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Published on: September 8, 2017
Adaptive mechanisms of resistance to anti-neoplastic agents
Bibiana I Ferreira1,2, Maria K Lie3,4, Agnete S T Engelsen3
1Centre for Biomedical Research (CBMR) , University of Algarve , Campus of Gambelas, Building 8, room 2.22 , 8005-139 Faro , Portugal.
Abstract:
Intrinsic and acquired resistance to conventional and targeted therapeutics is a fundamental reason for treatment failure in many cancer patients. Targeted approaches to overcome chemoresistance as well as resistance to targeted approaches require in depth understanding of the underlying molecular mechanisms. The anti-cancer activity of a drug can be limited by a broad variety of molecular events at different levels of drug action in a cell-autonomous and non-cell-autonomous manner. This review summarizes recent insights into the adaptive mechanisms used by tumours to resist therapy including cellular phenotypic plasticity, dynamic alterations of the tumour microenvironment, activation of redundant signal transduction pathways, modulation of drug target expression levels, and exploitation of pro-survival responses.
Insights
Tumors develop resistance to cancer therapies through adaptive mechanisms like cellular plasticity and microenvironment changes. Understanding these molecular processes is key to overcoming treatment failure.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Therapeutic resistance limits conventional and targeted cancer treatment efficacy.
- Understanding resistance mechanisms is crucial for developing effective cancer therapies.
- Drug action can be hindered by cell-autonomous and non-cell-autonomous molecular events.
Purpose of the Study:
- To review recent insights into tumor adaptive resistance mechanisms.
- To highlight molecular strategies tumors employ to evade therapy.
- To provide a foundation for overcoming therapeutic resistance.
Main Methods:
- Literature review of recent studies on cancer therapy resistance.
- Synthesis of findings on molecular and cellular adaptive mechanisms.
- Analysis of tumor microenvironment and signaling pathway alterations.
Main Results:
- Tumors exhibit adaptive resistance via phenotypic plasticity.
- Dynamic tumor microenvironment alterations contribute to resistance.
- Redundant signaling pathways and altered drug target levels are key mechanisms.
- Exploitation of pro-survival responses enhances tumor resilience.
Conclusions:
- Adaptive resistance is a complex, multi-faceted challenge in cancer therapy.
- Targeted strategies must address diverse resistance mechanisms.
- Further research into these adaptive strategies is essential for improving patient outcomes.
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