A Contemporary Review of Immune Checkpoint Inhibitors in Advanced Clear Cell Renal Cell Carcinoma

Yu, Eun-mi; Linville, Laura; Rosenthal, Matthew; Aragon‐Ching, Jeanny B.

doi:10.3390/vaccines9080919

Cited by 10 publications

(10 citation statements)

References 42 publications

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“…Interestingly, it has been demonstrated that G protein-coupled receptors (often overexpressed in HNC) ligands prostaglandin E2, bradykinin, and gastrin-releasing peptide activate EGFR signaling [ 125 , 126 , 127 ]. Another interesting therapeutic and prognostic target is the VEGF pathway (a member of the platelet-derived growth factor, PDGF, superfamily) [ 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 ], whose receptors are expressed both on endothelial cells and tumor cells and that include VEGF from A to E. VEGF (mainly VEGF-A) is often overexpressed in HNC and plays a key role as a mediator of angiogenesis, which supports tumorigenesis potentially modulating the tumor microenvironment [ 136 , 137 ]. On the other hand, hypoxia, one of the main components of the HNC microenvironment, is a major factor inducing VEGF expression through the expression of hypoxia-inducible factor-α (HIF-1α) [ 138 , 139 ].…”

Section: Head and Neck Cancer Etiopathogenesismentioning

confidence: 99%

Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents

et al. 2022

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Head and neck cancer (HNC) concerns more than 890,000 patients worldwide annually and is associated with the advanced stage at presentation and heavy outcomes. Alcohol drinking, together with tobacco smoking, and human papillomavirus infection are the main recognized risk factors. The tumorigenesis of HNC represents an intricate sequential process that implicates a gradual acquisition of genetic and epigenetics alterations targeting crucial pathways regulating cell growth, motility, and stromal interactions. Tumor microenvironment and growth factors also play a major role in HNC. Alcohol toxicity is caused both directly by ethanol and indirectly by its metabolic products, with the involvement of the oral microbiota and oxidative stress; alcohol might enhance the exposure of epithelial cells to carcinogens, causing epigenetic modifications, DNA damage, and inaccurate DNA repair with the formation of DNA adducts. Long-term markers of alcohol consumption, especially those detected in the hair, may provide crucial information on the real alcohol drinking of HNC patients. Strategies for prevention could include food supplements as polyphenols, and alkylating drugs as therapy that play a key role in HNC management. Indeed, polyphenols throughout their antioxidant and anti-inflammatory actions may counteract or limit the toxic effect of alcohol whereas alkylating agents inhibiting cancer cells’ growth could reduce the carcinogenic damage induced by alcohol. Despite the established association between alcohol and HNC, a concerning pattern of alcohol consumption in survivors of HNC has been shown. It is of primary importance to increase the awareness of cancer risks associated with alcohol consumption, both in oncologic patients and the general population, to provide advice for reducing HNC prevalence and complications.

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Section: Head and Neck Cancer Etiopathogenesismentioning

confidence: 99%

Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents

et al. 2022

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“…In recent years, researchers have found that targeted therapy combined with immunotherapy has beneficial treatment effects and good prospects in patients with advanced KIRC, and has shown a trend of gradually replacing targeted therapy alone (9). However, many patients do not benefit from the combined therapy because of the overlapping drug toxicity that affects their quality of life (10). Therefore, new molecular phenotypes should be established to divide the population more finely for the individualized selection of effective immunotherapy drugs or targeted drugs for patients with advanced or unresectable KIRC.…”

Section: Introductionmentioning

confidence: 99%

Cuproptosis status affects treatment options about immunotherapy and targeted therapy for patients with kidney renal clear cell carcinoma

et al. 2022

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The development of immunotherapy has changed the treatment landscape of advanced kidney renal clear cell carcinoma (KIRC), offering patients more treatment options. Cuproptosis, a novel cell death mode dependent on copper ions and mitochondrial respiration has not yet been studied in KIRC. We assembled a comprehensive cohort of The Cancer Genome Atlas (TCGA)-KIRC and GSE29609, performed cluster analysis for typing twice using seven cuproptosis-promoting genes (CPGs) as a starting point, and assessed the differences in biological and clinicopathological characteristics between different subtypes. Furthermore, we explored the tumor immune infiltration landscape in KIRC using ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) and the potential molecular mechanisms of cuproptosis in KIRC using enrichment analysis. We constructed a cuproptosis score (CUS) using the Boruta algorithm combined with principal component analysis. We evaluated the impact of CUS on prognosis, targeted therapy, and immunotherapy in patients with KIRC using survival analysis, the predictions from the Cancer Immunome Atlas database, and targeted drug susceptibility analysis. We found that patients with high CUS levels show poor prognosis and efficacy against all four immune checkpoint inhibitors, and their immunosuppression may depend on TGFB1. However, the high-CUS group showed higher sensitivity to sunitinib, axitinib, and elesclomol. Sunitinib monotherapy may reverse the poor prognosis and result in higher progression free survival. Then, we identified two potential CPGs and verified their differential expression between the KIRC and the normal samples. Finally, we explored the effect of the key gene FDX1 on the proliferation of KIRC cells and confirmed the presence of cuproptosis in KIRC cells. We developed a targeted therapy and immunotherapy strategy for advanced KIRC based on CUS. Our findings provide new insights into the relationship among cuproptosis, metabolism, and immunity in KIRC.

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“…Patient preferences may be influenced by several different variables, including treatment schedule, treatment-related toxicities, management options for these potential toxicities, and whether the approach would be covered by the patient’s insurance provider [ 34 , 35 ]. For instance, pembrolizumab can be given every 6 weeks as opposed to every 4 weeks with nivolumab therapy—making pembrolizumab a preferred drug for patients who face a distance barrier to accessing an infusion center.…”

Section: Current First Line Standard Of Carementioning

confidence: 99%

Metastatic Clear-Cell Renal Cell Carcinoma in the Era of Immune Checkpoint Inhibitors: Therapies and Ongoing Trials

Zhuang

Case

Olsen

et al. 2022

Cancers

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Immune checkpoint inhibitors (ICI) are now the bedrock for the treatment of metastatic renal cell carcinoma (RCC). Clear cell RCC (ccRCC) represents the most common subtype of this malignancy. Herein, we explore the therapeutic landscape of ccRCC by discussing the standard of care whose backbone consists of immune checkpoint inhibitors (ICI) and vascular endothelial growth factor inhibitors (VEGF). For ccRCC, pembrolizumab-axitinib, pembrolizumab-lenvatinib, and avelumab-axitinib or nivolumab-cabozantinib are now FDA-approved frontline options for all risk groups while nivolumab-ipilimumab is reserved for intermediate- and poor-risk groups. Monotherapy with pembrolizumab or nivolumab is a potential option for patients who are unable to take VEGFR-tyrosine kinase inhibitors. While outcomes have improved with the adoption of ICI therapies, many patients develop therapy-resistant disease, creating an unmet need for further investigation. The efficacy of novel therapies as well as novel combinations in the post-ICI era is unclear. This review summarizes the most significant clinical trials involving dual ICI/ICI and ICI/VEGFR therapies, in addition to other selected combination therapies that are likely to inform management in the near future.

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A Contemporary Review of Immune Checkpoint Inhibitors in Advanced Clear Cell Renal Cell Carcinoma

Cited by 10 publications

References 42 publications

Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents

Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents

Cuproptosis status affects treatment options about immunotherapy and targeted therapy for patients with kidney renal clear cell carcinoma

Metastatic Clear-Cell Renal Cell Carcinoma in the Era of Immune Checkpoint Inhibitors: Therapies and Ongoing Trials

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