Long-Term Disease Control With Sunitinib in a Patient With Metastatic Pancreatic Neuroendocrine Tumor (NET) Associated With Von Hippel-Lindau Syndrome (VHL)

Ali, Talha; Kandil, Dina; Piperdi, Bilal

doi:10.1097/mpa.0b013e31822a645e

Cited by 15 publications

(15 citation statements)

References 9 publications

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“…Recently, Ali et al [20] reported a long-term disease control with sunitinib in a VHL patient affected by pancreatic NET and sunitinib itself was granted approval for the treatment of sporadic pancreatic NET [21] as a proof of concept that angiogenic pathways targeted by sunitinib are deeply involved in the progression of NETs.…”

Section: Discussionmentioning

confidence: 98%

First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel–Lindau (VHL) disease: clinical outcome and patterns of radiological response

et al. 2014

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rate of radiological response, patterns of responses in different organs, treatment-related toxicities. We performed a retrospective analysis of sunitinib therapy in genetically-confirmed VHL patients treated at our Institution for multifocal or advanced RCC. From February 2007 to July 2012, 14 VHL patients started first-line sunitinib for recurrent or progressing RCC, mean age 48 years (27-71). Nine patients achieved a partial RECIST response (64.3%); responses were noted not only in renal and hepatic lesions but also in pancreatic nodules. Most lesions showed density reduction, while all CNS haemangioblastoma lesions remained stable. At a median follow-up of 37 months, six patients have progressed and three patients died, with a progression-free rate at 2 years of 71.4%. Sunitinib may therefore achieve a fairly good disease control in VHL patients. Radiological responses may be obtained not only in renal tumors but also in synchronous VHL-related lesions, especially pancreatic solid nodules whose exact nature (metastatic RCC or neuroendocrine tumor) cannot be ruled out without invasive biopsy.

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Section: Discussionmentioning

confidence: 98%

First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel–Lindau (VHL) disease: clinical outcome and patterns of radiological response

et al. 2014

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“…Currently, while anti-angiogenic agents have been investigated for treatment of renal cell carcinoma in VHL, therapy for other VHL-associated tumors (particularly hemangioblastomas) is surgery, which is linked to significant morbidity and mortality (Ali et al, 2012; Jonasch et al, 2011; Lonser et al, 2003). Consequently, new non-invasive, syndrome-specific, therapies are needed.…”

Section: Introductionmentioning

confidence: 99%

Proteostasis Modulators Prolong Missense VHL Protein Activity and Halt Tumor Progression

et al. 2013

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SUMMARY While missense mutations of von Hippel-Lindau disease (VHL) gene are the most common germline mutation underlying this heritable cancer syndrome, the mechanism of tumorigenesis is unknown. We found a quantitative reduction of missense mutant VHL protein (pVHL) in VHL-associated tumors associated with physiologic mRNA expression. While mutant pVHL is unstable and degraded contemporarily with translation, it retains its E3 ligase function, including hypoxia inducible factor degradation. The premature pVHL degradation is due to misfolding and imbalance of chaperonin binding. Histone deacetylase inhibitors (HDACis) can modulate this pathway by inhibiting the HDAC6-Hsp90 chaperone axis, stabilizing pVHL and restoring activity comparable to wild type protein in vitro and in animal models (786-O tumor xenografts). HDACi mediated stabilization of missense pVHL significantly attenuates the growth of 786-O rodent tumor model. These findings provide direct biologic insight into VHL-associated tumors and elucidate a new treatment paradigm for VHL.

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“…The first surgical option for sporadic HPT is to remove the single parathyroid adenoma (adenomectomy), whereas total parathyroidectomy (PTx) followed by a parathyroid implant in the forearm or sub-total PTx is used for HPT/MEN1 cases (49-52). In addition, sporadic insulinoma is frequently treated with surgery by single pancreatic nodule removal, whereas cases with insulinoma/MEN1 are usually submitted to sub-total pancreatectomy (83,117). For gastrinoma in MEN1, subtotal or total duodenopancreatectomy or subtotal pancreatectomy associated with duodenotomy is applied, and partial pancreatectomy is usually the surgical choice in sporadic gastrinoma (33,34,51,52).…”

Section: Introductionmentioning

confidence: 99%

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

Toledo¹,

Lourenço²,

Toledo³

2013

Clinics

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Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed.

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Long-Term Disease Control With Sunitinib in a Patient With Metastatic Pancreatic Neuroendocrine Tumor (NET) Associated With Von Hippel-Lindau Syndrome (VHL)

Cited by 15 publications

References 9 publications

First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel–Lindau (VHL) disease: clinical outcome and patterns of radiological response

First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel–Lindau (VHL) disease: clinical outcome and patterns of radiological response

Proteostasis Modulators Prolong Missense VHL Protein Activity and Halt Tumor Progression

A differential diagnosis of inherited endocrine tumors and their tumor counterparts

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