Systemische und operative Therapie des metastasierten Nierenzellkarzinoms

Kramer, Mario W.; Merseburger, Axel S.; Peters, Inga; Waalkes, Sandra; Kuczyk, Markus A.

doi:10.1007/s00120-011-2713-5

Cited by 2 publications

(1 citation statement)

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“…Last but not least, the (perhaps not resectable) primary tumor can deteriorate further. This can be associated with symptoms and may require procedures that directly burdens the individual patient [21,22]. PFS per se is of immediate, clinically and patient-relevant value in these patients [23].…”

Section: Reviewmentioning

confidence: 99%

Patient relevant endpoints in oncology: current issues in the context of early benefit assessment in Germany

et al. 2014

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The German AMNOG healthcare reform includes a mandatory early-benefit-assessment (EBA) at launch. As per German social code, EBA is based on registration trials and includes evaluation of the patient-relevant effect of the new medicines compared to an appropriate comparator as defined by the Federal Joint Committee (G-BA). Current EBA decisions released have unveiled issues regarding the acceptance of some patient-relevant endpoints as G-BA and IQWiG are grading the endpoints, focusing on overall survival as the preferred endpoint in oncology.A taskforce of experienced German outcomes research, medical, health-technology assessment and biostatistics researchers in industry was appointed. After agreement on core assumptions, a draft position was prepared. Input on iterative versions was solicited from a panel of reviewers from industry and external stakeholders.Distinctive features of registration trials in oncology need to be considered when these studies form basis for EBA, especially in cancer-indications with long post-progression survival; and with several consecutive therapeutic options available post-progression. Ethical committees, caregivers and patients often demand cross-over-designs diluting the treatment-effect on overall survival. Regulatory authorities require evaluation of morbidity-related study endpoints including survival of patients without their disease getting worse (i.e., progression-free survival). Also, progression requires treatment-changes, another strong indicator for its relevance to patients.Based on specific guidelines and clinical trial programs that were developed to be consistent with regulatory guidance, endpoints in oncology are thoroughly evaluated in terms of their patient-relevance. This extensive knowledge and experience should be fully acknowledged during EBA when assessing the patient-relevant benefit of innovative medicines in oncology.JEL codesD61; H51; I18.

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Section: Reviewmentioning

confidence: 99%

Patient relevant endpoints in oncology: current issues in the context of early benefit assessment in Germany

et al. 2014

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Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma

Ajadee,

Mahmud,

Hossain

et al. 2024

PLoS ONE

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Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of kidney cancer. Although there is increasing evidence linking ccRCC to genetic alterations, the exact molecular mechanism behind this relationship is not yet completely known to the researchers. Though drug therapies are the best choice after the metastasis, unfortunately, the majority of the patients progressively develop resistance against the therapeutic drugs after receiving it for almost 2 years. In this case, multi-targeted different variants of therapeutic drugs are essential for effective treatment against ccRCC. To understand molecular mechanisms of ccRCC development and progression, and explore multi-targeted different variants of therapeutic drugs, it is essential to identify ccRCC-causing key genes (KGs). In order to obtain ccRCC-causing KGs, at first, we detected 133 common differentially expressed genes (cDEGs) between ccRCC and control samples based on nine (9) microarray gene-expression datasets with NCBI accession IDs GSE16441, GSE53757, GSE66270, GSE66272, GSE16449, GSE76351, GSE66271, GSE71963, and GSE36895. Then, we filtered these cDEGs through survival analysis with the independent TCGA and GTEx database and obtained 54 scDEGs having significant prognostic power. Next, we used protein-protein interaction (PPI) network analysis with the reduced set of 54 scDEGs to identify ccRCC-causing top-ranked eight KGs (PLG, ENO2, ALDOB, UMOD, ALDH6A1, SLC12A3, SLC12A1, SERPINA5). The pan-cancer analysis with KGs based on TCGA database showed the significant association with different subtypes of kidney cancers including ccRCC. The gene regulatory network (GRN) analysis revealed some crucial transcriptional and post-transcriptional regulators of KGs. The scDEGs-set enrichment analysis significantly identified some crucial ccRCC-causing molecular functions, biological processes, cellular components, and pathways that are linked to the KGs. The results of DNA methylation study indicated the hypomethylation and hyper-methylation of KGs, which may lead the development of ccRCC. The immune infiltrating cell types (CD8+ T and CD4+ T cell, B cell, neutrophil, dendritic cell and macrophage) analysis with KGs indicated their significant association in ccRCC, where KGs are positively correlated with CD4+ T cells, but negatively correlated with the majority of other immune cells, which is supported by the literature review also. Then we detected 10 repurposable drug molecules (Irinotecan, Imatinib, Telaglenastat, Olaparib, RG-4733, Sorafenib, Sitravatinib, Cabozantinib, Abemaciclib, and Dovitinib.) by molecular docking with KGs-mediated receptor proteins. Their ADME/T analysis and cross-validation with the independent receptors, also supported their potent against ccRCC. Therefore, these outputs might be useful inputs/resources to the wet-lab researchers and clinicians for considering an effective treatment strategy against ccRCC.

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Systemische und operative Therapie des metastasierten Nierenzellkarzinoms

Cited by 2 publications

References 50 publications

Patient relevant endpoints in oncology: current issues in the context of early benefit assessment in Germany

Patient relevant endpoints in oncology: current issues in the context of early benefit assessment in Germany

Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma

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