Cancer Therapy Flashcards
What is basic vs applied research
Basic research tries to understand the natural world
Applied research tries to build upon an understanding to develop a useful end product e.g a new drug
What are the types of cancer therapy?
Surgery, Chemo/radiotherapy and targeted therapy
How successful is surgery in cancer patients?
physical removal of the tumour is the most successful treatment for many cancers but it cannot work for cancers that spread widely through the body
What is chemotherapy?
toxic chemicals which selectively kill dividing cells. These have some selectivity for cancer cells but have severe side effects
What are the different classes of chemotherapy?
Alkylating agents- alkylate molecules including DNA, blocking DNA replication and cell division
Anti metabolites- generally mimic nucleotides and are incorporated into RNA and DNA
Topoisomerase inhibitors and microtubule blockers
What is radiotherapy?
radiation kills DNA. Like chemotherapy this selectively kills dividing cells, but has major side effects
What is targeted therapy?
Drugs which selectively block the specific proteins which are known to be driving cancer
What are the few major successful targeted therapies?
- Tamoxifen for hormone dependent breast cancers (blocks the estrogen receptor)
- Vemurafenib for BRAF mutant melonoma (>50%) (inhibits the BRAF kinase)
- Trastuzumab (aka Herceptin) for HER2 positive breast cancers (blocks the HER2 receptor)
What are the successful immune therapy strategies?
- Removing cytotoxic T-lymphocytes from a cancer patient and engineering them to recognise cancer cells before putting them back in the patient
- Using drugs to block cell-cell interactions between cancer cells and immune cells which protect the cancer cells
How did Peter Nowell and David Hungerford show that genes cause cancer?
They made a DNA construct with the cancer associated bcr-abl fusion gene downstream of a promoter sequence to drive its expression
They injected this DNA into mouse cells and made transgenic mice expressing the bcr-abl gene
The mice got leukemia
What is a drug target?
To treat a disease it is normally by blocking the the function of a protein which is causing the disease
For example, if a mutated active oncogene is causing a cancer, then a drug which blocks the function of the protein encoded by that gene
The selected protein is called a DRUG TARGET
What is the principal of targeted therapy?
If CML cancer cells have a unique protein that makes them grow, a drug can be developed to kill only cells with that protein
How was Imatinib developed?
A screen was performed for inhibitors of the bcr-abl kinase
This drug targets the protein and blocks it
What is the second generation bcr-abl inhibitor?
Nilotinib
More potent
Often active against cancers that have a resistance against Imatinib
How can Imatinib be repurposed?
It also inhibits normal ABL and also the related kinase enzymes PDGF-R and KIT-R
Therefore it is a good drug to treat GIST which is driven in mutations of KIT-R
