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In cancer cells, KRAS mutations confer the constitutive activation of this oncogene, stimulating cell proliferation, inducing autophagy, suppressing apoptosis, altering cell metabolism, changing cell motility and invasion and modulating the tumor microenvironment. In order to inhibit apoptosis, these oncogenic mutations were reported to upregulate anti-apoptotic proteins, including Bcl-xL and survivin, and to downregulate proteins related to apoptosis induction, including thymine-DNA glycosylase (TDG) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). In addition, KRAS mutations are known to induce autophagy in order to promote cell survival and tumor progression through MAPK and PI3K regulation. Thus, these mutations confer resistance to anti-cancer drug treatment and, consequently, result in poor prognosis. Several therapies have been developed in order to overcome KRAS-induced cell death resistance and the downstream signaling pathways blockade, especially by combining MAPK and PI3K inhibitors, which demonstrated promising results. Understanding the involvement of KRAS mutations in apoptosis and autophagy regulation, might bring new avenues to the discovery of therapeutic approaches for CRCs harboring KRAS mutations.<\/jats:p>","DOI":"10.3390\/cells11142183","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T22:06:00Z","timestamp":1657749960000},"page":"2183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1417-3418","authenticated-orcid":false,"given":"Anabela","family":"Ferreira","sequence":"first","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio-Sustainability (IB-S), Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2608-6511","authenticated-orcid":false,"given":"Fl\u00e1via","family":"Pereira","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio-Sustainability (IB-S), Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Engineering (INEB), University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0286-6639","authenticated-orcid":false,"given":"Celso","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-0272","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Engineering (INEB), University of Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9424-4150","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Sousa","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio-Sustainability (IB-S), Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-0630","authenticated-orcid":false,"given":"Ana","family":"Preto","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio-Sustainability (IB-S), Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30787","DOI":"10.18632\/oncotarget.5021","article-title":"Colorectal cancer-related mutant KRAS alleles function as positive regulators of autophagy","volume":"6","author":"Alves","year":"2015","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/sj.bjc.6605534","article-title":"Activating K-Ras mutations outwith \u2018hotspot\u2019 codons in sporadic colorectal tumours\u2014implications for personalised cancer medicine","volume":"102","author":"Smith","year":"2010","journal-title":"Br. 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