Targetted Cancer Therapies Flashcards
1
Q
Cancer arises from…
A
-Imbalance of genetic events
-Tumor suppressor gene pathways
VS
-Oncogene pathways
2
Q
Oncogenes
A
- Become activated - gain of function mutations
- Involved in cell signal transduction and cell death signaling (inhibition of apoptosis)
- Originally found in viruses, picked up protooncogene from host cell
- Provide druggable targets
3
Q
Tumor Suppressor Genes
A
- Become inactivated - loss of function mutations
- Often involved in stabilizing genome, cell cycle regulation, and cell environment regulation
- Categorized as caretakers/gatekeepers/landscapers
- Difficult to target for pharmacotherapy
4
Q
Kinases
A
- Enzyme that catalyzes phosphate transfers on amino acids
- Altered activity often seen resulting in increased cellular proliferation/survival
5
Q
Oncogene Activation Methods
A
- Chromosomal translocations: abnormal expression or creates chimeric protein with unique activity
- Mutations: point mutation that changes the amino acid sequence of the coded protein
- Amplification: multiple copies of a gene leading to overexpression
- Dysregulation: overexpression due to mutations in the promoter region
- Proviral insertion: viral insertion alters gene expression
- Others: alterations in phosphorylation
6
Q
Chromosomal Translocation Examples
A
- Associated with Burkitt’s Lymphoma
- Most common variant: t(8;14)(q24;q32)
- Involves Ig genes (chr. 14) and c-myc (chr. 8)
- Many other examples involving many different chromosomes
7
Q
BCR-ABL Kinase Inhibitiors
A
- Activation of ABL oncogene occurs from translocation between chromosomes 9 and 22
- Associated with chronic myeloid leukemia
- Use Imatinib, dasatinib, nilotinib, bosutinib, or ponatinib
8
Q
Mutation Examples - KIT
A
Could result in…
- Mutation of an oncogene, occurs as an early cancer development event and is important for maintaining cancer phenotype (oncogene addiction)
- Drug resistance: occur after drug therapy is initiated, may takes months to years to develop, require changing drug used to inhibit activity
9
Q
EGFR
A
- Epidermal Growth Factor Receptor
- Several drugs developed to inhibit these receptors
- Used in a variety of cancers (non-small cell lung cancer, breast, pancreatic)
10
Q
BRAF and MEK Inhibitors
A
- BRAF-I used to treat melanoma
- EX: Vemurafenib, Dabrafenib (first’s name comes from V600E mutated BRAF inhibition)
- MEK-I: Used to treat melanoma
- EX: Cobimetinib and Trametinib
11
Q
P13K Inhibitors
A
- Blocks the phosphorylation of 3’ hydroxyl group of inositol ring used to cell signal transduction
- Used to treat certain blood cancers
- EX: Copanlisib, Idelalisib
12
Q
mTOR Inhibitors
A
- Mammalian target, sensor for cellular nutrient, oxygen, redox, and energy levels
- mTORC2 phosphorylates Akt
- Used to treat breast cancer
- EX: Everolimus
13
Q
ALK Inhibitors
A
- ALK inhibitors or mutant ALK inhibitors
- Used to treat non-small cell lung cancer
- ALK Inhibitors: Alectinib, Brigatinib
- Mutant ALK Inhibitor: Crizotinib
14
Q
BTK Inhibitors
A
- Bruton’s tyrosine kinase plays key role in B-cell development
- BTK Inhibitor: Acalabrutinib
- Mutant BTK Inhibitor: Ibrutinib
15
Q
CDK Inhibitor
A
- Cyclin-dependent kinases function in phosphorylating proteins involved in cell cycle progression
- Palbociclib in a CDK-4 & 6 inhibitor
- Used to treat ER+, HER2 negative breast cancer
