Targeting the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Colorectal Cancer

Cancers

Silvia Puglisi¹  Andrea Boutros¹  Stefania Sciallero¹  Fabio Catalano¹  Roberto Borea¹  Valentino Martelli¹  Annalice Gandini¹  Alberto Puccini¹  Malvina Cremante¹ 

[1] Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy;

关键词: DNA damage response;    genetics;    clinical trial;    colorectal cancer;    PARP inhibitors;    precision oncology;   

DOI  :  10.3390/cancers14061388

来源: DOAJ

【 摘 要 】

Major advances have been made in CRC treatment in recent years, especially in molecularly driven therapies and immunotherapy. Despite this, a large number of advanced colorectal cancer patients do not benefit from these treatments and their prognosis remains poor. The landscape of DNA damage response (DDR) alterations is emerging as a novel target for treatment in different cancer types. PARP inhibitors have been approved for the treatment of ovarian, breast, pancreatic, and prostate cancers carrying deleterious BRCA1/2 pathogenic variants or homologous recombination repair (HRR) deficiency (HRD). Recent research reported on the emerging role of HRD in CRC and showed that alterations in these genes, either germline or somatic, are carried by up to 15–20% of CRCs. However, the role of HRD is still widely unknown, and few data about their clinical impact are available, especially in CRC patients. In this review, we report preclinical and clinical data currently available on DDR inhibitors in CRC. We also emphasize the predictive role of DDR mutations in response to platinum-based chemotherapy and the potential clinical role of DDR inhibitors. More preclinical and clinical trials are required to better understand the impact of DDR alterations in CRC patients and the therapeutic opportunities with novel DDR inhibitors.

【 授权许可】

Unknown