Compartmentalized cancer drug discovery targeting mitochondrial Hsp90 chaperones

B H Kang1, D C Altieri

  • 1Prostate Cancer Discovery and Development Program, Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Oncogene
|August 4, 2009
PubMed

Insights

Targeting cancer cell signaling pathways within specialized mitochondria offers a novel therapeutic strategy. Identifying heat shock protein-90 (Hsp90) in tumor mitochondria, but not normal tissues, reveals a new approach for cancer drug discovery.

Area of Science:

  • Oncology
  • Cell Biology
  • Drug Discovery

Background:

  • Cancer drug discovery faces challenges with traditional targets.
  • Signaling pathways in cancer cells may be organized in specific subcellular compartments.
  • Compartmentalization offers underexplored therapeutic opportunities.

Purpose of the Study:

  • To explore the potential of targeting cancer signaling pathways within specialized subcellular compartments.
  • To investigate the role of heat shock protein-90 (Hsp90) in tumor mitochondria.
  • To identify novel, subcellularly targeted cancer drug discovery strategies.

Main Methods:

  • Analysis of heat shock protein-90 (Hsp90) localization in tumor cells.
  • Comparison of Hsp90 presence in mitochondria of tumor versus normal tissues.
  • Investigating compartmentalized cell survival networks.

Main Results:

  • Heat shock protein-90 (Hsp90) was identified in mitochondria of tumors.
  • Hsp90 was notably absent in mitochondria of most normal tissues.
  • This compartmentalization suggests a specialized network for tumor cell survival.

Conclusions:

  • Mitochondrial Hsp90 in tumors represents a promising, compartmentalized target.
  • Subcellularly targeted drug discovery offers fresh prospects for cancer therapy.
  • Exploiting compartmentalized networks may overcome challenges in cancer treatment.

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...
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...
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...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
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...