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Retinoid targets for the treatment of cancer
Zivjena Buletic1, Kenneth J Soprano, Dianne Robert Soprano
1Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Abstract:
Retinoic acid (RA), the most potent natural retinoid, is essential for normal cell growth and differentiation. The RA signaling pathway is multistep, involving the precise regulation of retinoid levels and the control of RA-dependent gene expression in target cells. Within this complex scheme, there are many different aberrations in the RA signaling pathway of tumor cells that have been found to be associated with abnormal cell growth and tumorigenesis. This article reviews the normal pathways of RA signaling, followed by a discussion of the various sites that have been implicated in tumorigenesis and targeted for drug development. Currently, there are several retinoids and one rexinoid approved for the treatment of specific cancers. Future experimentation in drug discovery will continue to explore the efficacy of retinoids/rexinoids, either alone or in combination with other chemotherapeutic agents and/or chromatin remodeling agents, and the development of agents to modulate RA metabolism within cells. It is likely that different drug treatments will be developed that are specifically tailored to the unique point(s) in the RA signaling pathways that are aberrant in specific types of tumor cells.
Insights
Retinoic acid (RA) signaling is crucial for cell growth. Aberrations in this pathway are linked to cancer, prompting research into targeted retinoid therapies for tumor treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Retinoic acid (RA) is a potent retinoid vital for normal cell growth and differentiation.
- The RA signaling pathway involves complex regulation of retinoid levels and gene expression.
- Aberrations in the RA pathway are implicated in tumor cell growth and tumorigenesis.
Purpose of the Study:
- To review normal RA signaling pathways.
- To discuss tumorigenesis sites linked to RA signaling.
- To explore drug development targets within the RA pathway.
Main Methods:
- Literature review of RA signaling pathways.
- Analysis of implicated sites in tumorigenesis.
- Discussion of current and future drug development strategies.
Main Results:
- Abnormalities in RA signaling are associated with cancer development.
- Several retinoids and one rexinoid are approved for cancer treatment.
- Ongoing research focuses on combination therapies and modulating RA metabolism.
Conclusions:
- Targeted drug development for aberrant RA signaling in specific tumors is promising.
- Future treatments may involve retinoids/rexinoids alone or with other agents.
- Personalized medicine approaches tailoring treatments to specific pathway defects are likely.
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