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A single amino acid change in RAS eliminates its ability to hydrolyze GTP, even in the presence of a GTPase-activating protein (GAP). Roughly 30% of human cancers have this change in RAS. You have identified a small molecule that prevents the dimerization of a receptor tyrosine kinase that signals via RAS. Would you expect this molecule to be effective in the treatment of cancers that express this common, mutant form of RAS? Why or why not?

User TJA
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2 Answers

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Final answer:

Mutant RAS protein with inhibited GTPase activity leads to continuous activation of cell proliferation pathways, contributing to cancer. A small molecule that prevents RTK dimerization is unlikely to be effective in treating cancers with this mutant RAS, as RAS mutation causes constitutive downstream signaling independent of RTK activity.

Step-by-step explanation:

The question revolves around the functionality of RAS, a G-protein that plays a crucial role in cell signaling, particularly in the context of cancers where its GTPase activity is inhibited. As a result, the RAS protein can no longer hydrolyze GTP into GDP, leading to a continuously active state. The consequence of this mutated RAS is the persistent activation of downstream signaling pathways, such as the MAPK kinase cascade, which in normal circumstances would promote cell proliferation and differentiation only when required. However, in the case of the RAS mutation, the signaling leads to uncontrollable cell division, contributing to the development and progression of cancer.

The small molecule in question, which prevents the dimerization of receptor tyrosine kinase (RTK), might not be effective in the treatment of cancers with the mutant form of RAS for a couple of reasons. First, the mutation in RAS renders it active regardless of RTK signaling since it cannot switch off due to its inability to hydrolyze GTP. Second, the cancer cells expressing the common RAS mutation would continue to proliferate uncontrollably despite the inhibition of RTK dimerization because the cascades downstream of RAS are already constitutively active.

User Manushi
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Answer:

1. According to the question, when a change in an oncogenic gene is induced by a molecule, many types of cancer are expected to improve by inducing these new processes, so the answer is yes.

2. the process can be explained by the reaction binding to RTK that leads to the generation of RTK dimers, later it undergoes autophosphorylation and activation which triggers an activating response on RAS that is involved in the generation of cancer cells, when all these events occur, if the molecule interferes, it is expected that the response will not be triggered until the final result that would be the prevention of cancer

User Tom McQuarrie
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