KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions
<i>RAS</i> mutations are among the most common oncogenic mutations in human cancers. Among <i>RAS</i> mutations, KRAS has the highest frequency and is present in almost 30% of non-small-cell lung cancer (NSCLC) patients. Lung cancer is the number one cause of mortality among...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/5/749 |
| _version_ | 1827752829962420224 |
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| author | Nastaran Karimi Seyed Javad Moghaddam |
| author_facet | Nastaran Karimi Seyed Javad Moghaddam |
| author_sort | Nastaran Karimi |
| collection | DOAJ |
| description | <i>RAS</i> mutations are among the most common oncogenic mutations in human cancers. Among <i>RAS</i> mutations, KRAS has the highest frequency and is present in almost 30% of non-small-cell lung cancer (NSCLC) patients. Lung cancer is the number one cause of mortality among cancers as a consequence of outrageous aggressiveness and late diagnosis. High mortality rates have been the reason behind numerous investigations and clinical trials to discover proper therapeutic agents targeting KRAS. These approaches include the following: direct KRAS targeting; synthetic lethality partner inhibitors; targeting of KRAS membrane association and associated metabolic rewiring; autophagy inhibitors; downstream inhibitors; and immunotherapies and other immune-modalities such as modulating inflammatory signaling transcription factors (e.g., STAT3). The majority of these have unfortunately encountered limited therapeutic outcomes due to multiple restrictive mechanisms including the presence of co-mutations. In this review we plan to summarize the past and most recent therapies under investigation, along with their therapeutic success rate and potential restrictions. This will provide useful information to improve the design of novel agents for treatment of this deadly disease. |
| first_indexed | 2024-03-11T07:28:37Z |
| format | Article |
| id | doaj.art-5cc01181700e422d858876b4396959be |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T07:28:37Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5cc01181700e422d858876b4396959be2023-11-17T07:27:38ZengMDPI AGCells2073-44092023-02-0112574910.3390/cells12050749KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and RestrictionsNastaran Karimi0Seyed Javad Moghaddam1Faculty of Medicine, Marmara University, Istanbul 34899, TurkeyDepartment of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA<i>RAS</i> mutations are among the most common oncogenic mutations in human cancers. Among <i>RAS</i> mutations, KRAS has the highest frequency and is present in almost 30% of non-small-cell lung cancer (NSCLC) patients. Lung cancer is the number one cause of mortality among cancers as a consequence of outrageous aggressiveness and late diagnosis. High mortality rates have been the reason behind numerous investigations and clinical trials to discover proper therapeutic agents targeting KRAS. These approaches include the following: direct KRAS targeting; synthetic lethality partner inhibitors; targeting of KRAS membrane association and associated metabolic rewiring; autophagy inhibitors; downstream inhibitors; and immunotherapies and other immune-modalities such as modulating inflammatory signaling transcription factors (e.g., STAT3). The majority of these have unfortunately encountered limited therapeutic outcomes due to multiple restrictive mechanisms including the presence of co-mutations. In this review we plan to summarize the past and most recent therapies under investigation, along with their therapeutic success rate and potential restrictions. This will provide useful information to improve the design of novel agents for treatment of this deadly disease.https://www.mdpi.com/2073-4409/12/5/749lung cancerKRASmolecular pathwaystherapy |
| spellingShingle | Nastaran Karimi Seyed Javad Moghaddam KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions Cells lung cancer KRAS molecular pathways therapy |
| title | KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions |
| title_full | KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions |
| title_fullStr | KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions |
| title_full_unstemmed | KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions |
| title_short | KRAS-Mutant Lung Cancer: Targeting Molecular and Immunologic Pathways, Therapeutic Advantages and Restrictions |
| title_sort | kras mutant lung cancer targeting molecular and immunologic pathways therapeutic advantages and restrictions |
| topic | lung cancer KRAS molecular pathways therapy |
| url | https://www.mdpi.com/2073-4409/12/5/749 |
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