Related Experiment Video

Updated: Feb 7, 2026

Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
11:27

Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy

Published on: April 29, 2014

17.2K

Therapeutic Targeting of TFE3/IRS-1/PI3K/mTOR Axis in Translocation Renal Cell Carcinoma

Nur P Damayanti1, Justin A Budka2, Heba W Z Khella3

  • 1Genitourinary Program, Division of Hematology & Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|August 1, 2018
PubMed
Abstract

Insights

Translocation renal cell carcinoma (tRCC) is resistant to standard treatments. Targeting the TFE3/IRS-1/PI3K/AKT/mTOR pathway with dual inhibitors shows promise for tRCC drug development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney cancer.
  • tRCC is characterized by gene fusions (TFE3, TFEB, MITF) and is unresponsive to conventional treatments.
  • Novel therapeutic targets are urgently needed for tRCC.

Purpose of the Study:

  • To establish and characterize a patient-derived xenograft (PDX) model for tRCC drug development.
  • To identify and validate therapeutic targets within tRCC.
  • To assess the efficacy of targeting identified pathways in preclinical tRCC models.

Main Methods:

  • Next-generation sequencing and bioinformatics analysis of a tRCC PDX model (RP-R07).
  • RNA-sequencing (RNA-seq) and RT-PCR to identify gene fusions.
  • Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) and miRNA microarray analysis to identify enriched pathways.
  • In vitro and in vivo studies to assess therapeutic interventions.
  • Gene knockdown experiments.

Main Results:

  • A SFPQ-TFE3 fusion was identified in the RP-R07 model.
  • The PI3K/AKT/mTOR pathway was significantly enriched in tRCC models.
  • Dual inhibition of PI3K/AKT and mTOR demonstrated superior antiproliferative effects compared to single-agent inhibition.
  • TFE3 knockdown reduced IRS-1 expression and inhibited cell proliferation.

Conclusions:

  • The TFE3/IRS-1/PI3K/AKT/mTOR axis is a potential dysregulated pathway in TFE3-tRCC.
  • Vertical inhibition of this axis using dual PI3K/mTOR inhibitors represents a promising therapeutic strategy for tRCC.

More Related Videos

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction05:28

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction

Published on: August 27, 2019

17.7K
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane05:36

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

9.5K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.8K
Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
66.3K
Perpendicular-Axis Theorem01:16

Perpendicular-Axis Theorem

The perpendicular-axis theorem states that the moment of inertia of a planar object about an axis perpendicular to its plane is equal to the sum of the moments of inertia about two mutually perpendicular concurrent axes lying in the plane of the body.
Consider a circular disc of mass M and radius R lying along an x-y plane. The origin lies at the center of the disc, and the z-axis is perpendicular to the disc's plane. All three axes coincide at the disc's center. The moment of inertia of this...
4.6K
Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
10.0K
Parallel-axis Theorem01:06

Parallel-axis Theorem

The parallel-axis theorem provides a convenient and quick method of finding the moment of inertia of an object about an axis parallel to the axis passing through its center of mass. Consider a thin rod as an example. There is a striking similarity between the process of finding the moment of inertia of a thin rod about an axis through its middle, where the center of mass lies, and about an axis through its end using the conventional method. In the conventional method, the concept of linear mass...
8.3K