Related Experiment Video

Updated: May 26, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

835

STX17-DT facilitates axitinib resistance in renal cell carcinoma by inhibiting mitochondrial ROS accumulation and

Yihui Pan1, Shuang Liu2, Guannan Shu3,4

  • 1Department of Urology, the Third Affiliated Hospital of Soochow University, Changzhou, China. panyihui0314@163.com.

Cell Death & Disease
|February 23, 2025
PubMed

Insights

A novel long non-coding RNA, STX17-DT, drives axitinib resistance in advanced renal cell carcinoma (RCC) by altering cell metabolism and spreading resistance via extracellular vesicles. Targeting STX17-DT offers a new strategy to overcome therapy resistance in RCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Axitinib resistance is a significant obstacle in treating advanced renal cell carcinoma (RCC).
  • The molecular mechanisms underlying axitinib resistance in RCC are not fully elucidated.
  • Identifying novel therapeutic targets is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of long non-coding RNAs (lncRNAs) in axitinib resistance in RCC.
  • To identify specific lncRNAs that drive or mediate resistance to axitinib therapy.
  • To explore potential therapeutic strategies targeting identified resistance mechanisms.

Main Methods:

  • Construction of an in vivo axitinib-resistant RCC model.
  • Expression analysis of lncRNAs in resistant and sensitive RCC cells.
  • In vitro and in vivo validation of STX17-DT's role in axitinib resistance.
  • Mechanistic studies involving mRNA stability, reactive oxygen species (ROS), and ferroptosis.
  • Investigation of extracellular vesicle-mediated transfer of resistance.

Main Results:

  • STX17-DT expression was significantly upregulated in axitinib-resistant RCC cells and associated with poor prognosis.
  • Elevated STX17-DT promoted axitinib resistance both in vitro and in vivo.
  • STX17-DT stabilized IFI6 mRNA via hnRNPA1, reducing ROS and ferroptosis.
  • STX17-DT was packaged into extracellular vesicles, conferring resistance to other cells.
  • Combined axitinib and STX17-DT-targeted siRNA therapy showed enhanced efficacy.

Conclusions:

  • STX17-DT is a key driver of axitinib resistance in advanced RCC.
  • STX17-DT mediates resistance by modulating cellular metabolism and intercellular communication.
  • STX17-DT represents a promising prognostic biomarker and therapeutic target for overcoming axitinib resistance in RCC.

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

14.8K
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.6K

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
10.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.4K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K