Question

In: Biology

Mutation of EGFR or Ras protein often leads to cancer. For EGFR mutated cancer, antibodies have...

Mutation of EGFR or Ras protein often leads to cancer. For EGFR mutated cancer, antibodies have been developed to inhibit EGFR signaling. However, no effective treatment has been developed yet. Why it might be difficult to develop specific antibodies against Ras?

Solutions

Expert Solution

ANSWER :- About a third of all human Cancers harbour mutations in one of the K-, N- , or HRAS genes that encode an abnormal RAS protein locked in constitutively activated state that to drive malignant transformation and tumor growth. Despite more than three decades of intensive research aimed at the discovery of RAS- directed therapeutics, there are no FDA approved drugs that are broadly effective against RAS-driven cancers. Although RAS protein are often said to be "undruggable" there is mounting evidence suggesting that it may be feasible to develop direct inhibitors of RAS protein. The reason behind that is :-

  • RAS will be used when two or more isoforms may be involved. RAS protein are monomeric enzymes with modest GTPase activity, but which bind GTP and GDP with high affinity.
  • The active, GTP-bound form of RAS has been described as a "coiled spring", which in turn activates effector proteins. Thus, RAS protein are important regulators of multiple aspects of normal cell growth and physiology, as well as malignant transformation.
  • Most importantly that the RAS mutations develop spontaneously in tumors that become resistant to radiation and/or chemotherapy, or targetted therapies, including receptor tyrosine kinase inhibitors that activates the RAS pathway.

That is why it is difficult to develop specific antibodies against RAS.


Related Solutions

Ras is a GTP-binding protein that is often mutated in cancer cells. Normal cells are stimulated...
Ras is a GTP-binding protein that is often mutated in cancer cells. Normal cells are stimulated to divide by receiving a signal from a growth factor through a receptor tyrosine kinase. When the receptor tyrosine kinase binds the growth factor, Ras is stimulated to bind GTP. Ras in turn activates proteins that promote cell proliferation. A common mutation in cancerous cells causes Ras to behave as though it were bound to GTP all the time. Suppose that there is a...
A mutation in the ras cellular oncogene can cause cancer when it is in the heterozygous...
A mutation in the ras cellular oncogene can cause cancer when it is in the heterozygous condition, but a mutation in the RB tumor suppressor gene can cause cancer only when it is in the homozygous condition. What does this difference between dominant and recessive mutations imply about the roles that the ras and RB gene products play in normal cellular activities?
28) Ras is a ________, which can ______ cancer development when activated constitutively. A) Adapter protein...
28) Ras is a ________, which can ______ cancer development when activated constitutively. A) Adapter protein of the insulin signaling pathway, promote B) Monomeric G-protein, suppress C) Heterotrimeric G-protein, promote D) Monomeric G-protein, promote 29) Which of the following is not an event happened during prophase? A) The nuclear lamina is disassembled by depolymerization of the lamin filaments. B) Fragmentation of Golgi complex and ER. C) Chromosomal material condenses to form compact mitotic chromosomes D) Chromosomal microtubules attach to kinetochores....
1. Ras is a ________, which can ______ cancer development when activated constitutively. a. adaptor protein...
1. Ras is a ________, which can ______ cancer development when activated constitutively. a. adaptor protein of the insulin signaling pathway, promote b. monomeric G protein, suppress c. heterotrimeric G protein, promote d. monomeric G protein, promote 2. The _____ kinase is essential in yeast for adding an inhibitory phosphate group to ____ when it is bound to a cyclin, which prevents the cell from entering mitosis until all conditions of the checkpoint are cleared and the phosphate group is...
A functional mutation of the Apoc-2 protein leads to Hyperlipoproteinemia. This disorder is characterized by increased...
A functional mutation of the Apoc-2 protein leads to Hyperlipoproteinemia. This disorder is characterized by increased lipoproteins(eg. chylomicrons) in the blood. Explain as to how a functional mutation of Apoc 2 leads to this disorder.
what are the major groups of genes that when mutated can cause cancer, and include the types of mutations that can change their protein structure.
  what are the major groups of genes that when mutated can cause cancer, and include the types of mutations that can change their protein structure. your assigned gene (C-KIT). Focus on the group of cancer-causing genes that this gene belongs to, its normal function, and why the mutation can lead to the cell cycle becoming out of control. Is your mutated gene inherited, or does it become mutated throughout a person’s lifetime? If you could develop a drug that...
what are the major groups of genes that when mutated can cause cancer, and include the types of mutations that can change their protein structure.
  what are the major groups of genes that when mutated can cause cancer, and include the types of mutations that can change their protein structure. your assigned gene (P53). Focus on the group of cancer-causing genes that this gene belongs to, its normal function, and why the mutation can lead to the cell cycle becoming out of control. Is your mutated gene inherited, or does it become mutated throughout a person’s lifetime? If you could develop a drug that...
Ras nucleotide exchange is stimulated by ___. A mutation in RTK receptor that allows the receptor...
Ras nucleotide exchange is stimulated by ___. A mutation in RTK receptor that allows the receptor to bind the ligand and pair with a wild-type receptor but blocks signal transduction is classified as a ________ ________ mutation, whereas a mutation that activates RTK pairing signal transduction even in the absence of ligand is classified as a ______________ _______ mutation. PTEN is a phosphatase that removes a phosphate group from ____, thereby preventing its activation of Akt kinase.
Explain the mechanism by which a missense mutation in the RAS gene that impairs the GTPase...
Explain the mechanism by which a missense mutation in the RAS gene that impairs the GTPase activity of the RAS protein promotes cancer cell division.
How does Aspartic acid mutated to glycine? What are the effects of the mutation to a...
How does Aspartic acid mutated to glycine? What are the effects of the mutation to a protein? What would is change
ADVERTISEMENT
ADVERTISEMENT
ADVERTISEMENT