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Retinoid related molecules: new promises against lung and breast cancer
1MAXIA Pharmaceuticals, Inc. and Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, CA 92121, USA.
Abstract:
Retinoids have long interested cancer researchers due to their well-documented antiproliferative and differentiation inducing activities. However, natural compounds such as all-trans and 9-cis retinoic acid, as well as related synthetic derivatives, show only moderate anticancer activities, while at the same time inducing a broad range of undesirable activities. By taking advantage of the newly gained understanding in retinoid action and screening large numbers of novel molecules, new potent anticancer agents have been discovered that often lack typical retinoid side effects. Two of these novel types of molecules, referred to here as retinoid related molecules (RRMs), are described, one of which effectively kills non small cell lung cancer cells by apoptosis and is effective and well tolerated in vivo, while the other one belongs to a class of molecules selective for the nuclear receptor, RXR, which promises to be more effective and more tolerable than presently used compounds in anti-breast cancer adjuvant therapy. These novel molecules demonstrate the potential of novel RRMs that vastly outreaches classical retinoids.
Insights
Novel retinoid-related molecules (RRMs) show potent anticancer activity with fewer side effects than traditional retinoids. These new compounds are effective against non-small cell lung cancer and offer improved breast cancer adjuvant therapy options.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Retinoids exhibit antiproliferative and differentiation-inducing properties relevant to cancer research.
- Classical retinoids like all-trans and 9-cis retinoic acid possess moderate anticancer efficacy and undesirable side effects.
- Understanding retinoid mechanisms has led to the development of novel therapeutic agents.
Purpose of the Study:
- To introduce and describe novel retinoid-related molecules (RRMs) with enhanced anticancer potential.
- To highlight RRMs that overcome the limitations of traditional retinoids, including reduced side effects.
- To present RRMs targeting specific cancer types and therapeutic applications.
Main Methods:
- Screening of novel molecular compounds based on new insights into retinoid action.
- Evaluation of RRMs for their ability to induce apoptosis in cancer cells.
- In vivo testing of RRMs for efficacy and tolerability.
- Characterization of RRMs targeting specific nuclear receptors like RXR.
Main Results:
- Discovery of potent anticancer agents, referred to as RRMs, with reduced typical retinoid side effects.
- One RRM demonstrated effective apoptosis induction in non-small cell lung cancer cells, with good in vivo tolerability.
- Another RRM class selectively targets the RXR nuclear receptor, showing promise for breast cancer adjuvant therapy.
- These novel RRMs exhibit superior potential compared to classical retinoids.
Conclusions:
- Novel retinoid-related molecules (RRMs) represent a significant advancement over traditional retinoids in cancer therapy.
- RRMs offer potent anticancer activity with improved safety profiles, addressing key limitations of existing treatments.
- The development of RRMs targeting specific pathways, like RXR, holds promise for more effective and tolerable cancer treatments.
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