An update on current management of advanced renal cell cancer, biomarkers, and future directions

Zhi, Wanqing Iris; Kim, Jaeyeon

doi:10.7243/2049-7962-3-8

Cited by 6 publications

(4 citation statements)

References 93 publications

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“…3,4 Over the past decade, new therapies targeting VEGF, tyrosine kinase and mTOR pathways have improved PFS and OS. 5 However, an OS benefit over the previous standard of care, such as interferon, could not been shown in most of the clinical trials of first-line treatment, and regulatory approval had been based on PFS benefit. 6 OS in patients with mRCC has doubled over the past decade, largely due to the availability and sequencing of these agents.…”

Section: Introductionmentioning

confidence: 99%

Treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma in Japan

et al. 2018

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Objectives To clarify treatment patterns and outcomes for patients with unresectable or metastatic renal cell carcinoma in the molecular target therapy era in Japan. Methods A multicenter, retrospective medical chart review study was carried out. Patients diagnosed with unresectable or metastatic renal cell carcinoma between January 2012 and August 2015 were enrolled. Data extracted from medical records included treatment duration, grade ≥3 adverse events, reason for discontinuation for each targeted therapy and survival data until August 2016. Results Of 277 eligible patients, 266, 170 and 77 received first‐, second‐ and third‐line systemic treatment, respectively. Tyrosine kinase inhibitors were the most common first‐line therapy (72.2%), followed by mammalian target of rapamycin inhibitors (14.3%) and cytokines (13.5%). Among 170 patients who received second‐line treatment, tyrosine kinase inhibitor–tyrosine kinase inhibitor was the most common sequence (58.8%), followed by tyrosine kinase inhibitor–mammalian target of rapamycin inhibitor (14.1%) and cytokine–tyrosine kinase inhibitor (14.1%). With a median follow‐up period of 19.8 months, median overall survival was not reached at 48 months. Patients who discontinued first‐line tyrosine kinase inhibitors in <6 months showed poorer overall survival compared with patients who received first‐line tyrosine kinase inhibitors for ≥6 months. Conclusions The present analysis illustrates the contemporary treatment patterns and prognosis for patients with unresectable or metastatic renal cancer in a real‐world setting in Japan. Tyrosine kinase inhibitor–tyrosine kinase inhibitor represents the most commonly used sequence. Shorter treatment duration of first‐line tyrosine kinase inhibitors is associated with poorer prognosis, suggesting the need for better treatment options.

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Section: Introductionmentioning

confidence: 99%

Treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma in Japan

et al. 2018

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“…The only molecular mechanism related to RTKs in ccRCCs is dysregulation of the pVHL/HIF axis [14, 15], which drives expression of VEGF and PDGFβ and, hence, activation of their receptors VEGFR2 and PDGFRβ [16–20]. Therefore, current treatments for ccRCCs are mostly anti-angiogenic tyrosine-kinase inhibitors (TKIs) targeting VEGFR, which include pazopanib, sunitinib, axitinib, sorafenib, and bevacizumab [21, 22].…”

Section: Introductionmentioning

confidence: 99%

Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas

Zhang

Liu

et al. 2019

BMC Cancer

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BackgroundThe receptor tyrosine kinases (RTKs) play critical roles in the development of cancers. Clear cell renal cell carcinoma (ccRCC) accounts for 75% of the RCC. The previous studies on the RTKs in ccRCCs mainly focused on their gene expressions. The activation and function of the RTKs in ccRCC have not been fully investigated.MethodsIn the present study, we analyzed the phosphorylation patterns of RTKs in human ccRCC patient samples, human ccRCC and papillary RCC cell lines, and other kidney tumor samples using human phospho-RTK arrays. We further established ccRCC patient-derived xenograft models in nude mice and assessed the effects of RTKIs (RTK Inhibitors) on the growth of these cancer cells. Immunofluorescence staining was used to detect the localization of keratin, vimentin and PDGFRβ in ccRCCs.ResultsWe found that the RTK phosphorylation patterns of the ccRCC samples were all very similar, but different from that of the cell lines, other kidney tumor samples, as well as the adjacent normal tissues. 9 RTKs, EGFR1–3, Insulin R, PDGFRβ, VEGFR1, VEGFR2, HGFR and M-CSFR were found to be phosphorylated in the ccRCC samples. The adjacent normal tissues, on the other hand, had predominantly only two of the 4 EGFR family members, EGFR and ErbB4, phosphorylated. What’s more, the RTK phosphorylation pattern of the xenograft, however, was different from that of the primary tissue samples. Treatment of the xenograft nude mice with corresponding RTK inhibitors effectively inhibited the Erk1/2 signaling pathway as well as the growth of the tumors. In addition, histological staining of the cancer samples revealed that most of the PDGFRβ expressing cells were localized in the vimentin-positive periepithelial stroma.ConclusionsOverall, we have identified a set of RTKs that are characteristically phosphorylated in ccRCCs. The phosphorylation of RTKs in ccRCCs were determined by the growing environments. These phosphorylated/activated RTKs will guide targeting drugs development of more effective therapies in ccRCCs. The synergistical inhibition of RTKIs combination on the ccRCC suggest a novel strategy to use a combination of RTKIs to treat ccRCCs.

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“…As a result, the standard treatment has shifted from immunotherapy (IT) to targeted therapy (TT), in which interferon (IFN)-α in combination with other TTs and interleukin (IL)-2 alone are utilized as first-line systemic therapies in selected metastatic RCC (mRCC) patients [ 3 ]. However, the prognosis of advanced RCC remains disappointing; stages III and IV RCC have 60% and 10% 5-year disease-specific survival rates, respectively, in spite of such treatments [ 4 ]. While improved OS trends mirror those of PFS, the survival benefit from TT is still limited, with a median of less than 2–3 years, and is often not statistically significant.…”

Section: Introductionmentioning

confidence: 99%

Initial computed tomography imaging details during first-line systemic therapy is of significant prognostic value in patients with naïve, unresectable metastatic renal cell carcinoma

et al. 2017

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PurposeWe aimed to determine the prognostic significance of computed tomography imaging parameters of unresectable primary renal tumor lesions, obtained at baseline and at first follow-up, on overall survival in naïve, unresectable metastatic renal cell carcinoma patients during first-line systemic therapy.Materials and methodsClinicopathological parameters of 56 patients treated between 2007 and 2015, including imaging parameters (such as the longest tumor diameter, necrotic area diameter, and attenuation in primary renal tumor lesions on baseline vs. follow-up computed tomography), were retrospectively reviewed to derive predictive factors of overall survival. The best overall response was measured according to the RECIST v1.1.ResultsThe median treatment period was 206.3 days and the median follow-up was 14.6 months. Forty-four (78.6%) patients progressed after a median 4.6 months of progression-free survival, and 6 (10.7%) patients survived with a median overall survival of 12.5 months. Multivariate analysis showed that the baseline tumor diameter (hazard ratio [HR] 0.903) and mean attenuation (HR 0.936), change of tumor diameter (HR 0.714) and necrosis diameter (HR 0.861), change in the percentage of tumor diameter (HR 1.483) and of necrosis diameter (HR 1.028) between baseline and follow-up computed tomography images; treatment duration (HR 0.986) and baseline serum hemoglobin (HR 1.790) and albumin level (HR 0.060) were significant factors for overall survival (p<0.05).ConclusionThe study showed that baseline and first follow-up computed tomography findings of primary renal lesions during first-line systemic therapy are useful and significant predictors of OS in patients with naïve unresectable mRCC.

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An update on current management of advanced renal cell cancer, biomarkers, and future directions

Cited by 6 publications

References 93 publications

Treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma in Japan

Treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma in Japan

Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas

Initial computed tomography imaging details during first-line systemic therapy is of significant prognostic value in patients with naïve, unresectable metastatic renal cell carcinoma

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