L7 - Aberrant cell signalling in cancer provides targets for therapeutic intervention Flashcards
What does aberrant mean?
Diverging from the normal type
How do we identify appropriate therapy for an individual cancer patient?
There are common mutations in lots of cancer types
There are also subtle gene differences that can give 1 patient a lot more aggressive tumour than another
We need to be able to identify these differences to give the optimum treatment
Tumour heterogeneity in diagnostics & metastatic spread
The main problem we have is the fact that tumours can be very heterogenous
There are differences between individuals, and areas of a single tumours are also different – can create problems in trying to identify which is the most important clone to treat
Do we want to target one or all of them? Which one is the driver of the cancer?
Does the primary cancer usually kill the patient?
NO
Its more likely to be due to the cancer metastasising
Step wise progression of cancers
tumours will grow and can be released into the blood stream
Alternative hypothesis for the progression of cancers
Tumour starts releasing cells at an early stage and disseminated into the blood stream, as they are released they are evolving all the time
The tumour cells will lie dormant in the body for long periods of time – this is true for lots of breast cancer patients
Issues with cancer drugs
Lots of drugs will kill the primary tumour, but in later years they will come back as they’ve been dormant – acquire mutations to form the secondary tumours & metastasize
Genomic alterations that cause cancer
- Point mutations
- Gene amplification
- Deletions
- Altered gene expression
- Translocations
- Epigenetic modifications
- Aberrant RNA splicing
- microRNAs
Genomic perturbations promote cancer cell survival affecting the hallmarks of cancer by altering:
- Cell cycle control
- Differentiation
- Tumour vascularisation
- DNA repair
- Apoptosis
- Metabolism
Breast cancer classification
Breasts are made of many ducts & lobes
Different types of cancer can occur in breasts
Can define breast cancer into carcinomas or sarcomas
Carcinoma types
Epithelial
Ductal carcinomas in situ
– Cancers that will grow to a certain size & then no further (CIS)
– Don’t tend to be metastatic
– Don’t form their own blood supply so cant become that aggressive
Lobular carcinomas in situ
– More aggressive
– Develops into the lobes of the breasts
Invasive ductal carcinomas
– Rare invasive ductal subtypes
Sarcoma
Stromal (connective tissue)
• Develop into the stromal compartment
Examples:
• Phyllodes tumour
• Angiosarcoma
Breast cancer subgroups
Based the subgroups on the expression of certain genes
The breast is an oestrogen-dependent organ
Removal of ovaries to block oestrogen production was previously used as an effective therapy
Subgroups: • Estrogen Receptor positive (70%) • ERBB2 (HER2) positive (10%) • Triple negative (lack ER, PR + ERBB2) (15%) • Normal-like (5%)
Estrogen Receptor positive (70%)
Many woman with breast cancer express the oestrogen receptor
Within this group of ER breast cancer they can be divided into luminal A & B tumours which have slight differences between them:
– Luminal A – more favourable prognosis for a woman
– Luminal B
Tamoxifen treatment (anti-oestrogen)
ERBB2 (HER2) positive (10%)
Woman who express the ERBB2 transmembrane receptor
Treatment for this would be the antibody trastuzumab which binds to the HERB2 receptor & blocks its action