TY  - JOUR
AU  - Rödel, Franz
AU  - Fleischmann, Maximilian
AU  - Diefenhardt, Markus
AU  - Dapper, Hendrik
AU  - Hoffmann, Annett
AU  - Rödel, Claus
AU  - Martin, Daniel
AU  - Fokas, Emmanouil
TI  - Emerging advances and future opportunities in the molecular and therapeutic landscape of anal cancer.
JO  - Nature reviews / Clinical oncology
VL  - 22
SN  - 1759-4774
CY  - New York, NY
PB  - Nature Publ. Group
M1  - DKFZ-2025-01000
SP  - 483–498
PY  - 2025
N1  -  22, pages 483–498 (2025)
AB  - Anal squamous cell carcinoma (ASCC) is a rare malignancy with an increasing incidence. Primary chemoradiotherapy (CRT) is the standard-of-care treatment for patients with localized ASCC. In the metastatic setting, trials testing immune-checkpoint inhibitor monotherapy have demonstrated outcomes similar to those of patients receiving chemotherapy. Conversely, adding the anti-PD-1 antibody retifanlimab to chemotherapy in patients with recurrent or metastatic ASCC has been shown to significantly improve outcomes. Despite considerable efforts to develop personalized therapy, treatment guidance and prognosis remain reliant on baseline clinical characteristics. An improved understanding of the molecular characteristics of ASCC has provided insights into the mechanisms that mediate tumour progression and response to CRT. For example, human papillomavirus (HPV) infection is known to have an aetiological role in most ASCCs and can modulate cellular responses to CRT via several distinct mechanisms. In this Review, we summarize emerging advances in the molecular and therapeutic landscape of ASCC, including the implementation of biomarkers for treatment guidance and translation into new therapeutic approaches, with HPV infection constituting a global determinant of both tumour biology and clinical outcome. We also discuss the rationale for combining immune-checkpoint inhibitors with CRT in patients with HPV+ tumours.
LB  - PUB:(DE-HGF)16
C6  - pmid:40360682
DO  - DOI:10.1038/s41571-025-01025-x
UR  - https://inrepo02.dkfz.de/record/301328
ER  -