Update on targeted therapies for clear cell renal cell carcinoma

Singer, Eric A.; Gupta, Gopal N.; Srinivasan, Ramaprasad

doi:10.1097/cco.0b013e32834479c0

Cited by 58 publications

(44 citation statements)

References 48 publications

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“…In conclusion, metastatic RCC is generally associated with a poor prognosis (2); few patients experience long-term survival following surgery, and the clinical application of targeted drugs, including interferon immunotherapy, may improve patient survival (21). In the current case, the patient underwent simultaneous right nephrectomy, left adrenalectomy and segmental pancreatectomy, followed by receipt of interferon immunotherapy for 6 months.…”

Section: Discussionmentioning

confidence: 99%

Synchronous renal cell carcinoma metastasis to the contralateral adrenal gland and pancreas: A case report with 7-year follow-up subsequent to surgical therapy

Zhou

et al. 2016

Oncology Letters

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Abstract. Metastatic renal cell carcinoma (RCC) disseminates to a number of organ sites and few patients demonstrate long-term survival following surgery. However, synchronous metastasis of RCC to the contralateral adrenal gland and pancreas is rare. In the present report, a case of synchronous RCC metastasis to the contralateral adrenal gland and pancreas in a 55-year-old patient, with an 116x92x61 mm right renal tumor and a 96x79x57 mm left adrenal lesion, is described. In April 2007, right nephrectomy was performed to treat the RCC, left adrenalectomy was performed to treat the adrenal tumor and the pancreatic metastases were resected. The patient remained alive at the 7-year follow-up appointment. IntroductionNumerous patients with RCC remain asymptomatic until the late stages of the disease. The prevalence of the classic triad of flank pain, gross haematuria and a palpable abdominal mass is rare, while paraneoplastic syndromes occur in ~30% of patients with symptomatic RCCs. A small number of patients present with symptoms caused by metastatic RCC (1). Metastatic disease at diagnosis is observed in ~25-30% of patients with renal cell carcinoma (RCC), and <5% of patients exhibit solitary metastasis. The most common distant RCC metastasis sites are the lungs (50-60%), bone (30-40%), liver (30-40%) and brain (5%); however, metastasis may involve virtually any organ site (2). While adrenal metastasis from RCC to the ipsilateral adrenal gland is common, synchronous metastasis of RCC to the contralateral adrenal gland is rare, and affects only 0.51% of patients (6/1,179) (3). Pancreatic metastases from RCC are additionally rare (accounting for 1.5-3% of all metastatic RCC cases), and these cases typically present a number of years subsequent to the primary RCC diagnosis (4,5).For localised RCC, surgery is the only curative treatment with high-quality evidence and for metastatic RCC surgery is curative only if the total tumor burden can be removed (1). As prognosis is directly associated with the stage or degree of tumor dissemination, metastatic RCC generally equates to a poor prognosis for patients; indeed, response rates for treated patients remain low, at ~15-25%, with 5-year survival rates of 5-10% and overall median survival of <1 year (2). However, in certain cases, radical resection of metastases may prolong survival. In the present paper, a case of synchronous RCC metastasis to the contralateral adrenal gland and pancreas is reported. The patient remained alive at the final follow-up appointment, a total of 7 years subsequent to undergoing simultaneous right nephrectomy, left adrenalectomy and segmental pancreatectomy. Case reportA 55-year-old man with no relevant medical history visited the Transplantation Center of The First Affiliated Hospital at Wenzhou Medical University (Wenzhou, China) to undergo a routine physical examination in March 2007. Abdominal magnetic resonance imaging (MRI; 1.5T; GE Healthcare, Little Chalfont, UK) revealed a 99x81 mm right renal tumor and a 94x72 mm left adrenal lesion (...

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Section: Discussionmentioning

confidence: 99%

Synchronous renal cell carcinoma metastasis to the contralateral adrenal gland and pancreas: A case report with 7-year follow-up subsequent to surgical therapy

Zhou

et al. 2016

Oncology Letters

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“…In recent studies, the combination therapy of gemcitabine and S-1 has shown a better RR [9]. Sorafenib, a multitargeted kinase inhibitor, has been approved by the United States Food and Drug Administration (FDA) for the treatment of unresectable hepatocellular carcinoma [30] and advanced renal cell carcinoma [31]. However, another study showed that sorafenib did not produce a satisfactory RR for CCA treatment [32].…”

Section: Western Blotting Analysis For Signal Pathwaysmentioning

confidence: 98%

Optimal combination of gemcitabine, sorafenib, and S-1 shows increased efficacy in treating cholangiocarcinoma in vitro and in vivo

Zhang

Zhou

et al. 2016

Anti-Cancer Drugs

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Cholangiocarcinoma (CCA) is one of the most difficult cancers to treat and lacks an established standard chemotherapy regimen. This study evaluated the effects of different combinations of gemcitabine, sorafenib, and S-1 on CCA cells to identify the optimal drug combination. A fractional factorial design method was applied in drug combination experiments to determine the optimal combination of these three drugs (gemcitabine=1.4 mmol/l, sorafenib=0.03 mmol/l, S-1=0.185 mmol/l). We constructed a mathematical model with a small number of runs (Y=1.14-0.377A-23.0B-1.81C+0.084A+109B+6.06C+3.83AB+0.175AC-40.4BC) to predict the efficacy of combinations of the drugs. The optimal combination can significantly inhibit the AKT/mTOR pathway, and thus CCA cell proliferation, and can induce cell apoptosis. In vivo, this combination (gemcitabine=1.4 mmol/l, sorafenib=0.03 mmol/l, S-1=0.185 mmol/l) can significantly inhibit tumor growth. The present study showed that the mathematical model was reliable and could predict the efficacy of the different drug combinations. The optimal combination of these drugs may aid the development of a promising standard chemotherapy regimen for CCA.

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“…Despite considerable advances in our ability to manage advanced RCC, this disease continues to have a significant public health impact(1, 2). In the United States, RCC is currently the sixth and eighth most common malignancy among men and women, respectively, with 63,920 new cases and 13,860 deaths estimated in 2014(3).…”

Section: Introductionmentioning

confidence: 99%

Renal cell carcinoma

Stamatakis

Singer

et al. 2014

Current Opinion in Oncology

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Purpose of review Renal cell carcinoma (RCC) continues to be the subject of vigorous clinical and translational investigation. Advances in systemic targeted therapies, new molecular pathways, and immunotherapy approaches will be discussed. Recent findings Agents targeting the vascular endothelial growth factor (VEGF) and/or the mammalian target of rapamycin (mTOR) pathways continue to be the mainstay for treating metastatic RCC (mRCC). Although enhanced target specificity has improved the toxicity profile associated with newer VEGF-pathway antagonists, durable complete responses remain the exception. Identification of novel pathways/agents, as well as the optimal sequencing and combination of existing targeted agents, remain areas of active study. In addition, emerging data from early clinical trials has reinvigorated interest in immunomodulatory agents. Summary The therapeutic armamentarium available to genitourinary oncologists continues to grow but much work remains to be done to fully realize the potential of pathway-specific targeted strategies and immune-based approaches for mRCC.

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Update on targeted therapies for clear cell renal cell carcinoma

Cited by 58 publications

References 48 publications

Synchronous renal cell carcinoma metastasis to the contralateral adrenal gland and pancreas: A case report with 7-year follow-up subsequent to surgical therapy

Synchronous renal cell carcinoma metastasis to the contralateral adrenal gland and pancreas: A case report with 7-year follow-up subsequent to surgical therapy

Optimal combination of gemcitabine, sorafenib, and S-1 shows increased efficacy in treating cholangiocarcinoma in vitro and in vivo

Renal cell carcinoma

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