Biomarkers /
KRAS Q61E
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Overview
KRAS Q61E is present in 0.00% of AACR GENIE cases, with colorectal adenocarcinoma having the greatest prevalence [4].
Biomarker-Directed Therapies
KRAS Q61E is a predictive biomarker for use of afatinib, dacomitinib, erlotinib, gefitinib, osimertinib, cetuximab, and panitumumab in patients.
There are 2 FDA approvals and 7 NCCN guidelines that support the use of a targeted therapy based on the presence of KRAS Q61E.
Non-small cell lung carcinoma and colorectal carcinoma have the most therapies targeted against KRAS Q61E or its related pathways [5].
Afatinib +
Non-Small Cell Lung Carcinoma -
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Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Cetuximab +
Dacomitinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN, MCG) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Erlotinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN, MCG) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Gefitinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Osimertinib +
Non-Small Cell Lung Carcinoma -
|
Biomarker Criteria:
Sample must match one or more of the following:
|
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN, MCG) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
|
Biomarker Criteria:
Sample must match all of the following:
Sample must match one or more of the following: Sample must match one or more of the following: |
Predicted Response: Primary Resistance |
| Clinical Setting(s): Metastatic (NCCN) | |
| Note: According to NCCN, mutations in KRAS have been associated with reduced responsiveness to EGFR TKI therapy. |
Clinical Trials
KRAS Q61E serves as an inclusion eligibility criterion in 6 clinical trials, of which 4 are open and 2 are closed. Of the trials that contain KRAS Q61E as an inclusion criterion, 4 are phase 1 (3 open) and 2 are phase 2 (1 open).
Trials with KRAS Q61E in the inclusion eligibility criteria most commonly target acute myeloid leukemia, cancer, non-small cell lung carcinoma, rectal carcinoma, and thyroid gland adenocarcinoma [5].
Trametinib, akt inhibitor gsk2141795, iodine i-124 fiau, binimetinib, and carboplatin are the most frequent therapies in trials with KRAS Q61E as an inclusion criteria [5].
Significance of KRAS Q61E in Diseases
Acute Myeloid Leukemia +
KRAS is mutated in 3.77% of acute myeloid leukemia patients [4].
KRAS Q61E is an inclusion criterion in 2 clinical trials for acute myeloid leukemia, of which 0 are open and 2 are closed. Of the trials that contain KRAS Q61E and acute myeloid leukemia as inclusion criteria, 1 is phase 1 (0 open) and 1 is phase 2 (0 open) [5].
Akt inhibitor gsk2141795, binimetinib, and cytarabine are the most frequent therapies in trials for acute myeloid leukemia that contain KRAS Q61E [5].
Rectal Carcinoma +
KRAS is mutated in 41.92% of rectal carcinoma patients with KRAS Q61E present in 0.11% of all rectal carcinoma patients [4].
KRAS Q61E is an inclusion criterion in 1 clinical trial for rectal carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS Q61E and rectal carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
Non-Small Cell Lung Carcinoma +
KRAS is mutated in 29.7% of non-small cell lung carcinoma patients [4].
KRAS Q61E is an inclusion criterion in 1 clinical trial for non-small cell lung carcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS Q61E and non-small cell lung carcinoma as inclusion criteria, 1 is phase 1 (1 open) [5].
Carboplatin, paclitaxel, and trametinib are the most frequent therapies in trials for non-small cell lung carcinoma that contain KRAS Q61E [5].
Thyroid Gland Adenocarcinoma +
KRAS is mutated in 4.07% of thyroid gland adenocarcinoma patients [4].
KRAS Q61E is an inclusion criterion in 1 clinical trial for thyroid gland adenocarcinoma, of which 1 is open and 0 are closed. Of the trial that contains KRAS Q61E and thyroid gland adenocarcinoma as inclusion criteria, 1 is phase 2 (1 open) [5].
Iodine i-124 fiau, iodine i-131, and trametinib are the most frequent therapies in trials for thyroid gland adenocarcinoma that contain KRAS Q61E [5].
References
1. Hart R and Prlic A. Universal Transcript Archive Repository. Version uta_20170629. San Francisco CA: Github;2015. https://github.com/biocommons/uta
2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.
3. Liu X, Wu C, Li C, and Boerwinkle E. dbNSFP v3.0: A one-stop database of functional predictions and annotations for human nonsynonymous and splice site SNVs. Human Mutation. 2015;37:235-241.
Liu X, Jian X, and Boerwinkle E. dbNSFP: A lightweight database of human nonsynonymous SNPs and their functional predictions. Human Mutation. 2011;32:894-899.
4. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 4. This dataset does not represent the totality of the genetic landscape; see paper for more information.
5. All assertions and clinical trial landscape data are curated from primary sources. You can read more about the curation process here.
