Molecular Characterization and Therapeutic Opportunities in KRAS Wildtype Pancreatic Ductal Adenocarcinoma Article Swipe
Aakash Desai
,
Alexander Xiao
,
Daheui Choi
,
Merih Deniz Toruner
,
Daniel Walden
,
Þorvarður R. Hálfdánarson
,
Steven R. Alberts
,
Robert R. McWilliams
,
Amit Mahipal
,
Daniel H. Ahn
,
Hani M. Babiker
,
Gulnaz Stybayeva
,
Alexander Revzin
,
Sani H. Kizilbash
,
Alex A. Adjei
,
Tanios Bekaii‐Saab
,
Aaron S. Mansfield
,
Ryan M. Carr
,
Wen Wee
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3390/cancers16101861
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.3390/cancers16101861
Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics.
Related Topics
Concepts
KRAS
Crizotinib
Medicine
Cancer research
Oncology
STK11
Internal medicine
Clinical trial
Transcriptome
Bioinformatics
Biology
Gene
Cancer
Gene expression
Genetics
Lung cancer
Colorectal cancer
Malignant pleural effusion
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cancers16101861
- https://www.mdpi.com/2072-6694/16/10/1861/pdf?version=1715601832
- OA Status
- gold
- Cited By
- 2
- References
- 36
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4396870635
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4396870635Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/cancers16101861Digital Object Identifier
- Title
-
Molecular Characterization and Therapeutic Opportunities in KRAS Wildtype Pancreatic Ductal AdenocarcinomaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-05-13Full publication date if available
- Authors
-
Aakash Desai, Alexander Xiao, Daheui Choi, Merih Deniz Toruner, Daniel Walden, Þorvarður R. Hálfdánarson, Steven R. Alberts, Robert R. McWilliams, Amit Mahipal, Daniel H. Ahn, Hani M. Babiker, Gulnaz Stybayeva, Alexander Revzin, Sani H. Kizilbash, Alex A. Adjei, Tanios Bekaii‐Saab, Aaron S. Mansfield, Ryan M. Carr, Wen WeeList of authors in order
- Landing page
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https://doi.org/10.3390/cancers16101861Publisher landing page
- PDF URL
-
https://www.mdpi.com/2072-6694/16/10/1861/pdf?version=1715601832Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.mdpi.com/2072-6694/16/10/1861/pdf?version=1715601832Direct OA link when available
- Concepts
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KRAS, Crizotinib, Medicine, Cancer research, Oncology, STK11, Internal medicine, Clinical trial, Transcriptome, Bioinformatics, Biology, Gene, Cancer, Gene expression, Genetics, Lung cancer, Colorectal cancer, Malignant pleural effusionTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2Per-year citation counts (last 5 years)
- References (count)
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36Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W3146983201, https://openalex.org/W2151253787, https://openalex.org/W4251110191, https://openalex.org/W1985720035, https://openalex.org/W3138007187, https://openalex.org/W4392639138, https://openalex.org/W3003574401, https://openalex.org/W2793938850, https://openalex.org/W2984359187, https://openalex.org/W3080980743, https://openalex.org/W2119345781, https://openalex.org/W3008479902, https://openalex.org/W2919944461, https://openalex.org/W2285093314, https://openalex.org/W4220775305, https://openalex.org/W2944381634, https://openalex.org/W2130410032, https://openalex.org/W4306708184, https://openalex.org/W1550536217, https://openalex.org/W6785331024, https://openalex.org/W3008107700, https://openalex.org/W3035138898, https://openalex.org/W2214074259, https://openalex.org/W2905272879, https://openalex.org/W3095252657, https://openalex.org/W3203777534, https://openalex.org/W2807073218, https://openalex.org/W3009738007, https://openalex.org/W2789416018, https://openalex.org/W2959096163, https://openalex.org/W2768082354, https://openalex.org/W6678047426, https://openalex.org/W2803358834, https://openalex.org/W4221005208, https://openalex.org/W3102437379, https://openalex.org/W4226456471 |
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