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Updated: Feb 13, 2026

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Activity of HSP90 Inhibiton in a Metastatic Lung Cancer Patient With a Germline BRCA1 Mutation

Susana Cedrés1,2, Enriqueta Felip1,2,3, Cristina Cruz4,2

  • 1Thoracic Tumors Group, Vall d'hebron Institute of Oncology, Barcelona, Spain.

Journal of the National Cancer Institute
|March 13, 2018
PubMed

Insights

Heat shock protein 90 inhibitors (HSP90i) combined with chemotherapy showed exceptional efficacy in a patient with BRCA1-mutated lung cancer. This combination therapy also proved effective in a patient-derived xenograft model, highlighting HSP90i as a potential treatment for BRCA-mutated cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Heat shock proteins (HSPs) are crucial molecular chaperones involved in protein stability and cancer cell survival.
  • HSP90 inhibitors (HSP90i) target multiple pathways but have not yet received regulatory approval.
  • Identifying patient populations who can benefit from HSP90i is critical for therapeutic advancement.

Observation:

  • A patient with lung cancer exhibiting a BRCA1/2 deficiency mutational signature showed an exceptional response to cisplatin/gemcitabine plus HSP90i.
  • This patient has continued HSP90i maintenance therapy for over three years.
  • A patient-derived xenograft (PDX) model from a BRCA1-mutated breast cancer patient demonstrated enhanced efficacy of HSP90i combined with chemotherapy.

Findings:

  • The combination of HSP90i with cisplatin and gemcitabine significantly reduced tumor volume in the BRCA1-mutated PDX model compared to chemotherapy alone.
  • Germline BRCA1 mutation was confirmed in the lung cancer patient.
  • The study reproduced the striking efficacy of HSP90i plus chemotherapy in a preclinical model.

Implications:

  • Therapeutic inhibition of HSP90 shows significant efficacy in BRCA-mutated cancers.
  • This finding suggests a new potential strategy for treating patients with BRCA mutations.
  • Identifying patients with BRCA mutations may help select those most likely to benefit from HSP90 inhibitors.

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