYCARD Is a Potential Pyroptosis Biomarker Related to Immune Response and Prognosis in Clear Cell Renal Cell Carcinoma
by Jia-Qi Su, Xi Tian, Wen-Hao Xu, Aihetaimujiang Anwaier, Shi-Qi Ye, Shu-Xuan Zhu, Yue Wang, Jun Gu, Guo-Hai Shi, Yuan-Yuan Qu, Hai-Liang Zhang and Ding-Wei Ye
Cancers 2022, 14(20), 4992; https://doi.org/10.3390/cancers14204992 - 12 Oct 2022
Cited by 5 | Viewed by 2966
Abstract
PYCARD is a protein engaged in inflammation, pyroptosis, and apoptosis. However, the function of PYCARD in human cancers remains unclear. The objective of our study was to explore PYCARD expression and prognostic value in human cancers. Public databases were used to assess PYCARD [...] Read more.
PYCARD is a protein engaged in inflammation, pyroptosis, and apoptosis. However, the function of PYCARD in human cancers remains unclear. The objective of our study was to explore PYCARD expression and prognostic value in human cancers. Public databases were used to assess PYCARD expression and prognostic value. The TISIDB database was used to explore the associations between PYCARD expression and different immune subtypes. The correlations between PYCARD expression and ICP genes, MMR genes, MSI, and TMB were also investigated. The immunotherapy response was assessed using the TIDE database. Single-cell RNA databases evaluated the PYCARD expression of immune cells. External datasets and immunohistochemical staining were conducted to validate PYCARD expression and prognostic value. The results showed that PYCARD expression varied in several cancers and was associated with prognosis, immune-related genes, published biomarkers, and immunotherapy response. Of note, PYCARD expression was upregulated in renal cancers with high diagnostic ability. Upregulation of PYCARD was correlated with worse prognosis in KIRC and external validation cohorts. In conclusion, PYCARD demonstrated strong correlations with prognosis, immune response, and disease progression in pan-cancer analysis. In ccRCC, PYCARD might serve as a biomarker for diagnosis and therapeutic target-boosting immunotherapy response. Full article
(This article belongs to the Special Issue Biomarkers in Renal Cell Carcinoma Treated with TKI or IO)
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12 pages, 342 KiB  
Article
Role of the Systemic Immune-Inflammation Index in Patients with Metastatic Renal Cell Carcinoma Treated with First-Line Ipilimumab plus Nivolumab
by Viktoria Stühler, Lisa Herrmann, Steffen Rausch, Arnulf Stenzl and Jens Bedke
Cancers 2022, 14(12), 2972; https://doi.org/10.3390/cancers14122972 - 16 Jun 2022
Cited by 12 | Viewed by 1862
Abstract
Background: The aim of this study was to evaluate the predictive and prognostic value of the systemic immune-inflammation index (SII) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab plus nivolumab. Methods: This retrospective study included forty-nine mRCC patients treated [...] Read more.
Background: The aim of this study was to evaluate the predictive and prognostic value of the systemic immune-inflammation index (SII) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab plus nivolumab. Methods: This retrospective study included forty-nine mRCC patients treated with first-line ipilimumab plus nivolumab at the Department of Urology of the University of Tuebingen, Germany. SII was assessed before starting ipilimumab plus nivolumab therapy at the time of first imaging and at tumor progression. Optimal SII cut-off was stratified by ROC-analysis. Univariable and multivariable Cox regression analyses were used to evaluate the predictive and prognostic value of SII. Results: Optimal SII cut-off was 788. Twenty-nine/forty-nine patients had high SII (≥788) before initiation of ipilimumab plus nivolumab. High SII was an independent prognostic factor for worse progression-free (HR 2.70, p = 0.014) and overall survival (HR 10.53, p = 0.025). The clinical benefit rate was higher for patients with low SII if compared to high SII (80% vs. 32.1%). An increase in SII > 20% from baseline after twelve weeks of therapy was associated with progression at first imaging (p = 0.003). Conclusions: SII is both prognostic and predictive and could refine decision making in patients with unclear imaging on therapy with ipilimumab plus nivolumab. Full article
(This article belongs to the Special Issue Biomarkers in Renal Cell Carcinoma Treated with TKI or IO)
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10 pages, 511 KiB  
Article
Metastatic Renal Medullary and Collecting Duct Carcinoma in the Era of Antiangiogenic and Immune Checkpoint Inhibitors: A Multicentric Retrospective Study
by Zoé Guillaume, Emeline Colomba, Jonathan Thouvenin, Carolina Saldana, Luca Campedel, Clément Dumont, Brigitte Laguerre, Denis Maillet, Cécile Vicier, Frédéric Rolland, Delphine Borchiellini, Philippe Barthelemy, Laurence Albiges, Edouard Auclin, Matthieu Roulleaux Dugage, Stéphane Oudard and Constance Thibault
Cancers 2022, 14(7), 1678; https://doi.org/10.3390/cancers14071678 - 25 Mar 2022
Cited by 9 | Viewed by 2404
Abstract
Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are two rare subtypes of kidney cancer with a poor prognosis in the metastatic setting. Beyond first-line treatment, there are no standard-of-care therapies. This retrospective study assessed the efficacy of treatments after first-line chemotherapy [...] Read more.
Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are two rare subtypes of kidney cancer with a poor prognosis in the metastatic setting. Beyond first-line treatment, there are no standard-of-care therapies. This retrospective study assessed the efficacy of treatments after first-line chemotherapy in 57 patients with metastatic (m) CDC (n = 35) or RMC (n = 22) treated between 2010 and 2019 at 11 French centers. The median age was 53 years; overall, 60% (n = 34) of patients were metastatic at diagnosis. After a median follow-up of 13 months, the median overall survival was 12 (95% CI, 11–16) months. All patients received first-line platinum chemotherapy ± bevacizumab, with a median time to progression of 7.27 (95% CI, 7–100 months and an objective response rate (ORR) of 39% (95% CI, 26–52%). Patients received a median of two (1–5) treatment lines. Subsequent treatments included tyrosine kinase inhibitors (n = 12), chemotherapy (n = 34), and checkpoint inhibitors (n = 20), with ORR ranging 10–15% and disease control rates ranging 24–50%. The duration of response for all treatments was ~2 months. Notably, nine patients with CDC were still alive > two years after metastatic diagnosis. Beyond first-line therapy, treatments showed very low antitumor activity in mCDC/RMC. A better understanding of the biology of those rare tumors is urgently needed in order to identify potential targets. Full article
(This article belongs to the Special Issue Biomarkers in Renal Cell Carcinoma Treated with TKI or IO)
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