SLX4
Overview
SLX4 (SLX4 structure-specific endonuclease subunit) is a scaffolding protein of the Fanconi anemia (FA) pathway, designated FANCP, that coordinates multiple structure-specific endonucleases to resolve DNA interstrand crosslinks and replication fork intermediates. In cancer genomics, biallelic loss of SLX4 and other FA pathway genes defines a DNA-repair-deficient phenotype associated with platinum sensitivity in prostate cancer.
Alterations observed in the corpus
- FA pathway member; homozygous deleterious events used as a DNA-repair-defect classifier in mCRPC; siRNA knockdown reduced proliferation in prostate cancer cell lines PMID:26928463
Cancer types (linked)
- Metastatic castration-resistant prostate cancer (mCRPC): FA pathway members including SLX4 are homozygously inactivated in a subset of tumors; men with any FA-gene homozygous loss had significantly longer time on carboplatin (P = 0.02) PMID:26928463
Co-occurrence and mutual exclusivity
- Biallelic FA-pathway loss (including SLX4) tends to co-occur with RB1 loss and elevated E2F1 expression in highly proliferative mCRPC PMID:26928463
Therapeutic relevance
- DNA-repair-deficient tumors (homozygous FA-gene loss or ATM inactivation) had significantly longer time on carboplatin (P = 0.02), supporting platinum-based therapy in this biomarker subset PMID:26928463
Open questions
- Prospective validation of FA-pathway loss as a carboplatin-response biomarker in mCRPC is needed before clinical use PMID:26928463
Sources
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