-
American Society of Clinical Oncology... Jan 2024Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and...
Immune checkpoint inhibitors have significantly transformed the treatment paradigm for metastatic renal cell carcinoma (RCC), offering prolonged overall survival and achieving remarkable deep and durable responses. However, given the multiple ICI-containing, standard-of-care regimens approved for RCC, identifying biomarkers that predict therapeutic response and resistance is of critical importance. Although tumor-intrinsic features such as pathological characteristics, genomic alterations, and transcriptional signatures have been extensively investigated, they have yet to provide definitive, robust predictive biomarkers. Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Biomarkers; Biomedical Research; Gene Expression Profiling
PubMed: 38207251
DOI: 10.1200/EDBK_430734 -
The FEBS Journal Sep 2022Renal carcinoma is a common malignancy for which the underlying molecular mechanisms warrant further investigation. T cell activation inhibitor mitochondrial (TCAIM), a...
Renal carcinoma is a common malignancy for which the underlying molecular mechanisms warrant further investigation. T cell activation inhibitor mitochondrial (TCAIM), a mitochondrial protein, was found to be expressed to a low extent in renal carcinoma specimens. However, its role in carcinomas remains unclear. In the present study, the role of TCAIM in renal carcinoma was explored through loss-of-function and gain-of-function experiments. Here, we showed that TCAIM delayed the growth of renal carcinoma cells both in vitro and in vivo by modulating their cell cycle progress. Additionally, TCAIM also enhanced their sensitivity to sunitinib by aggravating apoptosis. Furthermore, TCAIM also decreased the adhesion and migration of renal carcinoma cells. Moreover, the transcription of TCAIM was regulated by vitamin D receptor, which acts as a transcriptional factor. To identify the pathways regulated by TCAIM, 425 unique proteins bound to TCAIM were pulled down through co-immunoprecipitation and analyzed by mass spectrometry followed by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis. In summary, the present study reveals a tumor-suppressor role of TCAIM in renal carcinoma cells, as well as its upstream regulation and downstream potential mechanisms. Our study provides theoretical bases and novel insights with respect to the development of new therapeutic strategies for the treatment of renal carcinoma.
Topics: Carcinoma, Renal Cell; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Lymphocyte Activation; Mitochondrial Proteins; Sunitinib
PubMed: 35238167
DOI: 10.1111/febs.16417 -
Postepy Biochemii Jun 2019Cancers account for 85% of renal tumors. In Poland renal cancer is diagnosed in almost four thousands patients every year and two thousands of them dies. The most common... (Review)
Review
Cancers account for 85% of renal tumors. In Poland renal cancer is diagnosed in almost four thousands patients every year and two thousands of them dies. The most common subtype of renal cancer is clear cell renal cell carcinoma (ccRCC), which accounts for 80-90% of all renal cancer cases. ccRCC is resistant to chemo- and radiotherapy. More and more data suggest that tumor growth is a result of proliferation and differentiation of a small population of cells called cancer stem cells (CSC). CSCs are responsible for tumor progression and for the resistance to chemo- and radiotherapy. This publication covers the role the CSCs and their origin in renal cell carcinoma, with particular emphasis on clear cell subtype.
Topics: Carcinoma, Renal Cell; Cell Differentiation; Humans; Kidney Neoplasms; Neoplastic Stem Cells; Poland
PubMed: 31642647
DOI: 10.18388/pb.2019_250 -
Human Vaccines & Immunotherapeutics Dec 2023For years, prospective randomized clinical trials excluded patients with non-conventional histologies of renal cell carcinoma (RCC). The paucity of data has led to... (Review)
Review
For years, prospective randomized clinical trials excluded patients with non-conventional histologies of renal cell carcinoma (RCC). The paucity of data has led to adopting the same treatment strategies used for clear-cell RCC (ccRCC). In the present narrative review, we explored state of the art about use of immune checkpoint inhibitors (ICIs) in variant histologies of RCC. According to the results collected, ICIs as monotherapy showed promising antitumor activity in advanced non-clear cell (ncc)RCC. The objective response rate (ORR) was similar to that observed with single-agent anti-PD-1 in the ccRCC population, either in the first-line or the second-line setting, and responder patients experienced an early and durable benefit. Combined ICI-based strategies have shown increasing evidence in nccRCC and robust results in the sarcomatoid variants of RCC. A definitive recommendation about treating non-conventional histologies, either in adjuvant or metastatic settings, should be supported by more extensive dedicated trials.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Immune Checkpoint Inhibitors; Antineoplastic Agents; Prospective Studies
PubMed: 36758960
DOI: 10.1080/21645515.2023.2171672 -
International Journal of... 2021Tubulocystic renal cell carcinoma is a rare neoplasm of kidney with low metastatic tendency. There has only been a relatively small collection of literature dedicated to... (Review)
Review
Tubulocystic renal cell carcinoma is a rare neoplasm of kidney with low metastatic tendency. There has only been a relatively small collection of literature dedicated to this subtype. Here we present two cases diagnosed in our center with detailed clinical information. Along with literature review, we aim to paint a comprehensive profile of TC-RCC. Hematuria and asthenia could be the chief complaints although most patients are asymptomatic. This lesion has a signature multilocular cystic form on radiology and enhancement of septa should reveal malignancy. Histologically, the cysts are lined by a single layer of flattened, cuboidal/columnar, and hobnail epithelium with enlarged nuclei and intermediate to large nucleoli. PAX8 and AMACR are most commonly positive while CD10 or CK7 could be focally stained in some cases. Overall, the diagnosis of TC-RCC should be based on comprehensive clinical and molecular results because early determination of the lesion could prelude a timely intervention and favorable prognosis.
Topics: Aged; Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Male; Middle Aged
PubMed: 33726547
DOI: 10.1177/20587384211002966 -
International Journal of Molecular... Sep 2020Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known... (Review)
Review
Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known for interfering with hypoxia processes. Renal carcinoma encompasses a broad spectrum of histological entities and is also described as a heterogeneous malignant tumor. Recently, various combinations of checkpoint inhibitors and targeted therapies have been validated to manage this disease. Reliable markers to confirm the diagnosis, estimate the prognosis, predict or monitor the treatment response are required. Molecular imaging developments allow a comprehensive analysis of the tumor, overcoming the spatial heterogeneity issue. CAIX, being highly expressed at the tumor cell surfaces of clear cell renal carcinoma, also represents a potential treatment target. In this manuscript we reviewed the current knowledge from the literature on the pathophysiological interactions between renal cell carcinoma and CAIX, the role of CAIX as a marker for diagnosis, prognosis, treatment monitoring and molecular imaging, and the potential target for therapeutic strategies.
Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Carbonic Anhydrase IX; Carcinoma, Renal Cell; Cell Cycle Checkpoints; Disease Management; Gene Expression Regulation, Neoplastic; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypoxia; Kidney Neoplasms; Molecular Imaging; Molecular Targeted Therapy; Prognosis; Recombinant Fusion Proteins; Signal Transduction
PubMed: 32998233
DOI: 10.3390/ijms21197146 -
International Journal of Molecular... Nov 2019Obesity is a well-known risk factor for renal cell carcinoma (RCC) development. However, the RCC-obesity link has not been fully addressed when considering a... (Review)
Review
Obesity is a well-known risk factor for renal cell carcinoma (RCC) development. However, the RCC-obesity link has not been fully addressed when considering a comprehensive scenario starting from pathogenetic aspects through pathological issues up to the outcome of medical treatment. We therefore conducted an electronic PubMed search using keywords "obesity", "body mass index", "overweight", "renal cell carcinoma/kidney cancer", "medical treatment", "targeted therapy", and "immunotherapy/immune checkpoint inhibitors". The selected data supported a crosstalk between adipose tissue (adipocytes and other white adipose tissue cells) and cancer cells inducing several signaling pathways that finally stimulated angiogenesis, survival, and cellular proliferation. Accurate sampling of renal sinus fat correlated with a prognostic value. Retrospective clinical evidence in metastatic RCC patients with higher body mass index (BMI) and treated with targeted therapies and/or immune checkpoint inhibitors showed advantageous survival outcomes. Therefore, obesity may influence the course of RCC patients, although the interplay between obesity/BMI and RCC warrants a large prospective confirmation. We are therefore still far from determining a clear role of obesity as a prognostic/predictive factor in metastatic RCC patients undergoing targeted therapy and immunotherapy.
Topics: Animals; Carcinoma, Renal Cell; Humans; Immunotherapy; Kidney Neoplasms; Molecular Targeted Therapy; Obesity; Prognosis; Treatment Outcome
PubMed: 31766196
DOI: 10.3390/ijms20225683 -
Journal of Translational Medicine Feb 2023Cell-cell communications of various cell populations within tumor microenvironment play an essential role in primary tumor growth, metastasis evolution, and immune...
BACKGROUND
Cell-cell communications of various cell populations within tumor microenvironment play an essential role in primary tumor growth, metastasis evolution, and immune escape. Nevertheless, comprehensive investigation of cell-cell communications in the ccRCC (Clear cell renal carcinoma) microenvironment and how this interplay affects prognosis still remains limited.
METHODS
Intercellular communications were characterized by single-cell data. Firstly, we employed "CellChat" package to characterize intercellular communications across all types of cells in microenvironment in VHL mutated and non-mutated samples from 8 patients, respectively. And pseudotime trajectory analyses were performed with monocle analyses. Finally clinical prognosis and immunotherapy efficacy with different landscapes of intercellular interplay are evaluated by TCGA-KIRC and immunotherapy cohort.
RESULTS
Firstly, the VHL phenotype may be related to the intercellular communication landscape. And trajectory analysis reveals the potential relationship of cell-cell communication molecules with T cells and Myeloid cells differentiation. Furthermore, those molecules also correlate with the infiltration of T cells and Myeloid cells. A tumor cluster with highly expressed ligands was defined by quantitative analysis and transcription factor enrichment analysis, which was identified to be pivotal for intercellular communications in tumor microenvironment. Finally, bulk data indicates bulk that different clusters with different intercellular communications have significant predictive value for prognosis and distinguished immunotherapy efficiency.
CONCLUSIONS
The intercellular communication landscapes of VHL wild and VHL mutant ccRCC vary. Intercellular communications within the tumor microenvironment also influence T cell and myeloid cell development and infiltration, as well as predict clinical prognosis and immunotherapy efficacy in ccRCC.
Topics: Humans; Carcinoma, Renal Cell; Tumor Microenvironment; Cell Communication; Factor Analysis, Statistical; Kidney Neoplasms; Prognosis
PubMed: 36765369
DOI: 10.1186/s12967-022-03858-x -
Urologia Internationalis 2010Renal cell carcinoma (RCC) represents 3% of adult malignancies. About 30% of RCC patients develop metastatic disease. So far, drugs cannot significantly increase the... (Review)
Review
Renal cell carcinoma (RCC) represents 3% of adult malignancies. About 30% of RCC patients develop metastatic disease. So far, drugs cannot significantly increase the survival of these patients. We present a recent review of proteomics and RCC. Proteomic technologies have been used in the research to discover new markers of RCC that might increase survival. Furthermore, newly discovered markers cannot increase patient survival, rather their prognostic value supporting therapeutic decisions or new agents targeted at these new markers. More research is required to develop proteomic technologies and biomarkers for identification and validation.
Topics: Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Early Detection of Cancer; Humans; Kidney Neoplasms; Neoplasm Proteins; Precision Medicine; Predictive Value of Tests; Prognosis; Proteomics
PubMed: 20224258
DOI: 10.1159/000296283 -
Cancer Treatment Reviews Jun 2021Non-clear cell renal cell carcinomas (nccRCC) represent a highly heterogeneous group of kidney tumors, consisting of the following subtypes: papillary carcinomas,... (Review)
Review
Non-clear cell renal cell carcinomas (nccRCC) represent a highly heterogeneous group of kidney tumors, consisting of the following subtypes: papillary carcinomas, chromophobe renal cell carcinoma, so-called unclassified carcinomas or aggressive uncommon carcinomas such as Bellini carcinoma, renal cell carcinoma (RCC) with ALK rearrangement or fumarate hydratase-deficient RCC. Although non-clear cell cancers account for only 15 to 30% of renal tumors, they are often misclassified and accurate diagnosis continues to be an issue in clinical practice. Current therapeutic strategy of metastatic nccRCC is based primarily on guidelines established for clear cell tumors, the most common subtype, however this approach remains poorly defined. To date, published clinical trials for all histological nccRCC subtypes have been collectively characterized into one group, in contrast to clear cell RCC, and given the small numbers of cases, the interpretation of study results continues to be challenging. This review summarizes the available literature for each nccRCC subtype and highlights the lack of supportive evidence from prospective clinical trials and retrospective studies. Future trials should evaluate treatment approaches which focus on a specific histological subtype and progress in treating nccRCC will be contingent on understanding the unique biology of their individual histologies.
Topics: Antineoplastic Agents; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Practice Guidelines as Topic; Prognosis
PubMed: 34015728
DOI: 10.1016/j.ctrv.2021.102191