Related Experiment Video

Updated: May 17, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

CRM1 blockade by selective inhibitors of nuclear export attenuates kidney cancer growth

Hiromi Inoue1, Michael Kauffman, Sharon Shacham

  • 1Division of Nephrology, Department of Internal Medicine, University of California-Davis, Davis, California 95616, USA.

The Journal of Urology
|October 20, 2012
PubMed
Abstract

Insights

CRM1 inhibitors show promise for treating advanced renal cell carcinoma (RCC). These compounds effectively reduced tumor growth and increased cancer cell death in preclinical models, offering a potential new therapeutic avenue for this challenging disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Renal cell carcinoma (RCC) is often diagnosed at the metastatic stage, with limited treatment options and poor survival rates.
  • Current therapies for metastatic RCC have short progression-free survival (1-2 years) and high resistance rates, necessitating novel therapeutic targets.
  • The nuclear exporter protein CRM1 is identified as a potential novel therapeutic target for RCC.

Purpose of the Study:

  • To evaluate the efficacy of CRM1 inhibitors KPT-185 and KPT-251 as a novel therapy for renal cell carcinoma.
  • To investigate the effects of CRM1 inhibition on cancer cell apoptosis, cell cycle arrest, and tumor suppressor protein localization.

Main Methods:

  • Testing KPT-185 and KPT-251 in multiple RCC cell lines and a xenograft model.
  • Quantifying apoptosis and cell cycle arrest using standard techniques.
  • Assessing the nuclear localization of p53 family proteins.

Main Results:

  • KPT-185 demonstrated increased cytotoxicity, apoptosis, and cell cycle arrest in RCC cells in vitro.
  • CRM1 inhibition by KPT-185 led to nuclear retention of tumor suppressor proteins p53 and p21.
  • Oral administration of KPT-251 significantly inhibited tumor growth in a high-grade RCC xenograft model with no apparent toxicity.

Conclusions:

  • CRM1 inhibitor proteins represent a novel therapeutic target for renal cell carcinoma.
  • Further intensive investigation of CRM1 inhibitors is warranted for RCC and other urological malignancies.

More Related Videos

Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy11:27

Modeling Spontaneous Metastatic Renal Cell Carcinoma (mRCC) in Mice Following Nephrectomy

Published on: April 29, 2014

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

Related Concept Videos

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 specific...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates these...