Overcoming Cancer Drug Resistance Utilizing PROTAC Technology
Matthew R Burke1, Alexis R Smith1, Guangrong Zheng1
1Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, United States.
Frontiers in Cell and Developmental Biology
|May 13, 2022
Summary
Proteolysis-targeting chimeras (PROTACs) offer a promising new approach to combat cancer drug resistance. These novel therapeutics can overcome resistance mechanisms and degrade mutated targets, providing new hope for patients.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Cancer drug resistance is a significant obstacle in treating malignancies, often arising from mutated or overexpressed protein targets.
- Traditional targeted therapies frequently lose efficacy due to acquired resistance mechanisms.
Purpose of the Study:
- To review the recent developments in proteolysis-targeting chimeras (PROTACs) for overcoming cancer drug resistance.
- To analyze PROTACs targeting mechanisms that confer resistance to existing cancer therapies.
Main Methods:
- Literature review of recent studies on PROTACs in cancer therapy.
- Analysis of PROTAC development against known cancer targets and resistance mechanisms.
Main Results:
- PROTACs leverage the ubiquitin-proteasome system for targeted protein degradation.
- PROTACs have demonstrated potential in overcoming established resistance mechanisms to conventional targeted therapies.
- Emerging research shows PROTACs can degrade mutated targets responsible for treatment resistance.
Conclusions:
- PROTACs represent a promising therapeutic strategy to address challenges posed by cancer drug resistance.
- Further development of PROTACs offers new avenues for treating previously intractable malignancies.
Keywords:
E3 ubiquitin ligaseacquired resistancecancer drug resistancedrug discoveryproteolysis targeting chimeratargeted protein degradationtargeted therapyMore Related Videos
08:46Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
10.7K
06:44Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
13.5K
Related Concept Videos
02:56Treatment Resistant Cancers
3.4K
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...
3.4K
02:50Combination Therapies and Personalized Medicine
5.1K
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...
5.1K
02:57Targeted Cancer Therapies
7.9K
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...
There are several types of targeted therapies against...
7.9K
02:49Cancer Therapies
8.0K
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...
8.0K
01:27Tumor Immunotherapy
681
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
681
02:53Adaptive Mechanisms in Cancer Cells
6.0K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.0K