Therapeutic approach guided by genetic alteration: Use of MTOR inhibitor in renal medullary carcinoma with loss of PTEN expression

Lipkin, Jacob S.; Rizvi, Syed A.; Gatalica, Zoran; Sarwani, Nabeel; Holder, Sheldon L.; Kaag, M.; Joshi, Monika

doi:10.4161/15384047.2014.972843

Cited by 14 publications

(10 citation statements)

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“…This has downstream effects on overexpression of EZH2 (a histone methyltransferase), providing the rationale for using EZH2 inhibitors, such as tazemetostat, as therapeutic options . Phosphatase and tensin homologue (PTEN) loss and use of mammalian target of rapamycin (mTOR) inhibitors has also been under recent investigation, although results have been limited . As we gain insights into the biology of this aggressive tumour, we hope to develop novel and more effective therapies that will lead to improved patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study

et al. 2016

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“…For such tumors, the tyrosine kinase inhibitor sunitinib and the mTOR inhibitor everolimus have shown antitumor effects and improved prognosis [7][8][9]. Notably, low PTEN expression is also linked with clinical outcomes in patients with pancreatic NEN [10] and with sensitivity to mTOR inhibitors in other solid cancers [11,12]. However, the use of mTOR inhibitors has been limited only to advanced pancreatic NENs.…”

Section: Introductionmentioning

confidence: 99%

Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin

et al. 2016

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Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy.

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“…In the era of guided therapy and knowledge about driver mutation, a case report showed a patient treated with Everolimus (an MTOR inhibitor) maintenance after induction chemotherapy regimen of PCG (Paclitaxel Cisplatin-Gemcitabine) based on results of PTEN deficiency expressed in molecular profiling and next generation sequencing. This patient responded to induction therapy, had complete remission and remained in remission for seven month [23]. Other potential new drugs to be considered are histone deacetylase inhibitors, which have shown activity against malignant rhabdoid tumor cell lines [24].…”

Section: Discussionmentioning

confidence: 97%

RMC (Renal Medullary Cancer): A Case Report and Literature Review

Taranto¹,

Mariano²,

Eiger³

et al. 2016

JPP

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RMC (renal medullary carcinoma) is considered a rare entity, corresponding to approximately 2% of primary kidney tumors, usually occurring in the second decade of the patient's life and it is closely related with previous history of sickle cell disease. Studies have reported RMC as highly aggressive, poorly responsive to chemotherapy, surgery, radiotherapy or targeted therapy. This disease's median overall survival is less than 12 months. We are reporting a case of a 21-year-old woman with sickle cell trait, whose initial clinical presentation was RMC already metastatic to the liver. She underwent total right nephrectomy, and her clinical picture worsened during hospitalization with pneumonia, bowel obstruction, oliguria and death in less than two months after diagnosis, with no performance status to attempt any treatment options to her cancer at any time. Although some cases in the literature had reported good response to neoadjuvant therapy, this disease has early recurrence and little response to treatment. Our objective is to call the attention for this aggressive desease to estimulate new perspectives and further studies with chemotherapy and other different kinds of treatment, mainly because only surgical intervention is an incomplete aproach.

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Therapeutic approach guided by genetic alteration: Use of MTOR inhibitor in renal medullary carcinoma with loss of PTEN expression

Cited by 14 publications

References 25 publications

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study

Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin

RMC (Renal Medullary Cancer): A Case Report and Literature Review

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