Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immune Checkpoint Inhibitor in First-Line Treatment of Metastatic Renal Cell Carcinoma: A Review of Current Evidence and Future Directions.

ABSTRACT: The incidence of renal cell carcinoma (RCC) is rising and metastatic RCC carries a very poor prognosis. The treatment paradigm for metastatic RCC has shifted dramatically in the last decade with multi-targeted tyrosine kinase inhibitors (TKI) previously used as first-line treatment but its utility is limited by short-lived efficacy and rapid disease progression. The dysregulation of immune cells in the tumour microenvironment contributes to unregulated growth of RCC. Thus, the use of immune checkpoint inhibitors has become first-line treatment for metastatic RCC and has offered dramatic improvement in clinical benefit and survival. Treatment with immune checkpoint inhibitor in combination with TKI appears to be promising in offering even greater response rates. The treatment for metastatic RCC continues to evolve and ongoing advances with new targeted agents and biomarkers are needed to continue to improve prognosis in the future.

SUBMITTER: Tung I

PROVIDER: S-EPMC8435744 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Immune Checkpoint Inhibitor Rechallenge in Renal Cell Carcinoma: Current Evidence and Future Directions.

Project description:Immune checkpoint inhibitor-based therapies represent the current standard of care in the first-line treatment of advanced renal cell carcinoma. Despite a clear benefit in survival outcomes, a considerable proportion of patients experience disease progression; prospective data about second-line therapy after first-line treatment with immune checkpoint inhibitors are limited to small phase II studies. As with other solid tumors (such as melanoma and non-small cell lung cancer), preliminary data about the clinical efficacy of rechallenge of immunotherapy (alone or in combination with other drugs) in renal cell carcinoma are beginning to emerge. Nevertheless, the role of rechallenge in immunotherapy in this setting of disease remains unclear and cannot be considered a standard of care; currently some randomized trials are exploring this approach in patients with metastatic renal cell carcinoma. The aim of our review is to summarize main evidence available in the literature concerning immunotherapy rechallenge in renal carcinoma, especially focusing on biological rationale of resistance to immune checkpoint inhibitors, on the published data of clinical efficacy and on future perspectives.

| S-EPMC10296725 | biostudies-literature

Optimal first-line and second-line treatments for metastatic renal cell carcinoma: current evidence.

Project description:Since 2005, an abundance of targeted agents has been approved for the treatment of metastatic renal cell carcinoma (mRCC), without any specification as to what may be the most optimal first-line and second-line sequence. Hence, our objective was to critically examine the evidence supporting the use of first-line and second-line agents in the management of mRCC. Our review suggests that in first line, sunitinib and pazopanib represent treatment options for patients with favorable or intermediate-risk features and clear cell histology. Unfortunately, the Phase III trial cannot conclusively prove the noninferiority of pazopanib relative to sunitinib. Hence, the use of sunitinib as first-line standard of care remains justified. Pazopanib represents an option for specific patients in whom sunitinib might not be tolerated. In patients with poor-risk features, temsirolimus represents the only option supported with level 1 evidence. Less optimal alternatives include sunitinib and bevacizumab combined with interferon, based on the minimal inclusion of poor-risk patients in pivotal Phase III studies of these two molecules. In patients with non-clear cell mRCC, the use of temsirolimus is supported by Phase III data, unlike for any other molecule. In second line, the options consist of everolimus and axitinib. However, the axitinib data are substantially more robust given the inclusion of more patients considered as true second-line, and validly justify the choice of axitinib over everolimus. Nonetheless, the Phase III trial of everolimus may be considered as level 1 evidence for use as third-line or subsequent lines of therapy.

| S-EPMC4219683 | biostudies-literature

Checkpoint inhibitors for renal cell carcinoma: current landscape and future directions.

Project description:Immunotherapy with checkpoint inhibitors has arrived and begun to change the landscape of clinical oncology, including for patients with renal cell carcinoma. Specifically, drugs targeting the programmed death 1 and cytotoxic T-lymphocyte associated antigen pathways have demonstrated remarkable responses for patients in clinical trials. In this article, we review the most recent available data for immune checkpoint inhibitors for patients with renal cell carcinoma. We discuss potential strategies for rational combination therapies in these patients, some of which are currently being studied, and address important future considerations for use of these novel agents in the years to come.

| S-EPMC8819587 | biostudies-literature

Front-Line Therapy for Metastatic Renal Cell Carcinoma: A Perspective on the Current Algorithm and Future Directions.

Project description:Over the last decade, the treatment paradigm of metastatic renal cell carcinoma has rapidly evolved, with notable changes in the front-line setting. Combination therapies involving the use of either doublet therapy with immune checkpoint inhibitors or combination VEGFR-directed therapies with immune checkpoint inhibitors have significantly improved clinical outcomes, including prolonged overall survival and durable response to treatment. We aim to highlight the Food and Drug Administration-approved front-line therapy options, the navigation of treatment selection, and the future directions of metastatic renal cell carcinoma therapies.

| S-EPMC9106028 | biostudies-literature

Targeted therapy for metastatic renal cell carcinoma: current treatment and future directions.

Project description:An understanding of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways has greatly changed the way metastatic renal cell carcinoma (RCC) is treated. Based on available phase III randomized trials, anti-VEGF agents such as sunitinib, sorafenib, bevacizumab-based therapy, and mTOR-targeted agents such as temsirolimus and everolimus have been used in the treatment armamentarium for this disease. Now that agents directed against these pathways have largely replaced immunotherapy as the standard of care, new questions have emerged and are the subject of ongoing clinical trials. The development of new targeted therapies including axitinib, pazopanib, cediranib, volociximab, tivozanib (AV-951), BAY 73-4506, and c-met inhibitors such as GSK1363089 and ARQ197 may potentially expand the list of treatment options. Sequential and combination targeted therapies are currently under investigation in advanced disease as are adjuvant and neo-adjuvant approaches around nephrectomy.

| S-EPMC3126007 | biostudies-literature

Overcoming endocrine resistance in metastatic breast cancer: Current evidence and future directions.

Project description:About 75% of all breast cancers are estrogen receptor (ER)-positive. They generally have a more favorable clinical behavior, prognosis, and pattern of recurrence, and endocrine therapy forms the backbone of treatment. Anti-estrogens (such as tamoxifen and fulvestrant) and aromatase inhibitors (such as anastrozole, letrozole, and exemestane) can effectively control the disease and induce tumor responses in a large proportion of patients. However, the majority of patients progress during endocrine therapy (acquired resistance) and a proportion of patients may fail to respond to initial therapy (de novo resistance). Endocrine resistance is therefore of clinical concern and there is great interest in strategies that delay or circumvent it. A deeper knowledge of the molecular mechanisms that drive endocrine resistance has recently led to development of new strategies that have the promise to effectively overcome it. Many resistance mechanisms have been described, and the crosstalk between ER and growth factor receptor signaling pathways seems to represent one of the most relevant. Compounds that are able to inhibit key elements of these pathways and restore endocrine sensitivity have been studied and more are currently under development. The aim of this review is to summarize the molecular pathophysiology of endocrine resistance in breast cancer and its impact on current clinical management.

| S-EPMC4259959 | biostudies-literature

Second-line treatment of metastatic gastric cancer: Current options and future directions.

Project description:Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase III trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.

| S-EPMC4631965 | biostudies-other

Ecological traps: current evidence and future directions.

Project description:Ecological traps, which occur when animals mistakenly prefer habitats where their fitness is lower than in other available habitats following rapid environmental change, have important conservation and management implications. Empirical research has focused largely on assessing the behavioural effects of traps, by studying a small number of geographically close habitat patches. Traps, however, have also been defined in terms of their population-level effects (i.e. as preferred habitats of sufficiently low quality to cause population declines), and this is the scale most relevant for management. We systematically review the ecological traps literature to (i) describe the geographical and taxonomic distribution of efforts to study traps, (ii) examine how different traps vary in the strength of their effects on preference and fitness, (iii) evaluate the robustness of methods being used to identify traps, and (iv) determine whether the information required to assess the population-level consequences of traps has been considered. We use our results to discuss key knowledge gaps, propose improved methods to study traps, and highlight fruitful avenues for future research.

| S-EPMC4760169 | biostudies-literature

Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China.

Project description:Lung cancer causes significant morbidity and mortality in China and worldwide. In China, lung cancer accounts for nearly one-fourth of all cancer deaths. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, accounting for approximately 80%-85% of all lung cancer cases. Immunotherapy with immune checkpoint inhibitors (ICIs) is revolutionizing the treatment of NSCLC. Immune checkpoint molecules, including PD-1/PD-L1 and CTLA-4, can suppress immune responses by delivering negative signals to T cells. By interfering with these immunosuppressive axes, ICIs unleash antitumor immune responses, ultimately eliminating cancer cells. ICIs have demonstrated promising antitumor efficacy in NSCLC, and mounting evidence supports the use of ICIs in treatment-naïve patients with advanced NSCLC. A comprehensive overview of current and emerging ICIs for the first-line treatment of NSCLC in China will facilitate a better understanding of NSCLC immunotherapy using ICIs and optimize the clinical use of ICIs in previously untreated Chinese patients with NSCLC. Herein, we review the efficacy and safety of currently approved and investigational ICIs as the first-line treatment of NSCLC in China. We also discuss the challenges limiting more widespread use of ICIs and future directions in the first-line treatment of NSCLC using ICIs.

| S-EPMC8654727 | biostudies-literature

Harnessing the PD-1 pathway in renal cell carcinoma: current evidence and future directions.

Project description:Programmed cell death-1 (PD-1) is a recognized immune checkpoint. It is frequently upregulated on the T cells that infiltrate tumors, providing an inhibitory signal, which may facilitate immune escape. Blocking antibodies have been developed to interrupt the interaction of PD-1 with its ligands PD-L1/PD-L2, with the goal of increasing the host antitumor immune response. Initial results have been encouraging, with durable responses in both treatment-naive and pretreated patients, along with an acceptable toxicity profile. This tolerability makes PD-1 blockade an excellent potential partner for combination strategies with the approved targeted agents, such as tyrosine kinase inhibitors (TKIs) and anti-vascular endothelial growth factor (anti-VEGF) antibodies, as well as other investigational immune checkpoint inhibitors or agonist antibodies that may costimulate an immune response. PD-L1 expression on tumor cells and tumor-infiltrating immune cells is also being evaluated as a predictive biomarker of response to treatment. This review summarizes the biological basis, preclinical studies, ongoing trials, and future challenges associated with targeting the PD-1 pathway in renal cell carcinoma.

| S-EPMC4888066 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data