The exploitation of the yeast Saccharomyces cerevisiae as a biological model for the investigation of complex molecular processes conserved in multicellular organisms, such as humans, has allowed fundamental biological discoveries. When comparing yeast and human proteins, it is clear that both amino acid sequences and protein functions are often very well conserved. One example of the high degree of conservation between human and yeast proteins is highlighted by the members of the RAS family. Indeed, the study of the signaling pathways regulated by RAS in yeast cells led to the discovery of properties that were often found interchangeable with RAS proto-oncogenes in human pathways, and vice versa. In this work, we performed an updated critical literature review on human and yeast RAS pathways, specifically highlighting the similarities and differences between them. Moreover, we emphasized the contribution of studying yeast RAS pathways for the understanding of human RAS and how this model organism can contribute to unveil the roles of RAS oncoproteins in the regulation of mechanisms important in the tumorigenic process, like autophagy.

This work highlights the potential synergistic effect of chitosan/γ-PGA nanoparticles with immunomodulatory cytokines, like IFN-γ, for anticancer therapy.

KRAS mutations are one of the most frequent oncogenic mutations of all human cancers, being more prevalent in pancreatic, colorectal, and lung cancers. Intensive efforts have been encouraged in order to understand the effect of KRAS mutations, not only on tumor cells but also on the dynamic network composed by the tumor microenvironment (TME). The relevance of the TME in cancer biology has been increasing due to its impact on the modulation of cancer cell activities, which can dictate the success of tumor progression. Here, we aimed to clarify the pro- and anti-inflammatory role of KRAS mutations over the TME, detailing the context and the signaling pathways involved. In this review, we expect to open new avenues for investigating the potential of KRAS mutations on inflammatory TME modulation, opening a different vision of therapeutic combined approaches to overcome KRAS-associated therapy inefficacy and resistance in cancer.

KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through the regulation of several downstream effectors. 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.

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