Block 1 - Basic Cancer Science Flashcards
Explain why many common definitions of cancer are flawed, and highlight the main points of an improved definition
- NOT uncontrolled growth (that would be exponential, and would rapidly become trillions of cells)
- NOT ALL mutated cancer cells (only 35-65%, as the rest is stromal cells that have been coopted)
Cancer is complex, but in general:
1. Cancer cells have escaped normal limitations of external cue-driven cell division
2. They have modified their local environment to exceed natural defined tissue borders
3. Form a multicellular mass, driven by a transformed cancer cell
4. Have mechanisms to evade immune surveillance and cell death
What are the main external stimulants of cell growth?
- GFs (e.g., EGF, FGF) - molecules that bind to receptors, triggering an intracellular signal cascade that promotes cell growth and division
- ECM Components (e.g., collagen and laminin) - regulate cell growth and division by providing chemical and mechanical signals
- Hormones (e.g. estrogen and testosterone) - stimulate cell growth and division
What are the main limiters/regulators of cell growth?
Limiters: CHEMICAL MICROENVIRONMENT (oxygen level, pH, temperature, nutrient availability)
Regulators: CYTOKINES (small proteins released by immune cells - ILs and IFs can sometimes promote or suppress cell growth and division)
Note: IL1ß promotes angiogenesis, but reduces cancer cell proliferation
State the main processes by which cancer cells escape normal tissue boundaries
ECM Degradation - MMPs
ECM Remodelling - production and secretion of ECM proteins
ECM Crosslinking - makes ECM stronger and stiffer
ECM Receptors - cancer cells can express receptors, e.g., integrins, that bind to specific ECM
Angiogenesis - promote formation of new blood vessels
Describe what is meant by the three “E” words relating to immune surveillance
Elimination: When immune killer cells outnumber the damaged/infected/cancerous cells and eliminate them rapidly
Equilibrium: When cancer maintains its size or grows slowly
Escape: When cancer cells grow faster than they can be eliminated, so the cancer grows (sometimes after years of dormancy)
State the main types of cell death, and how this relates to cancer
APOPTOSIS, NECROSIS, AUTOPHAGY
Also Anoikis, Pyroptosis, Necroptosis, Parthonates, Ferroptosis
Cancer cells must develop mechanisms of resistance against ALL of these in order to grow and spread
E.g., mutations in genes that regulate apoptosis (e.g., p53), upregulation of anti-apoptotics (e.g., BCl2, MCl1), downregulation of proapoptotics (e.g., BAK, BAX), activation of survival signalling pathways (e.g., PI3K-Akt-mTOR, or RAS/RAF/MEK/ERK), altering balance between DRs and Ligands (e.g., FAS, TNFR1)
State the four (highlighted) types of cells that cancer can arise from, and the names of these types of cancer
Epithelial (line surfaces of internal organs and glands to form a barrier) -> CARCINOMAS, e.g., lung/colon/breast
Mesenchymal (some connective tissue) -> SARCOMAS, e.g., bone/leiomyo
Hematopoietic (cells that give rise to blood cells) -> LEUKEMIAS, e.g., CML
Lymphoid (type of WBC) -> LYMPHOMAS, e.g., Hodgkin/Non-Hodgkin
Name the 7 (mentioned) types of cancer models, and state what they are
- CELL LINES - cultured cancer cells taken from a patient
- ORGANOIDS - 3D cultures of cells derived from cell lines (slightly more heterogeneity)
- XENOGRAFTS - implant cells from cell lines into a mouse
- PATIENT-DERIVED XENOGRAFTS (PDXs) - xenografts of a patient’s tumour into a mouse
- TUMOUR-INDUCED MOUSE MODELS - genetically engineered mice to mimic human tumour
- ZEBRAFISH MODELS - genetically engineered fish to mimic human tumour
- OMICS-BASED MODELS - large-scale real world data sets
State some of the main pros and cons of Cell Lines as a Cancer Model
PROS:
- Cheap, ease of handling, supply
- Consistent characteristics, easily modified and scalable, easily modified
- Constant conditions
CONS:
- Genetic drift and mutation
- Artificial environment - not representative and may lose in vivo characteristics
- Homogeneous cultures; no gradients, 3D or TME
- Ethical concerns
State some of the main pros and cons of Organoids as a Cancer Model
PROS:
- Cheap, ease of handling, supply
- Consistent characteristics, easily modified and scalable, easily modified
- Constant conditions
- MORE HETEROGENEITY THAN CELL LINES + 3D
CONS:
- Genetic drift and mutation
- Artificial environment - not representative and may lose in vivo characteristics
- Homogeneous cultures
- Ethical concerns
- LESS REPRODUCIBLE, HARDER TO STUDY MECHANISMS
State some of the main pros and cons of Xenografts as a Cancer Model
PROS:
- Closer in vivo tumour biology (can study tumour host interactions)
- Better drug discovery and testing
- Lots of cell line variants
- Can study metastasis
CONS:
- Limited generalisability to humans
- No host immune system, TME differences
- More expensive
- Still relies on cell lines (ethics, homogeneous)
State some of the main pros and cons of PDXs as a Cancer Model
PROS:
- Closest representation of human tumour
- Patient-specific tumour-host interactions (personalised!)
- Can test multiple drugs and treatments + drug response is most predictive
CONS:
- Patient-specific, not broadly applicable
- No host immune system, TME differences, limited mechanistic insight
- Cost, technical expertise, slow
- Ethics
State some of the main pros and cons of Tumour-Induced Mice as a Cancer Model
PROS:
- Closer in vivo tumour biology (can study tumour host interactions)
- Better drug discovery and testing
- Can study metastasis
- Develops “naturally” in terms of time and TME
CONS:
- Not scalable, TME differences, limited reproducibility between animal models
- Takes months, high cost and expertise
- Ethics
State some of the main pros and cons of Zebrafish as a Cancer Model
PROS:
- Rapid, transparent development
- High-throughput + cheap
- Conservation of gene function across species
CONS:
- TME differences, limited reproducibility between animal models, limited understanding of fish tumours and immunity
- Technical expertise
- Few drugs discovered
- Ethics
State some of the main pros and cons of Omics as a Cancer Model
PROS:
- High-throughput + non-biased, ease of data generation, increased data accuracy
- Can study complex biological systems + integrate multiple layers of information
- Ethics!
CONS:
- Limited FUNCTIONAL analysis or mechanistic insight + cannot stand alone
- Needs large sample material
- Expensive
Summarise the trends in pros + cons across all the common cancer models
From cell lines -> Mouse models:
Increasing cost
Decreasing certainty of mechanism
Decreasing scalability + reproducibility
Increasing complexity + translatability + drug development
Since smaller masses are much harder to detect than large masses, how can they be detected in early stages?
We can’t simply screen for dense or oddly shaped ECM, so must use our understanding of cellular and molecular cancer biology, e.g.:
- The Warburg Effect (shunting of energy production to only glycolysis and increased uptake of glucose) -> can visualise tumours that have large amounts of glucose due to hyperactive GLUT1
(This is just one example)
State and briefly explain some of the factors that result in higher cancer incidence for males than females
- Riskier behaviours (smoking, drinking, less exercise)
- Biological/anatomical susceptibility (e.g., prostate, lung, colorectal)
- Delayed prognosis and treatment (less likely to seek medical attention)
- Occupational exposure (construction - asbestos; miners - coal dust; manufacturing - chemicals; agriculture - pesticides; firefighters - smoke; painters - solvents; drivers - diesel fumes)
- Genetic susceptibility due to X-linked genes (e.g., MAPK signalling pathway, necroptosis, metabolic pathways, carbon metabolism)
-> MULTIVARIANT CAUSES
-> EPIDEMIOLOGY studies distribution and determinants in cancer patients
What is the (mentioned) evidence that environment plays a more significant role than genetics in determining cancer prevalence?
Statistics regarding Japanese emigrants to Hawaii, and comparing them to Japanese people in Japan, and Hawaiians in Hawaii
(Incidence of most cancers is intermediate but closer to that of native Hawaiians than native Japanese)
-> Cancers are MOSTLY exposure driven
How many cancers are considered preventable, and what are the main causes associated with these?
Around 42%:
- Smoking (19%)
- Obesity (7.8%)
- Alcohol (5.6%)
- UV Radiation (4.7%)
- Physical inactivity (2.9%)
- Poor diet (1.9%)
How many people per 1000 are expected to get mouth cancer in their lifetime, and how does alcohol affect this?
No alcohol:
-> 5 per 1000
10.5 Units Per Week:
-> 6 per 1000 (extra 1)
22 Units Per Week:
-> 8 per 1000 (extra 3)
44 Units Per Week:
-> 16 per 1000 (extra 11)
Describe some of the ways in which alcohol can cause cancer:
- Breakdown of alcohol creates toxic by-products, e.g., acetaldehyde, which can damage DNA and proteins in cells, and increase risk of cancer
- Increases hormone levels, e.g., estrogen, which can stimulate breast cancer and others
- Inflammation, oxidative stress, and weakened immune system, can all promote tumours
Effects are REVERSIBLE, CONCENTRATION-DEPENDENT, and ACCUMULATED
Describe the current understanding of the correlation and causation between smoking and cancer
Clear correlation AND causation:
- Smoke contains over 5000 chemicals, many of which are harmful
- These enter lungs, and can affect entire body
- Some chemicals damage our DNA, while others impair DNA
repair
Being smoke-free can prevent 15 different types of cancer - most notably Lung cancer
This is REVERSIBLE and ACCUMULATED
Describe the current understanding of the correlation and causation between obesity and cancer
BMI is more complicated than smoking - it correlates with SOME cancers, but not all
It does not cause an increase in mutations, BUT:
- Fat cells increase INFLAMMATION and make extra HORMONES and GFs
- These cause cells in our body to DIVIDE more often
- This increases the chance of CANCER CELLS being made
- Which then continue to divide and cause a TUMOUR
Indirect causes:
- Chronic inflammation due to fat cell removal
- Insulin resistance -> More insulin and insulin-like GFs in blood
- Hormones, e.g., estrogen, testosterone, insulin
- Organ pressure -> structural changes, build-up of waste products
- Poor nutrition -> less antioxidants and more free-radicals
What is considered a DIRECT CAUSE of cancer?
Something that directly causes a MUTATION - either somatic or germline
What is named as the primary cause of treatment failure?
HETEROGENEITY:
- Different cell types with different mutations and genetic backgrounds give rise to a polyclonal tumour
- This can make treatment more difficult, as it is harder to target ALL of these cell types
- More exposure leads to more changes, and thus more variants
What are the 6 (mentioned) common things which contain carcinogens or mutagens - and what is the caveat?
Smoke, Grilled Meats, Candles, Tobacco, Paints, Dyes
All contain carbon-based carcinogenic agents, which can integrate into metabolic pathways and cause failures (e.g., DNA damage, mitochondrial dysfunction)
However, some are only active after processing in the liver
How do we test for mutagenesis?
THE AMES TEST
Quick, simple, inexpensive way to screen large number of chemicals for potential mutagenicity
- Mix test compound with homogenised rat liver (so enzymes can activate it)
- Add to Salmonella which are unable to grow without added Histidine in culture medium
- Count number of bacterial colonies which have undergone a mutation allowing them to grow without added Histidine
What are the positives and limitations of the Ames Test?
Positives:
- Quick, inexpensive, simple, and reliable
- High throughput
- Non-animal (instead uses a well-established model bacteria, Salmonella)
Limitations:
- Limited predictive power (cannot predict toxicity or specific human mutations)
- May not detect all mutagens (only frameshifts, only bacterial mutagens, not anything toxic)
- May give false positives (some things DO cause mutations in bacteria but NOT higher organisms)
Name some of the things found to contain Ames-Positive compounds
Chimney smoke
Benzene
Vinyl Chloride
Hardwood dust
Radium
Arsenic
Asbestos
Snuff
HRE
Second List:
Black pepper
Common mushroom
Celery
Rhubarb
Cocoa powder
Mustard + horseradish
Alfalfa sprouts
Burnt materials
Coffee
What links all the tumours with the highest mutational burdens?
- They all arise from tissues with high EXPOSURE (e.g., skin, lungs, etc.)
- Also often in tissues with high turnover (especially epithelia, e.g., oesophagus, stomach)
This trend supports the idea that environment is more important than genetics
How are mutational signatures obtained?
- Sequence entire cancer samples
- Note every possible base change (e.g., C>A, T>C, etc.)
- Also note triplicates around these base changes (e.g., ACA, ACC, CCA, etc.)
- Total of 96 triplicate + switch combinations
- Display on a bar graph total percentage of each specific change in the sample
Original study identified 21 tumour signatures - now 25
How can cancer signatures be used for omics?
- Identify which signatures are found in which types of cancer
- In some cases, can infer function (e.g., Signature 4 is the only one found in all Lung Cancers, therefore likely to be caused by smoking)
- However, there is no single clear cause of most signatures
This is non-biased omics, as categories are purely based on sequence changes
Can also map signatures back onto cancer types (i.e., which signatures are most common in a lung adenocarcinoma - 4/5/2/1B)
- Most signatures that have signature 7 ALSO have 1B
- DNA damage has a unique mutational signature that we can “follow up” - smoking has many different mutational pathways, due to the range of carcinogens in smoke, making it harder to identify causality
Describe how researchers broke down the signature data for lung adenocarcinomas to help resolve which specific signatures in the sample are linked to smoking
Broke down the data by smoking habits (i.e., non-smokers vs lifetime smokers vs reformed smokers)
-> Found that Sig4 is enriched among smokers compared to non-smokers, and is dose-dependent among reformed smokers
-> This is good evidence that Sig4 is a signature of smoking (though still not quite proof, as smokers may share OTHER behaviours that correlate)
-> To PROVE, would need a control experiment where epithelial cells are directly exposed to smoke, and the signature is searched for
Describe the experiment by which the gene Src was discovered (and what is significant about this gene?)
Chicken DNA and RSV DNA were heated together, then cooled - researchers then searched for duplexes formed by identical genes in the two genomes
Duplexes of c-Src with v-Src allowed Src gene to be discovered - first known PROTO-ONCOGENE
What are Oncogenes and Proto-Oncogenes?
A proto-oncogene is a normal cellular gene, which, when it undergoes a GoF mutation, becomes an ONCOGENE - i.e., a gene that drives cancer (for example, by stimulating proliferation or inhibiting apoptosis)
How do viral oncogenes (e.g., v-Src) arise?
Viral CAPTURE of proto-oncogenes:
When the viral DNA integrates into the host genome, it may insert next to a proto-oncogene
The viral gene and the proto-oncogene may then be co-translated (proto-oncogene is accidentally captured) to form a fused RNA transcript
The proto-oncogene is often damaged during this process, e.g., it may lose a regulatory domain (in the case of v-src, it has lost a 5’ regulatory component)
Now, if the viral oncogene is integrated into a host genome, it will drive cancer
Describe the Philadelphia Chromosome, and state why it is associated with CML
Following a translocation between chromosomes 9 and 22, there will be an abnormally long 9+ chromosome, and a very short 22- chromosome (Philadelphia chromosome)
On the Philadelphia Chromosome, there is a fusion gene which encodes the BCR-ABL fusion protein, leading to dysregulated Abl Kinase activity and therefore cancer (Chronic Myeloid Leukemia)
Explain why the BCR-ABL fusion protein leads to cancer
In the fusion protein, the N-terminal sequences of Abl are missing (as the chromosomal break occurs downstream of the 5’ coding region)
The fusion protein is a constitutively active tyrosine kinase, which activates the Ras pathway, stimulating proliferation and suppressing apoptosis
Describe another oncogenic form of Abl besides BCR-ABL, and explain how its activity differs from BCR-ABL
The v-Abl gene is missing the entire SH3 domain (whereas BCR-ABL is only missing part of the SH3 domain)
This means v-Abl is EXTREMELY oncogenic, and the protein it encodes has a higher kinase activity than BCR-ABL, therefore stimulating proliferation (and suppressing apoptosis) more strongly
v-Abl is also targeted to the membrane, due to myristoylation of GAG
Explain on a molecular level why the Bcr-Abl protein encodes a constitutively active protein
In the wild-type protein, a “latch” holds the protein in a clamped, inactive conformation, which requires phosphorylation of Y245 and Y412 to become active
However, in the fusion protein, the altered SH3 domain cannot hold/clamp the protein in the inactive conformation, therefore the active site is always exposed, and the protein is always active
Name the drug that is used to suppress constitutively active Abl kinase, and explain how it achieves this
GLEEVEC (AKA imatinib) - mimics ATP and binds in its binding site
This prevents ATP from binding in the same site, and inhibits the ability of Abl Kinase to phosphorylate its target protein
Explain simply how tumour suppressor genes were discovered
When normal cells were fused with cancer cells, the hybrid cell was Non-mutagenic
This showed that there was “something” (presumably a gene) in the normal cell which is capable of suppressing the cancer -> TSGs
Summarise what TSGs are and what they do
TSGs are genes which prevent cancer and tumour formation, and LoF mutations of which can lead to cancer
Some act as “brakes” on the cell cycle, while others act as guardians of the genome, stimulating repair of DNA mutations
Explain the importance of the Rb gene, and how it is related to familial cancer
Rb is a TSG which encodes pRb - an important transcriptional repressor which regulates the cell cycle up to the R point (in late G1)
Rb binds E2F (a TF) and prevents it from activating target genes, until Rb is phosphorylated and releases E2F
Null mutations are associated with Retinoblastoma (though additional mutations generally required - cooperativity)
If an individual is born with a germline mutation in one Rb allele on chromosome 13, they are predisposed to retinoblastoma, as only one somatic mutation is now required for complete loss of Rb (whereas sporadic retinoblastoma is far rarer)
Explain the importance of p53
It is a transcription factor which acts as a tumour suppressor by transducing many signals associated with damage and promoting many responses
It suppresses the G1 -> S phase transition, and results in G1 arrest upon DNA damage (also involved in 2 other checkpoints - replication and entrance into M)
It induces p21 (a cell cycle inhibitor), and can also induce apoptosis if repair is not successful
Explain the importance of HER2 and how it can be inhibited
Her2 is a proto-oncogene, and an RTK which is overexpressed in HER2-positive cancers (common in breast cancers)
HER2 activates the RAS pathway, therefore overexpression of HER2 leads to increased RAS activation
Two (mentioned) types of inhibition:
1. Inhibition of dimerization - Pertuzumab
2. Inhibition via direct antibody binding - Trastuzumab
Explain what is meant by co-operativity between oncogenes
One single oncogene is very unlikely to be able to drive cancer on its own, as cancer cells must undergo so many transformations to be able to form a tumour
Rather, it is the activation of MULTIPLE oncogenes that more commonly leads to cancer (“accumulation of genetic mutations”)
For example, mice with both oncogenic MYC and RAS were far more likely to develop a tumour than mice with either oncogene alone
How likely is a single oncogene to transform a cell into a cancer/tumour cell?
It is very difficult for any one oncogene to affect the wide range of processes necessary for cancer cell transformation (e.g., proliferation, evading cell death, evading growth suppressors, angiogenesis, immortality, invasion and metastasis, etc.)
However, due to the “hourglass signalling” of cells (i.e., many receptors and ligands feeding into a few key kinases and TFs, which then activate many gene and phosphorylation targets), a mutation in one of the major central signalling molecules can have significant effects, since they have so many downstream targets
Given the hourglass model of signalling described above, why do mutations in some RTKs have such major downstream effects?
Some receptors (e.g., EGFR and HER2) act as signalling hubs, activating a wide array of kinases and transcription factors -> LINK TO CELL SIGNALLING LECTURES IN BLOCK 2!
Summarise the structure and function of Myc in cells
Myc is a basic, ubiquitous helix-loop-helix transcription factor which functions in almost every cell
It is involved in a wide array of cellular functions, e.g., proliferation, apoptosis, differentiation and metabolism
It forms a heterodimer with a partner called Max -> the dimer complex then binds specific DNA sequences called E-boxes
Myc has a half-life of only around 20 minutes, and is usually rapidly degraded by the proteasome
Explain how and why Myc relates to cancer
Background: MYC is constitutively and aberrantly expressed in over 70% of human cancers (as shown by FISH staining with complementary DNA probe)
As well as being overexpressed, Myc is also stabilised and activated in many cancers (e.g., activated by ERK, also AKT1 inhibits GSK3ß which would normally inhibit MYC)
While in normal cells, Myc is involved in cell cycle control, when Myc becomes dysregulated it may bind aberrant non-target genes (e.g., due to their sequence resembling an E-box), and will show increased activation of low-affinity target genes.
Myc has “fingers in all the right pies,” meaning it plays a role in a wide-enough range of cellular functions that its dysregulation can significantly contribute to cancer development:
these functions include the cell cycle, signal transduction (via Wnt), transcription (via E2F), protein biosynthesis, microRNAs, DNA repair, cell adhesion + cytoskeleton (via a3ß1 integrins and cdc42), translation (via eIF2a), metabolism (via GLUT1) and more
How can Myc activity be targeted/decreased?
We can either target Myc directly (e.g., Omomyc displaces Myc from Max, preventing function of the heterodimer -> used in the clinic), or indirectly:
- Target stability of Myc protein
- Target translation (e.g., Rapamycin inhibits mTOR, other drugs target Akt or PI3K)
- Target transcription (by inhibiting BRD4, CDK7 or CDK9)
None of these indirect methods are really used in the clinic, although there are trials for PI3K inhibitors as part of combination therapy)
Do Myc and RAS show synergetic co-operation in cancer cells?
This depends on the type of cancer model:
- In a lung cancer mouse model, they do not synergise, and the tumour free survival with both mutant KRAS and MYC is between that of mutant KRAS alone and MYC alone (moderate incidence)
- However, in a lymphoma mouse model, the two mutations show significant synergy, as the tumour free survival when both MYC and KRAS are mutated is significantly lower than for either KRAS or MYC alone)
This shows that, although many pathways LOOK like they should combine, this doesn’t mean they always do - it depends on the cancer and tissue background
What is meant by “Autocrine-driven co-operation and signal diversification”
For some mutant signal proteins/nodes, they don’t just activate downstream pathways, but also induce production of ligands, which can activate RTKs in the same cell with diverse intracellular docking sites, thereby activating a wider range of pathways
(e.g., mutant RAS -> MAPK pathway -> TGFa ligand production -> activates EGFR -> Grb2/Shc/Cbl/STAT3/PLC-y/JAK2/SHP1 etc)
Besides MYC and RAS, what other common example of oncogene co-operation was highlighted in the lecture, and what point was it meant to demonstrate?
BRAF and PI3K (or PTEN) mutations:
There are two canonical branches of growth and survival pathways (MAPK and PI3K, both activated by RAS)
It is common to find mutations in both of these pathways -> ESPECIALLY frequent when targeted inhibitors have been used to block one branch, there are often mutations in the other branch to “offset” this
A common related phenomenon is RTK swapping or doubling down:
-> Mutant EGFR and other RTKs synergise to activate similar pathways, and this often occurs in response to inhibition of one RTK, with another mutation “offsetting” this
In what way do RAS and MYC co-operate as oncogenes, BESIDES through signal transduction
When both RAS and MYC are mutated, they co-operate to suppress immune surveillance, thus altering the TME and promoting tumour growth
Why does the issue of polyclonal tumours relate to the topic of Lecture 8?
In a polyclonal tumour, the different oncogenic drivers in the different clonal cells comprising the tumour may show co-operation with each other (e.g., via autocrine and paracrine signalling of different ligands and GFs)
This further increases the heterogeneity of these tumours and makes them harder to treat, as a wider array of pathways are continuously activated in all the tumour cells
What is gene expression profiling and how is it useful in the context of cancer?
Gene expression profiling is a technique by which the expression of thousands of genes can be simultaneously investigated and displayed
This allows far more accurate classification of tumours, and can be used to predict a patient’s clinical outcome and treatment pathway
Tagline: “Classify tumours by gene expression, not just which mutations they have”
HOWEVER, the sheer amount of data in a full gene expression profile is too complicated to take account of all at once, so smaller-scale molecular profiling can be used to investigate the expression of a couple of genes (e.g., HR and HER2)
What is the key example of molecular profiling discussed in the lecture, and how can it be used to predict patient outcomes?
HR/HER2 in breast cancer
There are four main subtypes of breast cancer:
- HR+/- classifies whether the tumour cells express receptors for the hormones oestrogen and progesterone, which promote growth of HR+ tumours
- HER2+/- indicates expression of human epidermal growth factor receptor 2, an RTK which plays a role in growth, differentiation and survival
HER2 overexpression/amplification can lead to increased growth and division, and HER2+ cancers are typically treated with targeted therapy (e.g., trastuzumab/Herceptin and pertuzumab/Perjeta)
HR-/HER2- tumours have the lowest survival rate, followed by HR-/HER2+
Immunohistochemistry for ER, HER2 and Ki67 can provide subjective profiling of breast cancer cells into several classes
Molecular profiling (e.g., ER+ LuminalA, ER+LuminalB, ER-/HER2+ and Basal-Like) can determine the most beneficial path of treatment [note: if a patient is ER- AND HER2-, i.e., basal-like, then their treatment options are a lot broader, and more tests will be needed to find out the specific gene expression of the tumour and how best to treat it, whereas other groups can be specifically targeted with Herceptin or Tamoxifen or Imatinib, etc.]
