Related Experiment Video
Updated: Aug 23, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Fuzzy optimization for identifying anti-cancer targets with few side effects in constraint-based models of head and
Feng-Sheng Wang1, Pei-Rong Chen1, Ting-Yu Chen1
1Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan.
Abstract:
Computer-aided methods can be used to screen potential candidate targets and to reduce the time and cost of drug development. In most of these methods, synthetic lethality is used as a therapeutic criterion to identify drug targets. However, these methods do not consider the side effects during the identification stage. This study developed a fuzzy multi-objective optimization for identifying anti-cancer targets that not only evaluated cancer cell mortality, but also minimized side effects due to treatment. We identified potential anti-cancer enzymes and antimetabolites for the treatment of head and neck cancer (HNC). The identified one- and two-target enzymes were primarily involved in six major pathways, namely, purine and pyrimidine metabolism and the pentose phosphate pathway. Most of the identified targets can be regulated by approved drugs; thus, these drugs are potential candidates for drug repurposing as a treatment for HNC. Furthermore, we identified antimetabolites involved in pathways similar to those identified using a gene-centric approach. Moreover, HMGCR knockdown could not block the growth of HNC cells. However, the two-target combinations of (UMPS, HMGCR) and (CAD, HMGCR) could achieve cell mortality and improve metabolic deviation grades over 22% without reducing the cell viability grade.
Insights
This study introduces a novel fuzzy optimization method to identify anti-cancer drug targets for head and neck cancer (HNC). The approach minimizes side effects while maximizing cancer cell death, identifying promising targets for drug repurposing.
Area of Science:
- Oncology
- Computational Biology
- Pharmacology
Background:
- Computer-aided drug discovery often uses synthetic lethality but overlooks treatment side effects.
- Identifying effective anti-cancer targets requires balancing efficacy with safety profiles.
Purpose of the Study:
- To develop a fuzzy multi-objective optimization method for identifying anti-cancer targets.
- To evaluate cancer cell mortality and minimize treatment-related side effects for head and neck cancer (HNC).
Main Methods:
- Utilized fuzzy multi-objective optimization to screen potential anti-cancer enzymes and antimetabolites.
- Focused on pathways including purine/pyrimidine metabolism and the pentose phosphate pathway.
- Investigated single and dual-target enzyme combinations, including HMGCR, UMPS, and CAD.
Main Results:
- Identified key enzymes and antimetabolites involved in critical cancer metabolic pathways.
- Found that most identified targets are druggable with existing medications, suggesting drug repurposing potential for HNC.
- Demonstrated that dual-target combinations (UMPS, HMGCR) and (CAD, HMGCR) significantly improved metabolic deviation and induced cell mortality without compromising cell viability.
Conclusions:
- The developed fuzzy optimization approach effectively identifies anti-cancer targets by considering both efficacy and safety.
- Identified specific enzyme targets and antimetabolites for HNC treatment, with potential for drug repurposing.
- Dual-target strategies show promise for enhanced therapeutic outcomes in HNC by improving metabolic control and reducing viability.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:50Combination Therapies and Personalized Medicine
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...
02:26Protein Networks
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...