RTK's and Cancer Lecture 2 Flashcards
Why should veterinarians be interested in receptor tyrosine kinases?
RTKs interact with growth factors and initiate events that lead to normal cell proliferation. RTKs can be mutated to be over-activated and result in uncontrolled cell growth, which is a primary underlying cause of cancer. RTK’s are attractive targets for drugs used to treat hyper proliferative conditions and anti-cancer drugs.
What is Palladia? How does it work? What does it do?
Palladia was the first anti-cancer therapy drug FDA approved for dogs. It inhibits receptor tyrosine kinases, specifically KIT, by being a competitive inhibitor of ATP. Without ATP binding to the kinase domain of the KIT RTK, the kinase cannot be activated.
_____ _____ in anti-cancer treatment are designed to interfere with specific molecules necessary for cancer cell proliferation and cancer progression. What is the difference between this and chemo?
- Targeted Therapy
- Chemotherapy indiscriminately kills any rapidly dividing cell
What can mutations in genes encoding receptor tyrosine kinases result in?
changes in the amino acid composition which can alter the RTK protein conformation and result in ligand independent activation
A _____ is a change or alteration in normal DNA nucleotide sequences and is often a single nucleotide change
Mutation
What is the result of ligand independent activation of RTK?
No ligand is needed for the RTK to be activated, which results in continuous signaling causing persistent growth stimulation
What kind of mutation causes an RTK to be ligand independent?
A point mutation, which is a change in a single nucleotide
What are the two scenarios that can result from a mutation in the genes of an RTK
- the Point mutation alters the 3 codon reading frame and results in the incorporation of a new amino acid, causing the RTK to spontaneously form dimers that continuously activate the RTK without a ligand
- The mutation can cause synthesis of an RTK protein without an extracellular domain, and the RTK is always on
_____ is the #1 natural cause of death in dogs and cats in the U.S. and is a disease of genetic alterations
Cancer
What has been identified as a key early event in cancer development and progression?
Uncontrolled cell growth or increased proliferation
Cancer is a disease of _____ _____ that can enhance ____ or prolong cell ______.
- Genetic Alterations
- Proliferation
- Survival
Which two broad classes of genes are linked to cancer?
Oncogenes and tumor suppressor genes
A _____-_____ encodes a protein that promotes normal or regulated cell proliferation, while an _____ is a mutated or genetically altered version that exhibit enhanced functional capacity, or a ____ ____ ____ mutation.
- Proto-Onocogene
- oncogene
- Gain of Function
A _____ _____ _____ encodes a protein that inhibits or blocks cell proliferation.
Tumor Suppressor Gene
Genetic alterations that reduce the function of tumor suppressor genes included _____ and _____ and are called ____ ____ ____ alterations.
- Mutations
- Deletions
- Loss of Function
