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Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Combinatorial application of nucleic acid-based agents targeting protein kinases for cancer treatment
1Department of Obstetrics and Gynecology, Medical School, J.W. Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Birgit.Spaenkuch@t-online.de
Abstract:
The progress made in cancer biology, genetics and biotechnology has led to a major transition in cancer drug design and development, from an emphasis on non-specific, cytotoxic agents to specific, molecular-targeted smart cancer drugs. Many of these targeted agents have shown to have improved selectivity for cancer versus normal cells and are associated with better anti-tumor efficacy and lower toxicity. The new generation of anti-cancer drugs requires low concentrations and minimizes unwanted side effects. Their use leads to enhanced anti-cancer effects and to a reduction of chemotherapy resistance. Still, resistance to common chemotherapeutic agents is a major obstacle in cancer treatment. Silencing of cancer-relevant genes is a challenging strategy to reduce resistance and to sensitize cancer cells towards anti-neoplastic agents. Resistance can be an intrinsic problem of the tumor or can be acquired during the life time of the tumor. A fascinating species of anti-cancer drugs include antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) which are able to specifically down-regulate the expression of the target genes. The combination of nucleic acid-based agents with anti-neoplastic drugs can induce synergistic induction of cell cycle arrest, apoptosis and reduced cell proliferation in vitro or tumor growth in vivo. These two strategies (ASOs and siRNAs) will help to improve current therapeutic regimens. In addition, the combination of targeted drugs with common chemotherapeutic agents might be able to make resistant cells again sensitive towards a chemotherapeutic agent.
Insights
Molecular-targeted cancer drugs offer improved efficacy and reduced toxicity. Combining these with gene silencing strategies like antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) can overcome chemotherapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Cancer drug development has shifted from non-specific cytotoxic agents to specific molecular-targeted therapies.
- Targeted agents demonstrate improved cancer cell selectivity, enhanced anti-tumor efficacy, and reduced toxicity compared to traditional chemotherapy.
- Chemotherapy resistance remains a significant challenge in cancer treatment, necessitating novel therapeutic strategies.
Purpose of the Study:
- To explore the potential of gene silencing using antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to overcome cancer drug resistance.
- To evaluate the synergistic effects of combining nucleic acid-based agents with anti-neoplastic drugs for improved cancer therapy.
- To investigate strategies for sensitizing resistant cancer cells to conventional chemotherapeutic agents.
Main Methods:
- Utilizing antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to specifically down-regulate the expression of cancer-relevant genes.
- Investigating the combination of nucleic acid-based agents with existing anti-neoplastic drugs.
- Assessing the impact of these combined strategies on cell cycle arrest, apoptosis, cell proliferation, and tumor growth in vitro and in vivo.
Main Results:
- Gene silencing via ASOs and siRNAs presents a promising strategy to reduce cancer cell resistance.
- Combination therapies involving nucleic acid agents and anti-neoplastic drugs can induce synergistic anti-cancer effects.
- These combined approaches show potential for enhancing therapeutic regimens and re-sensitizing resistant cancer cells.
Conclusions:
- The development of molecular-targeted cancer drugs represents a significant advancement in oncology.
- Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) offer targeted gene silencing capabilities to combat chemotherapy resistance.
- Combination strategies hold promise for improving current cancer treatment protocols and overcoming drug resistance.
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