A Critical Review of the Prognostic and Predictive Implications of <i>KRAS</i> and <i>STK11</i> Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer
The Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) and serine/threonine kinase 11 (<i>STK11</i>) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, ther...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/6/1010 |
| _version_ | 1797593918114627584 |
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| author | Peter Manolakos Linda D. Ward |
| author_facet | Peter Manolakos Linda D. Ward |
| author_sort | Peter Manolakos |
| collection | DOAJ |
| description | The Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) and serine/threonine kinase 11 (<i>STK11</i>) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, there needs to be a review of the recent <i>KRAS</i> and <i>STK11</i> mutation literature to better understand the potential clinical applications of these genomic biomarkers in the current treatment landscape. This critical review highlights the clinical studies that have elucidated the potential prognostic and predictive implications of <i>KRAS</i> mutations, <i>STK11</i> mutations, or <i>KRAS/STK11</i> co-mutations when treating metastatic NSCLC across various types of treatments (e.g., immune checkpoint inhibitors [ICIs]). Overall, <i>KRAS</i> mutations are associated with poor prognoses and have been determined to be a valid but weak prognostic biomarker among patients diagnosed with NSCLC. <i>KRAS</i> mutations in NSCLC have shown mixed results as a predictive clinical biomarker for immune checkpoint inhibitor treatment. Overall, the studies in this review demonstrate that <i>STK11</i> mutations are prognostic and show mixed results as predictive biomarkers for ICI therapy. However, <i>KRAS/STK11</i> co-mutations may predict primary resistance to ICI. Prospective <i>KRAS/STK11</i>-biomarker-driven randomized trials are needed to assess the predictive effect of various treatments on the outcomes for patients with metastatic NSCLC, as the majority of the published <i>KRAS</i> analyses are retrospective and hypothesis-generating in nature. |
| first_indexed | 2024-03-11T02:15:20Z |
| format | Article |
| id | doaj.art-4be4f851b3d648238bc89aa2a57eff3d |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-11T02:15:20Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-4be4f851b3d648238bc89aa2a57eff3d2023-11-18T11:11:51ZengMDPI AGJournal of Personalized Medicine2075-44262023-06-01136101010.3390/jpm13061010A Critical Review of the Prognostic and Predictive Implications of <i>KRAS</i> and <i>STK11</i> Mutations and Co-Mutations in Metastatic Non-Small Lung CancerPeter Manolakos0Linda D. Ward1Healthcare Genetics and Genomics PhD Program, Clemson University, Clemson, SC 29634, USAHealthcare Genetics and Genomics PhD Program, Clemson University, Clemson, SC 29634, USAThe Kirsten rat sarcoma viral oncogene homolog (<i>KRAS</i>) and serine/threonine kinase 11 (<i>STK11</i>) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, there needs to be a review of the recent <i>KRAS</i> and <i>STK11</i> mutation literature to better understand the potential clinical applications of these genomic biomarkers in the current treatment landscape. This critical review highlights the clinical studies that have elucidated the potential prognostic and predictive implications of <i>KRAS</i> mutations, <i>STK11</i> mutations, or <i>KRAS/STK11</i> co-mutations when treating metastatic NSCLC across various types of treatments (e.g., immune checkpoint inhibitors [ICIs]). Overall, <i>KRAS</i> mutations are associated with poor prognoses and have been determined to be a valid but weak prognostic biomarker among patients diagnosed with NSCLC. <i>KRAS</i> mutations in NSCLC have shown mixed results as a predictive clinical biomarker for immune checkpoint inhibitor treatment. Overall, the studies in this review demonstrate that <i>STK11</i> mutations are prognostic and show mixed results as predictive biomarkers for ICI therapy. However, <i>KRAS/STK11</i> co-mutations may predict primary resistance to ICI. Prospective <i>KRAS/STK11</i>-biomarker-driven randomized trials are needed to assess the predictive effect of various treatments on the outcomes for patients with metastatic NSCLC, as the majority of the published <i>KRAS</i> analyses are retrospective and hypothesis-generating in nature.https://www.mdpi.com/2075-4426/13/6/1010<i>KRAS</i>mutations<i>STK11</i>co-mutation<i>KRAS/STK11</i><i>KL</i> |
| spellingShingle | Peter Manolakos Linda D. Ward A Critical Review of the Prognostic and Predictive Implications of <i>KRAS</i> and <i>STK11</i> Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer Journal of Personalized Medicine <i>KRAS</i> mutations <i>STK11</i> co-mutation <i>KRAS/STK11</i> <i>KL</i> |
| title | A Critical Review of the Prognostic and Predictive Implications of <i>KRAS</i> and <i>STK11</i> Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer |
| title_full | A Critical Review of the Prognostic and Predictive Implications of <i>KRAS</i> and <i>STK11</i> Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer |
| title_fullStr | A Critical Review of the Prognostic and Predictive Implications of <i>KRAS</i> and <i>STK11</i> Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer |
| title_full_unstemmed | A Critical Review of the Prognostic and Predictive Implications of <i>KRAS</i> and <i>STK11</i> Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer |
| title_short | A Critical Review of the Prognostic and Predictive Implications of <i>KRAS</i> and <i>STK11</i> Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer |
| title_sort | critical review of the prognostic and predictive implications of i kras i and i stk11 i mutations and co mutations in metastatic non small lung cancer |
| topic | <i>KRAS</i> mutations <i>STK11</i> co-mutation <i>KRAS/STK11</i> <i>KL</i> |
| url | https://www.mdpi.com/2075-4426/13/6/1010 |
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