Homologous Recombination Deficiency (HRD) in Cutaneous Oncology

Favour A. Akinjiyan, Renee Morecroft, Jordan Phillipps, Tolulope Adeyelu, Andrew Elliott, Soo J. Park, Omar H. Butt, Alice Y. Zhou, George Ansstas

Research output: Contribution to journalReview articlepeer-review


Skin cancers, including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and melanoma, are the most common malignancies in the United States. Loss of DNA repair pathways in the skin plays a significant role in tumorigenesis. In recent years, targeting DNA repair pathways, particularly homologous recombination deficiency (HRD), has emerged as a potential therapeutic approach in cutaneous malignancies. This review provides an overview of DNA damage and repair pathways, with a focus on HRD, and discusses major advances in targeting these pathways in skin cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors have been developed to exploit HRD in cancer cells. PARP inhibitors disrupt DNA repair mechanisms by inhibiting PARP enzymatic activity, leading to the accumulation of DNA damage and cell death. The concept of synthetic lethality has been demonstrated in HR-deficient cells, such as those with BRCA1/2 mutations, which exhibit increased sensitivity to PARP inhibitors. HRD assessment methods, including genomic scars, RAD51 foci formation, functional assays, and BRCA1/2 mutation analysis, are discussed as tools for identifying patients who may benefit from PARP inhibitor therapy. Furthermore, HRD has been implicated in the response to immunotherapy, and the combination of PARP inhibitors with immunotherapy has shown promising results. The frequency of HRD in melanoma ranges from 18% to 57%, and studies investigating the use of PARP inhibitors as monotherapy in melanoma are limited. Further research is warranted to explore the potential of PARP inhibition in melanoma treatment.

Original languageEnglish
Article number10771
JournalInternational journal of molecular sciences
Issue number13
StatePublished - Jul 2023


  • DNA repair
  • PARP inhibitors
  • genomic scars
  • homologous recombination deficiency
  • immunotherapy
  • melanoma
  • skin cancer
  • synthetic lethality


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