OnCo
ideasIdea

Cut off the emergency programme cancer cells use to survive treatment

When attacked, cells switch on a survival programme that buys them time to adapt. Blocking that programme could turn a partial response into a complete one.

The integrated stress response, heat shock factor 1 activity and autophagy are rapidly induced after targeted therapy and support survival during the adaptation window. Inhibitors of eIF2B-mediated stress signalling, HSF1 and autophagy exist at various stages of development. The proposal is combination timed to the adaptation window (the first days after therapy initiation) rather than continuous co-dosing.

Hypothesis
Blocking the acute stress response during the first days of targeted therapy increases the depth of response, measured by residual tumour cell number or ctDNA nadir, compared with the targeted agent alone.
Rationale
Adaptation precedes mutation; models consistently show a survival advantage from stress-response activation, and the window is short so exposure and toxicity can be limited.
What would test it
Preclinical combination studies with ctDNA-equivalent depth-of-response readouts, followed by a window-of-opportunity clinical study measuring residual disease at two weeks.
Maturity
preclinical evidence
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
6
Bottlenecks it attacks

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