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Playing cancer at its own game: activating mitogenic signaling as a paradoxical intervention
Matheus Henrique Dias1, René Bernards1
1Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract:
In psychotherapy, paradoxical interventions are characterized by a deliberate reinforcement of the pathological behavior to improve the clinical condition. Such a counter-intuitive approach can be considered when more conventional interventions fail. The development of targeted cancer therapies has enabled the selective inhibition of activated oncogenic signaling pathways. However, in advanced cancers, such therapies, on average, deliver modest benefits due to the development of resistance. Here, we review the perspective of a 'paradoxical intervention' in cancer therapy: rather than attempting to inhibit oncogenic signaling, the proposed therapy would further activate mitogenic signaling to disrupt the labile homeostasis of cancer cells and overload stress response pathways. Such overactivation can potentially be combined with stress-targeted drugs to kill overstressed cancer cells. Although counter-intuitive, such an approach exploits intrinsic and ubiquitous differences between normal and cancer cells. We discuss the background underlying this unconventional approach and how such intervention might address some current challenges in cancer therapy.
Insights
This study proposes a paradoxical cancer therapy approach. Instead of inhibiting cancer growth, it suggests activating signaling pathways to overload cancer cells, potentially leading to their death.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Conventional cancer therapies face challenges with resistance and modest benefits in advanced stages.
- Paradoxical interventions in psychotherapy reinforce pathological behaviors to improve conditions.
- Targeted cancer therapies inhibit oncogenic signaling but often encounter resistance.
Purpose of the Study:
- To explore a 'paradoxical intervention' strategy for cancer therapy.
- To propose activating mitogenic signaling rather than inhibiting it.
- To discuss how this approach could overcome current cancer treatment challenges.
Main Methods:
- Reviewing the concept of paradoxical interventions.
- Analyzing the potential of overactivating mitogenic signaling in cancer cells.
- Considering combination therapy with stress-targeted drugs.
Main Results:
- The proposed therapy aims to disrupt cancer cell homeostasis and overload stress response pathways.
- Overactivation of signaling could lead to cancer cell death.
- This approach leverages differences between normal and cancer cells.
Conclusions:
- A paradoxical approach of activating oncogenic signaling offers a novel strategy for cancer therapy.
- This unconventional method may provide a new avenue to combat advanced cancers and resistance.
- Further research is needed to explore the clinical applicability of paradoxical cancer interventions.
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