# Cut off the emergency programme cancer cells use to survive treatment

Source: https://onco.cc/ideas/idea-bio1-stress-response-blockade/  
OnCo record `idea-bio1-stress-response-blockade` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: research

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/)

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