Systemic Clinical Cancer Treatment (1) Flashcards
Give examples of loco-regional therapies
Surgery
Radiotherapy
What are systemic medicines?
Cancer medicines
Why is systemic cancer therapy important?
Most patients have metastasis already at the time of diagnosis
Loco-regional therapies cannot target these
How big does a tumour have to be to be detected clinically?
~2cm
How big does a tumour have to be to be treated with radiotherapy?
~1cm
What is it called if the tumour is below the clinical detection size?
Micrometastatic disease
How many cells are in a 1cm tumour mass?
~1 million
How many cells are in a 2cm tumour mass?
~1 billion
Name the types of systemic therapies
Cytotoxic chemotherapy
Targeted agents
Endocrine therapy
Immunotherapy
What is endocrine therapy?
Anti-oestrogen and anti-androgen therapy for hormone driven cancers - breast and prostate
Why is combination therapy advantageous?
Decrease the chance of resistance or delays its emergence
What is the issue with combination therapy?
Toxicities can be severe
Need to lower dosages
What are the two types of endocrine therapies?
Receptor antagonists
Reduce the production of oestrogen and androgen
Name examples of endocrine therapy, receptor antagonists
Oestrogen - Tamoxifen
Androgen - Cyproterone
Name examples of endocrine therapy, reducing the production of oestrogen and androgen
Gonadotrophin Releasing hormone analogues (oestrogen and androgen) Aromatase inhibitors (oestrogen only)
Advantages of endocrine therapies
Relatively few side effects
Well tolerated
Disadvantages of endocrine therapies
Can take up to 3 months to have a clinically beneficial effect
Long term side effects:
- osteoporosis
- cardiovascular disease
Why is osteoporosis a side effect?
Bone mass is dependent on oestrogen and androgens
Who may not benefit from endocrine therapies?
People will advanced stage disease who need a fast response
What do small molecule drugs end in?
‘-nibs’
What do monoclonal antibody drugs end in?
‘-mabs’
Name a targeted drug for renal cell carcinoma and hepatocellular carcinoma and how it works
Sunitinib
Anti-angiogenic drugs which target VEGF and VEGFR
What are the advantages of targeted drugs?
More effective than chemotherapy
Less side effects
Can be used in combination with chemotherapy without increasing toxicity
Can be used in patients who are resistant to chemotherapy
Name a targeted drug which can be used in NSCLC patients who are unfit for chemotherapy
Erlotinib - targets EGFR
Name a targeted drug which is used in combination with chemotherapy
Trastuzumab (Herceptin) for HER2+ breast cancer
Name a targeted drug which can be used in CRC patients who are resistant to chemotherapy
Cetuximab - targets EGFR
What is the new molecular classification of cancer?
Where cancer can be broken up into molecular subgroups, based on biomarkers, and these molecular subgroups tell you what to target
What do tumour cells express on their surface?
Neoantigens
What are neoantigens important for?
Allowing the immune system to prevent early tumours (immune surveillance)
What are clinical immunotherapies?
Immune checkpoint inhibitors
- CTLA-4 inhibitors
- PD-1/ PD-L1 inhibitors
Name a CTLA-4 inhibitor and describe it
Ipilimumab
Monoclonal antibody
Inhibits CTLA-4 so B7 binds to CD28 (co-stimulatory molecule)
Why do tumour cells express Pd-L1 on its surface?
To inhibit T cell activation
What increases the effectiveness of immune checkpoint therapies?
High mutational burden
Name a PD-1 inhibitor
Pembrolizumab
What is the main benefit of immune checkpoint therapy?
The response appears to be long term
How long to immune therapies take to be effective?
~6 months
after see tumour growth in this time
What auto-immune toxicities are associated with immune checkpoint therapies?
Colitis
Pneumonitis
Endocrinopathies
What is the next steps for immune checkpoint therapies?
Combination therapies
Biomarkers
New immune checkpoint therapies
Why may combining chemotherapies with immune therapies be helpful?
The chemotherapy drugs will cause a response early on and this may remove the lag phase in the beginning
What kind of biomarkers could be used for immune checkpoint therapies?
Tumour: - tumour mutation burden - PD-L1 immunohistochemistry - Microsatellite instability (MSI) - High Immune infiltrate in tumour - CD8 positive TIL score - Immunoscore - Immune gene expression signature
What is neoadjuvant therapy?
Having chemotherapy before surgery
What is adjuvant therapy?
Having chemotherapy after surgery
Who benefits from neoadjuvant and adjuvant therapies?
Patients who are MSI-high -ve
