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Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

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Centralized Homologous Recombination Repair Testing in Metastatic Castration-Resistant Prostate Cancer: Real-World

Belén Caramelo1,2, Pilar García-Berbel2,3, Sofia Del Carmen2,3

  • 1Medical Oncology Department, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain.

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|May 27, 2026
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Summary

Centralized homologous recombination repair (HRR) testing in metastatic castration-resistant prostate cancer (mCRPC) is feasible and efficient in Spain. This strategy identified actionable HRR alterations in 18% of patients, supporting precision medicine.

Keywords:
BRCAPARP inhibitorhomologous recombination repairprostate cancer

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Diagnostics

Background:

  • Homologous recombination repair (HRR) status is critical for targeted therapy selection in metastatic castration-resistant prostate cancer (mCRPC).
  • Variability in HRR testing access and performance necessitates standardized approaches.
  • A centralized testing strategy was evaluated for mCRPC patients in Spain.

Purpose of the Study:

  • To assess the feasibility, efficiency, and outcomes of a centralized HRR testing strategy for mCRPC patients.
  • To determine the prevalence of HRR gene alterations in this population.
  • To evaluate the impact on precision medicine initiatives.

Main Methods:

  • A standardized 38-gene next-generation sequencing (NGS) assay was used for analysis.
  • 1412 formalin-fixed paraffin-embedded (FFPE) tumor samples from mCRPC patients across 89 Spanish institutions were analyzed.
  • Five key HRR genes (BRCA1, BRCA2, CHEK2, ATM, CDK12) were included in the assay.

Main Results:

  • Pathogenic or likely pathogenic HRR alterations were found in 18% of mCRPC patients.
  • BRCA2 (6%) was the most frequent alteration, followed by ATM (5%), CDK12 (4%), BRCA1 (2%), and CHEK2 (1%).
  • The average turnaround time was 18 days, with a sample rejection rate of 13% and a failure rate of 2%.

Conclusions:

  • Centralized HRR testing in mCRPC patients in Spain is feasible, efficient, and reliable.
  • The 18% detection rate of pathogenic alterations aligns with existing literature.
  • This approach enhances precision medicine by improving the identification of actionable HRR alterations.