Data from <i>RAS/RAF</i> Comutation and <i>ERBB2</i> Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer
DOI:
10.1158/1078-0432.c.7181326.v1
Publication Date:
2024-04-15T07:23:31Z
AUTHORS (42)
ABSTRACT
<div>AbstractPurpose:<p><i>ERBB2</i>-amplified colorectal cancer is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic <i>RAS/RAF</i> alterations are not known.</p>Experimental Design:<p>Dana-Farber and Foundation Medicine Inc. Colorectal cohorts genomic profiling were used to identify <i>ERBB2</i>-amplified cases [Dana-Farber, <i>n</i> = 47/2,729 (1.7%); FMI, 1857/49,839 (3.7%)]. Outcomes patients receiving HER2-directed therapies reported (Dana-Farber, 9; Flatiron Health-Foundation clinicogenomic database, FH-FMI CGDB, 38). Multisite HER2 IHC performed understand intratumoral interlesional heterogeneity. The impact <i>RAS</i> comutations on the effectiveness studied in isogenic cell lines xenografts.</p>Results:<p><i>ERBB2</i> amplifications enriched left-sided cancer. Twenty percent cancers have co-occurring alterations. While WT typically clonal <i>ERBB2</i> amplification, lower level <i>ERRB2</i> higher heterogeneity, discordance. These patterns lead differential responsiveness resistance therapy. resistant trastuzumab-based combinations, such as trastuzumab/tucatinib, but retain sensitivity trastuzumab deruxtecan <i>in vitro</i> murine models. Trastuzumab shows clinical efficacy high-level <i>ERBB2-</i>amplified coaltered cancer.</p>Conclusions:<p>Co-occurring define unique that has increased discordance, combinations. Further examination this previously understudied cohort warranted.</p></div>
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (0)
CITATIONS (0)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....