Lecture notes
Cancer Oncogenes as Drug Targets
- Module
- Immunopharmacology
- Institution
- Nottingham Trent University (NTU)
Lecture notes based on cancer oncogenes used as drug targets for pharmaceutical drugs
[Show more]
Seller
Follow
Content preview
Week 26 – Cancer Oncogenes as Drug TargetsFinding Key Mutations: Diagnosis and Treatment:
Cancer cells have extensively rewired pathways for growth and survival that underlie the malignant
phenotype. Thus, a key to successful therapy is the identification of critical, functional nodes in the
oncogenic network whose inhibition will result in system failure, that is, the cessation of the
tumorigenic state by apoptosis, necrosis, senescence, or differentiation
Some mutated oncoproteins are frequently associated with specific cancers (Drivers):
Example Tumour Suppressors:
Many Benign Tumours can Become Malignant: Cancer is a Multistep Process:
Colon Cancer:
Normal colonic mucosa Loss of apc gene (chromosome 5) Promotes DNA replication Benign
(early) adenoma Oncogenic mutation of a ras gene, Growth factor independence Benign (late)
adenoma Loss of p53 gene (chromosome 17) Loss of a gene (possibly dcc) on chromosome 18,
Apoptosis not triggered Malignant invasive carcinoma
Promotes DNA replication, Growth factor independence, Apoptosis not triggered = Evading growth
suppressors, Sustaining proliferative signalling
Astrocytoma:
Normal tissue Loss of p53 gene Low grade tumour Loss of a cluster of genes on
chromosome 9 Higher grade tumour Multiplication of gene for epidermal growth factor
receptor (chromosome 7) Loss of one copy of chromosome 10 Most aggressive form of tumour
N.B. Most tumours are genetically unique – may assist personalised medicine
Some genes cause high frequency of altered protein products across tumour types
, Mutation (Genetic) Hotspots in Cancer Genes:
TP53 tumour suppressor protein is a cell cycle regulator
At codon 157 in TP53, G-T transversions are frequently seen in smokers’ lung cancers, but
not in never-smokers
Chromosomal (Genomic) Hotspot example:
The Philadelphia Chromosome and BCR-ABL fusion protein in CML
Oncogenes as Small Molecule Drug Targets:
Some mutations are more dominant/essential than others in inducing and progressing
cancers
These are attractive targets for drug design and are known as targeted therapies
Imatinib for chronic myelogenous Leukemia targets the tyrosine kinase signal transducer BCL-abl
Breast cancer therapy uses HER2 therapies targeting the Human epidermal growth factor 2
HER-2/neu oncogene
EGFR targeted therapies target Epidermal growth factor (EGFR) mutation in lung cancer and colon
cancer
BRAF inhibitors target BRAF mutations in melanomas
Vitrakvi (Larotrectinib) inhibits tropomyosin receptor kinase (TRK) inhibitor proteins produced by
NTRK fusion genes in multiple cancers
Oncogenes as Monoclonal Antibody (Biologic) Drug Targets:
Antibodies are glycoproteins that recognise specific antigens
Produced in vivo by plasma B cells of the adaptive immune system
A single B cell clone produces one specific antibody (monoclonal antibody/mAb)
Can be engineered in large quantities against tumour targets
Direct action by the antibodies can cause ligand blocking and receptor blocking of the
tumour
Antibody Drug Conjugates:
Combining mAb specificity for tumour antigen makes delivering cytotoxic compounds
directly to tumour cells less toxic
Antibody is internalised to deliver drugs, radionuclide agents
Cause DNA damage and tumour cell death
Precision (Personalised) Medicine Oncogene Case Studies:
Case Study 1 – Point Mutations/Deletions in the Epidermal Growth Factor Receptor Family of
Proteins
EGFR: A Growth Factor Tyrosine Kinase Receptor:
Acts via Epidermal growth factor ligand
EGFR is expressed by the proto-oncogene C-erbB-1 (also known as Her-1 or ErbB-1)
Family members are overexpressed in many tumour types (e.g., Her2-breast)
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller evanyoung. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for £2.99. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
57413 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy revision notes and other study material for 14 years now