Lecture 19 -Basic Molecular Pathology Flashcards
How can a tumour biopsy be obtained for a central lung tumour?
How can a tumour biopsy be obtained for a peripheral lung tumour?
Central = Brochoscope
Peripheral = anaesthetic + needle through chest guided by ultrasound
What type of scan can be given to se if a malignancy has spread
PET scan
Positron Emission Tomography
What is gland forming cancer?
Adenocarcinoma
How do you confirm diagnosis of Non Small Cell Carcinoma?
Molecular markers
What are lung molecular markers for Lung Adenocarcinoma?
EGFR
Ros1
ALK
Kras
BRAF
MET
PET
PDL1
What lung molecular markers are raised in Lung adenocarcinoma in NON SMOKERS?
EGFR
Ros1
ALK
What lung adenocarcinoma marker is elevated in SMOKERs?
Kras
What type of molecules are the lung molecular markers?
Oncogenes
What is the only marker tested in squamous cell carcinoma?
PDL1
What ethnicity is the mutation of the EGFR oncogene most common in as a lung molecular marker?
Asian
What is the most frequent mutation causing the oncogene EGFR to be present as a lung molecular marker?
Deletion in Exon 19 of Ch7
What happens as a result of EGFR oncogene being present as a lung molecular marker?
It results in cell differentiation and proliferation, angiogenesis etc..
What chemotherapeutic drug can be given to treat patients with lung adenocarcinoma that have the EGFR lung molecular marker present?
What type of drug is this?
Why does this work?
Gefitinib
An anti EGFR TKI (Tyrosine Kinase Inhibitor)
EGFR is a Receptor Tyrosine Kinase
What is the downside to using Gefitinib to treat Adenocarcinoma of lungs with EGFR present?
Drug resistance
What is a lung molecular marker that is commonly seen in young never smokers that is an insulin receptor subfamily of RTK?
ALK
What does ALK do as an oncogene?
Signals cell proliferation and survival
What drug can be used to treat lung carcinoma with the lung marker ALK present?
What type of drug is this?
What is the worry/downside of this drug?
Crizotinib
ATP kinase inhibitor
Drug resistance
If a lung adenocarcinoma is positive for ROS1 molecular marker, what drug can be used?
What other molecular marker is this drug used for?
Crizotinib
ALK
What is the main molecular marker seen in lung adenocarcinoma of smokers?
KRAS
What is mutated in a lung adenocarcinoma with the molecular marker BRAF?
V600E mutation
What type of drugs can be used to treat lung adenocarcinoma with BRAF present?
What are 2 examples of these drugs?
Anti BRAF drugs
Dabrafenib and Trametinib
What are the Tumour Suppressor gene mutations that are common to Small cell carcinoma?
RB1 and myc mutation
What is a tumour suppressor that is commonly mutated in both small cell and non-squamous cell carcinoma?
p53 mutations
How do Tumour Cells use PDL1/PD1 to their advantage?
They use it to evade the immune response
Tumour cells make
PDL1 (Programmed Death Ligand 1)
PDL1 binds to the PD1 receptors on the T cells NOT allowing the T cells to recognise the cancer cell
What immunotherapy drugs act against the PD1 receptor on the T cells preventing PDL1 from binding preventing it from suppressing T cells action against cancer cells?
Nivolumab or Pembrolizumab
What immunotherapy drugs act against the PDL1 ligand, so nothing can bind to the PD1 receptor?
Atezolizumab and Duralumba
What is the problem with using Nivolumab/Pembrolizumab (against PD1 receptor) or Atezolizumab and Duralumba (against PDL1 ligand) as an immunotherapy against cancers?
Unable to predict treatment efficacy and side effects
What are some examples of growth factors produced by cancers?
PDGF (Platelet derived growth factor) - angiogenesis, stromal proliferation
TGF beta (transforming growth factor) - angiogenesis , interaction with lymphocytes and macrophages
What is EGFR?
Where is it expressed?
What condition is it over expressed in?
Tyrosine kinase receptor which is a growth factor receptor
Epithelial cells
Amplified and overexpressed in lung squamous cell carcinoma, Adenocarcinoma and breast cancer
What are some anti EGFR drugs?
Afatinib
Gefitinib
Erlotinib
What is a lobectomy of the lung?
Diseased lobe of the lung is removed
Histologically, how does a melanoma appear?
Brown cells
Pleomorphism
Increased nuclear to cytoplasmic ratio
Mitoses
What molecular marker is looked for in melanoma?
BRAF (V600E mutation)
What is a mutated V600E gene and affected lymph node indicative of?
Stage IV melanoma
What pathway gets activated in melanoma as a result of BRAF present?
Activation of MAPK (Mitogen Activated protein pathway)
What are 2 systemic therapies of melanoma:
Target therapy?
Immunotherapy?
Target therapy = anti BRAF (very good)
Immunotherapy = PDL1 target
What are 2 anti BRAF drugs that can be used as a target systemic therapy for melanoma?
Dabrafenib
Trametinib
What is the downside to only using Dabrafenib or Trametinib to treat a melanoma?
Tumour resistance can develop on selective BRAF inhibitors when they’re alone
What type of treatment is the first line treatment in patients with stage IV melanoma who are lacking BRAF mutations?
What drugs can be used for this?
How do they work?
Immunotherapy
Nivolumab
Pembrolizumab
Blocks the PD1 receptor preventing PDL1 from binding to it. This prevents PDL1 from preventing T cells from recognising cancer cells
What mutations are targeted in Metastatic urothelial carcinoma?
PDL1
What mutations are targeted in Head and Neck cancer metastasis?
PDL1
What mutations are targeted in Colorectal cancer?
DNA mis match repair enzymes
