Multidrug resistance in cancer
1Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand. b.baguley@auckland.ac.nz
Methods in Molecular Biology (Clifton, N.J.)
|December 2, 2009
Summary
Human tumour stem cells drive cancer growth and resist treatments through self-renewal and protective mechanisms. Overcoming this resistance, especially host-mediated factors, requires further research for effective cancer therapies.
Area of Science:
- Oncology
- Cell Biology
- Cancer Stem Cell Research
Background:
- Human tumors are driven by a small population of self-renewing tumor stem cells (TSCs).
- TSCs possess inherent resistance mechanisms to genotoxic agents, similar to normal stem cells.
- Understanding TSC resistance is crucial for developing effective cancer treatments.
Purpose of the Study:
- To elucidate the mechanisms by which tumor stem cells resist genotoxic agents.
- To explore both intrinsic cellular properties and microenvironmental factors contributing to TSC resistance.
- To identify strategies for overcoming TSC-mediated drug resistance.
Main Methods:
- Review of intrinsic cellular properties enabling TSC resistance, including cell cycle status, drug transporters (e.g., P-glycoprotein), apoptosis resistance, and limited drug diffusion.
- Analysis of genetic changes in TSCs and their interaction with host immune mechanisms.
- Evaluation of current and potential methods to overcome TSC drug resistance.
Main Results:
- TSCs resist genotoxic agents through mechanisms like quiescence, P-glycoprotein expression, apoptosis evasion, and restricted toxin entry.
- Genetic alterations in TSCs can activate host immune responses, which tumors may suppress.
- Existing methods effectively target intrinsic multidrug resistance, but overcoming host-mediated resistance remains challenging.
Conclusions:
- Tumor stem cells employ multiple intrinsic strategies to resist cancer therapies.
- Host-mediated resistance mechanisms in tumors are a significant barrier to treatment efficacy.
- Further research is essential to develop strategies targeting host-mediated resistance for improved cancer treatment outcomes.
More Related Videos
08:46Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
09:58Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Related Concept Videos
02:56Treatment 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...
02:56Treatment Resistent 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...
02:50Combination 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...
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...
02:57Targeted 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...
There are several types of targeted therapies against specific...
02:57Targeted 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...
There are several types of targeted therapies against specific...
02:49Cancer Therapies
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...