Question

What other effects can ras activation have on the cell, apart from Raf activation? Be specific about mechanisms and outcomes. (80-200 words)

Outline the mechanistic pathway from a new mutation happening at Ras position 12 in a human cell, to the promotion of cancer. (150-300 words)

Answer 1

answers:

1st part :effects can ras activation have on the cell, apart from Raf activation? Be specific about mechanisms and outcomes.ffects can ras activation have on the cell, apart from Raf activation? Be specific about mechanisms and outcomes.

answer:

RAF inhibitors have made a significant impact on the lives of melanoma patients whose tumours express the BRAFV600E oncogene. As with most other cancer therapeutics, efficacy is associated with side effects and in the case of RAF inhibitors, induction of secondary malignancies is a significant concern. However, it appears that the vast majority of cases with the risk to the patient is relatively low, although the clinical experience with these agents is still very early. The pharmacological behaviour of these inhibitors may not have been anticipated but the observations and follow-up mechanistic studies have led to a deeper understanding of RAF–MEK–ERK signalling. These insights will guide future drug development efforts to create better inhibitors that may be optimised towards a tailored pharmacological profile.

2nd part: Outline the mechanistic pathway from a new mutation happening at Ras position 12 in a human cell, to the promotion of cancer

We have identified differences in mutational spectra between the three Ras isoforms that are likely to be a consequence of multiple interacting intrinsic and extrinsic factors. Tissue-specific comparison between isoforms indicates that these are not simply due to differences in mutagen exposure that could create the heterogeneity observed across a single isoform. We have identified genetic, epigenetic and protein based mechanisms that may contribute to generating these mutational spectra. The expression of three almost identical Ras isoforms from separate gene loci presents a unique opportunity to deconvolve the effects. Consequently, they represent the ideal model system for probing generic questions about mutagenesis, carcinogenesis, signalling network integration and how contextual influences such as relative abundance, tissue expression and subcellular localization modulate these complex phenomena. We anticipate important advances in our understanding of these areas in the near future with the development of large scale screening platforms, isogenic model systems and a more systematic approach to analysing the isoforms in parallel.