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The Role of HSF1 in Tumor Adaptation to Proteotoxic Stress: Synthetic Lethality and Targeted Inhibition Strategies

Public support

  • Provider

    Czech Science Foundation

  • Programme

    Standard projects

  • Call for proposals

    SGA0202600001

  • Main participants

    Masarykův onkologický ústav

  • Contest type

    VS - Public tender

  • Contract ID

    26-21679S

Alternative language

  • Project name in Czech

    The Role of HSF1 in Tumor Adaptation to Proteotoxic Stress: Synthetic Lethality and Targeted Inhibition Strategies

  • Annotation in Czech

    Cancer cells depend on proteostasis to survive increased protein synthesis and proteotoxic stress, making proteostasis pathways attractive therapeutic targets. The transcription factor HSF1 is a key regulator of this response, promoting chaperone expression and adaptation to stress. In tumors, HSF1 is often constitutively active and supports malignant progression, yet the mechanisms controlling its function remain poorly defined. This project will investigate how HSF1 is reprogrammed in cancer, focusing on understudied regulatory layers such as SUMOylation, liquid-liquid phase separation, and protein stability. This project aims to elucidate how HSF1 is functionally reprogrammed in cancer cells and to uncover novel regulatory mechanisms that create therapeutic vulnerabilities. By providing fundamental insights into the molecular control of HSF1 activity in oncogenesis, this research will inform the development of innovative therapeutic strategies aimed at disrupting tumor-specific proteostasis networks.

Scientific branches

  • R&D category

    ZV - Basic research

  • OECD FORD - main branch

    30204 - Oncology

  • OECD FORD - secondary branch

    10601 - Cell biology

  • OECD FORD - another secondary branch

    10608 - Biochemistry and molecular biology

  • CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)

    CE - Biochemistry<br>EA - Morphology and cytology<br>EB - Genetics and molecular biology<br>FD - Oncology and haematology

Solution timeline

  • Realization period - beginning

    Jan 1, 2026

  • Realization period - end

    Dec 31, 2028

  • Project status

    Z - Beginning multi-year project

  • Latest support payment

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP26-GA0-GA-R

  • Data delivery date

    May 6, 2026

Finance

  • Total approved costs

    9,622 thou. CZK

  • Public financial support

    9,523 thou. CZK

  • Other public sources

    99 thou. CZK

  • Non public and foreign sources

    0 thou. CZK