Reference Detail

Ref Type

Journal Article

PMID

(37255276)

Authors

Hunt AL, Nutcharoen A, Randall J, Papazian A, Deeken J, Maxwell GL, Bateman NW, Petricoin EF, Benyounes A, Conrads TP, Cannon TL

Title

Integration of Multi-omic Data in a Molecular Tumor Board Reveals EGFR-Associated ALK-Inhibitor Resistance in a Patient With Inflammatory Myofibroblastic Cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
The oncologist	28	8	2023 Aug 03	730-736	Oncologist

URL

Abstract Text

Inflammatory myofibroblastic tumors (IMTs) are intermediate-grade mesenchymal neoplasms commonly characterized by chromosomal rearrangements causing constitutive activation of anaplastic lymphoma kinase (ALK) and/or ALK mutations causing reduced sensitivity to ALK tyrosine kinase inhibitors (TKI). We present a patient with an IMT who initially responded to first-line alectinib, but who later suffered disease relapse and presently survives with moderate residual disease after receiving second-line lorlatinib. Biopsy specimens were analyzed using next generation sequencing (DNA-seq and RNA-seq) and reverse phase protein microarray (RPPA) as part of an institutional Molecular Tumor Board (MTB) study. An EML4-ALK rearrangement and EGFR activation (pEGFRY1068) were present in both the primary and recurrent tumors, while a secondary ALK I1171N mutation was exclusive to the latter. EGFR signaling in the background of a secondary ALK mutation is correlated with reduced ALK TKI sensitivity in vitro, implicating an important mechanism of drug resistance development in this patient. The RPPA results also critically demonstrate that ALK signaling (ALKY1604) was not activated in the recurrent tumor, thereby indicating that standard-of-care use of third- or fourth-line ALK TKI would not likely be efficacious or durable. These results underscore the importance of real-time clinical integration of functional protein drug target activation data with NGS in the MTB setting for improving selection of patient-tailored therapy.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK ALK I1171N	inflammatory myofibroblastic tumor	predicted - resistant	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, ALK I1171N was identified on post-progression biopsy in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK, who previously responded to Alecensa (alectinib) (PMID: 37255276).	37255276
EML4 - ALK ALK I1171N	inflammatory myofibroblastic tumor	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, Lorbrena (lorlatinib) treatment resulted in near resolution of the pleural effusion and decrease in pleural mass in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK and ALK I1171N (PMID: 37255276).	37255276
EML4 - ALK	inflammatory myofibroblastic tumor	predicted - sensitive	Alectinib	Case Reports/Case Series	Actionable	In a clinical case study, Alecensa (alectinib) treatment resulted in a near-complete radiographic response after 3 months in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK (PMID: 37255276).	37255276