Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer
Abstract
:1. Introduction
2. Allosteric RAS Inhibitors
3. Inhibition of Post Translational Modification of RAS
4. RAF Inhibitors
5. MEK Inhibitors
6. ERK Inhibitors
7. Resistance to MEK Inhibitors in RAS Mutant Cancers
8. Autophagy as a Resistance Mechanism to MAPK Inhibition
9. Combined MAPK and Autophagy Inhibition Is Synergistic in RAS Mutant Cancer
10. Clinical Trials with Autophagy and MAPK Inhibitors in RAS Mutant Cancers:
11. Open Questions
12. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Treatment | Condition | Phase | ClinicalTrials.gov Registration |
---|---|---|---|
Sotorasib + Trametinib + Others | Advanced KRAS G12C Solid Tumors | I/II | NCT04185883 |
Sotorasib + Docetaxel | Advanced KRAS G12C NSCLC | III | NCT04303780 |
JAB-21822 + Cetuximab | Advanced KRAS G12C NSCLC + CRC | I/II | NCT05002270 |
JAB-21822 | Advanced KRAS G12C NSCLC + CRC | I/II | NCT05009329 |
Treatment | Condition | Phase | ClinicalTrials.gov Registration |
---|---|---|---|
Binimetinib and HCQ | Stage IV KRAS mutant NSCLC | II | NCT04735068 |
Binimetinib and HCQ | Stage IV Pancreatic adenocarcinoma | I | NCT04132505 |
Trametinib and HCQ | Stage IV Pancreatic adenocarcinoma | I | NCT03825289 |
Trametinib and HCQ | Stage IV KRAS mutant biliary tract carcinoma | II | NCT04566133 |
Cobimetinib + Atezolizumab + HCQ | Stage IV KRAS mutant gastrointestinal cancers | I/II | NCT04214418 |
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Lee, J.J.; Jain, V.; Amaravadi, R.K. Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer. Int. J. Mol. Sci. 2021, 22, 12402. https://doi.org/10.3390/ijms222212402
Lee JJ, Jain V, Amaravadi RK. Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer. International Journal of Molecular Sciences. 2021; 22(22):12402. https://doi.org/10.3390/ijms222212402
Chicago/Turabian StyleLee, Jennifer J., Vaibhav Jain, and Ravi K. Amaravadi. 2021. "Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer" International Journal of Molecular Sciences 22, no. 22: 12402. https://doi.org/10.3390/ijms222212402