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Ali Mirmiran, Mingyi Chen from Pathologist Connect Commented on a Post
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Now that KRAS G12C mutations and other emerging biomarkers are actively being researched as potential therapeutic targets in NSCLC, how will this inform your approach to diagnostic testing and documentation of results? How do you record test results from diagnosis in the event that they become actionable later in a patient’s journey?

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  • 20 hours 22 min
    I will now add KRAS testing to my reflex tests for metastatic NSCLC. All of the results of reflux tests are entered into our EMR (Cerner) for easy access to Show More
  • from Pathologist Connect 22 hours 30 min
    The in house test result will be automatically shown in EMR, the outside report lacks interface, but will be scanned as an addendum of pathology report.
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Sensitive Detection of KRAS Mutations by Clustered Regularly Interspaced Short Palindromic Repeats

Kirsten rat sarcoma viral oncogene (KRAS) is the isoform most frequently mutated in human tumors. Testing for activating KRAS mutations has important implications for diagnosis and the personalized medicine of ..... see more

Source : https://www.mdpi.com/2075-4418/11/1/125/htm

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Distribution of KRASG12C Somatic Mutations across Race, Sex, and Cancer Type

Our apologies. An error occurred while setting your user cookie. Please set your browser to accept cookies to continue. NEJM.org uses cookies to improve performance by remembering your session ID ..... see more

Source : https://www.nejm.org/doi/full/10.1056/NEJMc2030638

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MEK inhibitors for the treatment of non-small cell lung cancer

BRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations in both KRAS and BRAF genes have been identified in non-small cell lung cancer (NSCLC). They ..... see more

Source : https://link.springer.com/article/10.1186/s13045-020-01025-7

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WIDOCK: a reactive docking protocol for virtual screening of covalent inhibitors

Here we present WIDOCK, a virtual screening protocol that supports the selection of diverse electrophiles as covalent inhibitors by incorporating ligand reactivity towards cysteine residues into AutoDock4. WIDOCK applies the ..... see more

Source : https://link.springer.com/article/10.1007/s10822-020-00371-5

Maureen Boardman from Generation NP, Prabhsimranjot Singh Commented on a Post
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A 64-year-old female patient, light current smoker was diagnosed in November 2019 with a cT2aN2M1c lung adenocarcinoma (EGFR wild-type, ALK/ROS1-, HER2-, PD-L1 < 1% by molecular assay). However, molecular testing via NGS panel sequencing revealed a KRAS p.G12C mutation.

Patient was started on pembrolizumab, pemetrexed, and carboplatin in December 2019. In March 2019, the patient began pemetrexed maintenance therapy, which was successfully completed. However, in late December 2020, metastases in the lung, adrenal gland, and brain were found during a routine follow-up scan. The patient has since received successful Gamma Knife surgery for the brain lesions. Repeat molecular testing has confirmed the presence of a KRAS p.G12C mutation. The patient has an ECOG PS
of 1.

What treatment(s) would you recommend for this patient? What factors would you consider when deciding how to treat this patient?

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  • from Generation NP 2 days 4 hours
    As per above I would try to enroll in a clinical trial for KRASG12C and if not eligible consider Sotorasib and if that is not possible Ramucirumab
  • 2 days 7 hours
    I would evaluate to enroll in a clinical trial for KRASG12C and if not eligible or available then try to obtain Sotorasib. If that’s also not available then traditional chemotherapy Show More
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Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries

Current methods used for measuring amino acid side-chain reactivity lack the throughput needed to screen large chemical libraries for interactions across the proteome. Here we redesigned the workflow for activity-based ..... see more

Source : https://www.nature.com/articles/s41587-020-00778-3

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FDA Grants Breakthrough Therapy Designation to Sotorasib for NSCLC with KRAS G12C Mutation

The FDA has granted breakthrough therapy designation to the investigational KRASG12C inhibitor, sotorasib, for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with KRAS ..... see more

Source : https://www.cancernetwork.com/view/fda-grants-breakthrough-therapy-designation-to-sotorasib-for-nsclc-with-kras-g12c-mutation

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  • 4 days 23 hours
    Excited about this and fingers crossed!
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Mechanisms of Resistance to KRASG12C Inhibitors

KRAS is a gene that is commonly mutated in cancer, especially in pancreatic, lung and colorectal cancers. Despite its importance, scientists have for many years been unable to create a ..... see more

Source : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795113/

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  • 5 days
    Great Review but wait for our review in Cancer Discovery!
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Computational Biological Modeling Identifies PD-(L)1 Immunotherapy Sensitivity Among Molecular Subgroups of KRAS -Mutated Non-Small-Cell Lung Cancer

PURPOSE KRAS-mutated (KRASMUT) non-small-cell lung cancer (NSCLC) is emerging as a heterogeneous disease defined by comutations, which may confer differential benefit to PD-(L)1 immunotherapy. In this study, we leveraged computational ..... see more

Source : https://ascopubs.org/doi/abs/10.1200/PO.20.00172

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  • 5 days
    Fascinating! but confirms that data from Dr. F. Skoulidis group