Targeted therapies and complete responses in first line treatment of metastatic renal cell carcinoma. A meta-analysis of published trials

Iacovelli, Roberto; Adami, Daniele; Palazzo, Antonella; Trenta, Patrizia; Santoni, Matteo; Marchis, Laura De; Cascinu, Stefano; Naso, Giuseppe; Cortesi, Enrico

doi:10.1016/j.ctrv.2013.09.003

Cited by 83 publications

(62 citation statements)

References 47 publications

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“…The influence of CAFs on the migration ability of RCC cells was analyzed in our study. In the majority of patients with RCC, targeted therapies do not produce complete responses, and most individuals eventually come in few months refractory to treatment [15]. During the last years, mTOR inhibitors exert antitumor effects on several malignancies, but also has open the opportunity to induce new and unknown mechanisms of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated fibroblasts promote renal cell carcinoma progression

Song

et al. 2015

Tumor Biol.

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The aim of this study was to determine the effect of cancer-associated fibroblasts (CAFs) on renal cell carcinoma (RCC) tumor proliferation, migration, and development of drug resistance, thus underlying their potential as therapeutic targets in RCC patients. CAFs were grown in primary cultures. The in vitro model of interaction of RCC cell lines with CAFs was established. The influence of CAFs on the proliferation and migration ability as well as sensitivity to everolimus of RCC cells was further analyzed. Furthermore, Western blotting analysis was performed to examine the mechanisms mediating the effect of CAFs on RCC cells. The results of the MTT assay showed that coculture with CAFs increased the proliferation activity of both 786-O and Caki-1 cells compared with serum-free medium controls. The migration ability of RCC cell lines was also significantly enhanced after coculture treatment compared with untreated control. The inhibition effect of everolimus on 786-O and Caki-1 cells abrogated in cocultures with CAFs. The sensitivity of both two cell lines to everolimus was dramatically decreased when cocultured with CAFs. RCC cells cocultured with CAFs resulted in the activation of both proliferation-related (Erks) and survival-related (Akt) pathways. These data indicate that CAFs have an important role in supporting and promoting RCC. The interaction of CAFs with RCC cell lines stimulates tumor cell proliferation and migration and induces resistance to everolimus in RCC cells, suggesting that target of the tumor microenvironment may be a novel targeted therapies for RCC.

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Section: Discussionmentioning

confidence: 99%

Cancer-associated fibroblasts promote renal cell carcinoma progression

Song

et al. 2015

Tumor Biol.

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“…RCC, caused by mutations in renal tubular cells, is one of the most common urologic neoplasms (15). Increasing research has focused on the development of comprehensive treatments for RCC (16,17). The present study demonstrated the synergistic effects between cellular immunotherapy and lenvatinib in a murine model of RCC and the landscape of current targeted and cellular immunotherapy for RCC was examined.…”

Section: Introductionmentioning

confidence: 59%

Preclinical trial of the multi-targeted lenvatinib in combination with cellular immunotherapy for treatment of renal cell carcinoma

Cai

Tang

Shen

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Lenvatinib is an oral, multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor β, RET and KIT. Cellular immunotherapy has the potential to be a highly targeted treatment, with low toxicity to normal tissues and a high capacity to eradicate tumor tissue. The present study assessed the safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lenvatinib and cellular immunotherapy in a murine model of renal cell carcinoma (RCC). The present study used a therapeutic dose of 0.12 mg lenvatinib and/or 10 4 rat uterine cancer adenocarcinoma (RuCa)-sensitized lymphocytes administered once daily continuously in 7-day cycles. Tumor regression was observed in mice with RCC following treatment with lenvatinib and 10 4 RuCa-sensitized lymphocytes. MTD was established as once daily administration of 0.18 mg lenvatinib and 10 6 RuCa-sensitized lymphocytes. The most common treatment-related adverse effects observed were fatigue (40%), mucosal inflammation (30%), proteinuria, diarrhea, vomiting, hypertension and nausea (all 40%). Combination therapy using lenvatinib and cellular immunotherapy enhanced the antitumor effect induced by single treatments and prolonged the survival of mice with RCC compared with either of the single treatments. Treatment with lenvatinib (0.12 mg) combined with 10 4

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“…Several targeted therapy drugs, such as sunitinib, sorafenib, bevacizumab and temsirolimus, have been approved for use in patients with RCC (20). However, in addition to cytotoxic drugs, molecular targeting agents, including mammalian target of rapamycin inhibitors and tyrosine kinase receptors, have recently been introduced for the treatment of patients with RCC, and a survival benefit has been demonstrated in certain clinical trials (21,22).…”

Section: Discussionmentioning

confidence: 99%

Mediastinal lymph node metastasis of renal cell carcinoma: A case report

et al. 2016

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Abstract. Renal cell carcinoma (RCC) may metastasize to mediastinal lymph nodes without any abdominal lymph node involvement. The present study describes an autopsy-proven case of RCC presenting with a large mediastinal mass; the case had been previously misdiagnosed as small cell lung carcinoma due to imaging analysis results, an elevated serum level of neuron-specific enolase and the presence of small atypical cells with a high nuclear/cytoplasmic ratio. Despite RCC occurrence being rare, it should be considered in the differential diagnosis, particularly when a mass located in the kidneys presents with metastases to the mediastinal lymph nodes, even if there is no involvement of the abdominal lymph nodes and the primary lesion is of a small size. IntroductionRenal cell carcinoma (RCC) accounts for 95% of renal neoplasms and ~3% of adult malignancies (1). In the United States, ~61,560 patients with RCC were identified and 14,080 patients were predicted to have succumbed to the disease in 2015 (2). Generally, patients with RCC present with gross hematuria, flank pain and a palpable mass; however, these symptoms are not always present. RCC is a heterogeneous disease and several histological subtypes have been categorized according to the 2004 World Health Organization (WHO) renal tumor classification (3). The mortality rate of patients with RCC depends on the histological subtype and the clinical stage of the tumor. Since RCC has a hemorrhagic tendency, biopsy of the tumor is disputed (4). A diagnosis of RCC is provided according to the results observed using imaging methodologies, including computed tomography (CT), and a diagnosis of RCC is confirmed by the surgical removal of the tumor en bloc. The present study reports the case of a patient who presented with a large, right mediastinal mass appearing to mimic small cell lung cancer (SCLC); however, following autopsy examination, the diagnosis was confirmed as RCC. Case reportA 56-year-old male presented at the Ryugasaki Saiseikai Hospital (Ryugasaki, Japan) in September 2011 with a dry cough that had persisted for 3 months. Physical examination identified decreased breath sounds at the right hemithorax. Laboratory evaluations were undertaken and included urinalysis and testing of blood urea nitrogen, creatinine and serum calcium concentrations. All laboratory analyses were normal, with the exception of an increased concentration of white blood cells (12,100 cells/µl; normal range, 3,900-9,800 cells/µl), C-reactive protein (12.9 mg/dl; normal range, 0.0-0.3 mg/dl) and serum neuron-specific enolase (NSE; 50.0 ng/ml; normal range, 0.0-16.3 ng/ml). Following a CT scan of the chest, a large mass was detected at the right mediastinum, extending directly to the heart, with the presence of pericardial fluid (Fig. 1). Pleural fluid was identified in the right hemithorax, but no abnormalities were observed in the lungs and the abdominal lymph nodes were not swollen. However, a small nodule was detected in the upper pole of the right kidney. A bronchoscopy was performe...

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Targeted therapies and complete responses in first line treatment of metastatic renal cell carcinoma. A meta-analysis of published trials

Cited by 83 publications

References 47 publications

Cancer-associated fibroblasts promote renal cell carcinoma progression

Cancer-associated fibroblasts promote renal cell carcinoma progression

Preclinical trial of the multi-targeted lenvatinib in combination with cellular immunotherapy for treatment of renal cell carcinoma

Mediastinal lymph node metastasis of renal cell carcinoma: A case report

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