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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer.
|
|---|---|
| Published in |
Clinical Cancer Research, July 2023
|
| DOI | 10.1158/1078-0432.ccr-22-3930 |
| Pubmed ID | |
| Authors |
Harshabad Singh, Rachel B Keller, Kevin S Kapner, Julien Dilly, Srivatsan Raghavan, Chen Yuan, Elizabeth F Cohen, Michael Tolstorukov, Elizabeth Andrews, Lauren K Brais, Annacarolina da Silva, Kimberly Perez, Douglas A Rubinson, Rishi Surana, Marios Giannakis, Kimmie Ng, Thomas E Clancy, Matthew B Yurgelun, Benjamin L Schlechter, Jeffrey W Clark, Geoffrey I Shapiro, Michael H Rosenthal, Jason L Hornick, Valentina Nardi, Yvonne Y Li, Hersh Gupta, Andrew D Cherniack, Matthew Meyerson, James M Cleary, Jonathan A Nowak, Brian M Wolpin, Andrew J Aguirre |
| Abstract |
Approximately 8-10% of pancreatic ductal adenocarcinomas (PDAC) do not harbor mutations in KRAS. Understanding the unique molecular and clinical features of this subset of pancreatic cancer is important to guide patient stratification for clinical trials of molecularly targeted agents. We analyzed a single-institution cohort of 795 exocrine pancreatic cancer cases (including 785 PDAC cases) with a targeted multi-gene sequencing panel and identified 73 patients (9.2%) with KRAS wild-type (WT) pancreatic cancer. Overall, 43.8% (32/73) of KRAS WT cases had evidence of an alternative driver of the mitogen activated kinase (MAPK) pathway, including BRAF mutations and in-frame deletions and receptor-tyrosine kinase (RTK) fusions. Conversely, 56.2% of cases did not harbor a clear MAPK driver alteration, but 29.3% of these MAPK-negative KRAS WT cases (12/41) demonstrated activating alterations in other oncogenic drivers such as GNAS, MYC, PIK3CA and CTNNB1. We demonstrate potent efficacy of pan-RAF and MEK inhibition in patient-derived organoid (PDO) models carrying BRAF in-frame deletions. Moreover, we demonstrate durable clinical benefit of targeted therapy in a patient harboring a KRAS WT tumor with a ROS1fusion. Clinically, patients with KRAS WT tumors were significantly younger in age of onset (Median Age: 62.6 vs. 65.7 years , p = 0.037). SMAD4 mutations were associated with a particularly poor prognosis in KRAS WT cases. This study defines the genomic underpinnings of KRAS WT pancreatic cancer and highlights potential therapeutic avenues for future investigation in molecularly directed clinical trials. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 7 | 9% |
| United Kingdom | 1 | 1% |
| Taiwan | 1 | 1% |
| Unknown | 65 | 88% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 40 | 54% |
| Scientists | 23 | 31% |
| Practitioners (doctors, other healthcare professionals) | 9 | 12% |
| Science communicators (journalists, bloggers, editors) | 2 | 3% |
Mendeley readers
The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 10 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 40% |
| Student > Ph. D. Student | 1 | 10% |
| Student > Master | 1 | 10% |
| Unknown | 4 | 40% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 4 | 40% |
| Medicine and Dentistry | 2 | 20% |
| Agricultural and Biological Sciences | 1 | 10% |
| Unknown | 3 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 39. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 December 2023.
All research outputs
#1,114,885
of 26,386,754 outputs
Outputs from Clinical Cancer Research
#728
of 13,434 outputs
Outputs of similar age
#20,971
of 373,622 outputs
Outputs of similar age from Clinical Cancer Research
#11
of 127 outputs
Altmetric has tracked 26,386,754 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 13,434 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.0. This one has done particularly well, scoring higher than 94% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 373,622 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 94% of its contemporaries.
We're also able to compare this research output to 127 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.