Cancer Flashcards
What happens to proto-oncogenes to make them oncogenes?
They get a gain of function - enhanced kinase activity, uncontrolled signalling for example
What is HER2?
Receptor tyrosine-protein kinase
How does retinoblastoma protein normally prevent cell cycle progression?
pRb normally stops the cells ability to progress from G1 to S stage. When cell ready to divide pRb is phosphorylated, inactivating it, allowing cell cycle to progress
What does p21 do?
it becomes activated when p53 is phosphorylated.
When active it inhibits CDK which leads to cell cycle arrest
What does loss of BRCA1/2 result in?
Results in strand breaks and aneeuploidy
What is the main role of BRCA2?
Regulating the function of RAD51 in repair by homologous recombination at G2/M checkpoint
(BRCA1 has broader role upstream)
How can Bcl-2 play a role in leukaemia/lymphoma?
Overexpression of BCL2 may prevent cell death in cancer cells
What does imatinib work on?
The bcr-abl part of the phildedelphia chromosome (due to the 9,22 translocation)
What is the BRAF-V6OOE mutation common in?
Melanoma
When would EGFR inhibitors not work?
When KRAS is also mutated
What is a drug for breast cancer that can be directed into the lysosome?
Trastuzumab emtansine
What cancer does trastuzumab target ?
Breast and stomah cancer that is HER2 positive
What payload is carried by trastuzumab emtansine and what does it do?
DM1 - microtubule inhibitor. It is directed into lysosome
what is a dangerous side effect of Trastuzumab?
Cardiotoxicity (As the HER2 surivival pathways seem to be cardiac protective)
What are the two most common mutations in pancreatic cancer?
K-ras (90%)
P53 (50%)
Where do pancreatic cancers tend to arise?
exocrine pancreas - ductal adenocarcinomas
What is a common pancreatic cancer presentation>
Obstructive weight loss associated with weight loss,
epigastric pain radiating through to back
What blood biomarker is often raised in ovarian cancer?
CA-125
What chemo is often used in ovarian cancer?
Platinum + a taxane
What happens in myeloma?
You get unregulated proliferation of monoclonal plasma cells in the bone marrow
How does myeloma present?
CRAB
Calcium high
Renal failure
Anaemia
Bone pain due to lytic bone lesions
What can gamma knife treat?
Things in the brain needing radiotherapy
What are some acute side effects of radiotherapy?
Skin reaction, fatigue, pain, pruritus
What are the most common breast cancer genes?
BRCA1
BRCA2
TP53
CHEK2
What type of cancers do breast cancers tend to be?
Adenocarcinomas
What receptor in breast cancer often has a better prognosis?
oestrogen receptor
What is a smooth lump in the breast that moves easily likely to be?
Fibroadenoma - benign breast condition
What cells do acute lymphocytic leukemia arise from?
Lymphoid progenitor cells
What cells do chronic lymphocytic leukemia arise from?
B cells
What cells does acute myelogenous leukemia arise from?
Myeloid progenitor cells
What does polatuzumab vedotin treat?
B cell lymphoma
It is a CD79b directed antibody drug conjugate
(lara polat loves CDs from 1979)
What germline mutations get regular colorectal cancer screening from a young age?
APC or MLH1/MSH2
What appearance do small cell carcinomas have on a biopsy?
Salt and pepper chromatin appearance under H&E
Name the non-small cell carcinomas?
Adenocarcinoma, squamous cell carcinoma, large cell carcinoma
In what lung carcinoma do you see keratin pearls?
Squamous cell carcinoma
What gene can be mutated in squamous cell carcinoma?
FGFR1 (Fibroblast growth factor receptor 1)
How do the adenocarcinomas (lung cancer) arise?
Gain of function mutations in growth factor signalling pathways (eg receptor tyrosine kinases)
What lung cancer is the most common in non smokers?
Adenocarcinoma
How do platinum agents work?
Through the development of covalent adducts preventing replication
(all end in platin carboplatin, cisplatin etc)
How do the anti-metabolites work?
They are all structural analogs of molecules normally involved in cell growth eg methotrexate is a deriv of folic acid. (S phase)
How do the vinca alkaloids work? (vinblastine, vincristine)
They prevent the assembly of microtubules and inhibit spindle formation
How does actinomycin-D work?
Cytotoxic effects by intercalation between guanine-cytosine base bairs with inhibition of synthesis of RNA
How does L-asparaginase work as a chemo agent?
It depletes asparagine in blood stream which deprives tumour cells of required amino acids and inhibits protein synthesis (from E Coli)
How does Trabectedin work?
Binds to the minor groove of DNA bending helix towards major groove?
What is a common side effect of bleomycin?
Flagellate erythema (rash) and pulmonary fibrosis
What is a side effect of doxorubicin?
Raspberry urine
What is a side effect of capecitabine?
Palmar-planter erythrodysesthesia (hand foot syndrome)
What is a side effect of Imantinib? (tyrosine kinase inhibitor)
peri-orbital oedema
Whereabouts do the majority of prostate cancers arise from?
peripheral zone (less likely to cause urinary symptoms)
What medication can be used to treat prostate cancer?
LHRH antagonist (causes testicles to stop making testosterone)
What does TMN system refer to?
T= size of cancer 1-4
N= lymph node status 0-3
M= metastasis M0 = no distant spread, M1 has spread to distant organs
What do the prefixes to the TMN staging mean?
p=pathological stage
c=clinal stage
y=restaged after therapy
r = restaged after recurrence
What is Duke’s classification a staging for?
Colorectal cancer
Where does breast cancer often metastise to?
Brain
What is downregulated in metastatic breast cancer?
E-cadherin and BRCA1
What is the difference between carcinoma and sarcoma?
Carcinoma = epithelial
Sarcoma = mesenchymal
What is the name for a benign and malignant tumour of neuroectoderm origin?
Naevus = benign
Melanoma = malignant
Where are myoxomas and myxosarcomas from?
Embryonic fibrous tissue
What’s the benign and malignant name of tumours of nerve cells?
Benign = ganglioneuroma, malignant = neuroblastoma
At what age is red reflex checked in babies?
newborn and 6 weeks
When does breast cancer screening take place and how long for?
50-70 every 3 years
When is bowel screening done?
50-74 every 2 years
What is one of the most common side effects of radiotherapy?
Skin reaction and itching
What are the three occult cancers?
Myeloma, ovarian and panceatic
What epigenetic modification in tumour suppressor genes results in a loss of gene expression?
Hypermethylation
When is cervical cancer screened for?
25-49 every 3 years. 50-64 5 yearly
What does cancer grading take into account?
1) degree of anaplasia
2) rate of growth
eg grade 1 is less than 25% anaplastic cells
grade 4 is more than 75%
What does intravastation refer to?
invasion of cancer cells through basement membrane to blood vessles
What is often upregulated in metastatic breast cancer?
VEGF
What does R0 refer to?
the complete removal of all tissue containing tumour with a margin of intact unaffected tissue
What are the only identified gene mutations linked to prostate cancer?
BRCA1 and BRCA2
Would a Gleason score of 6 be good or bad?
it means low grade, small and slow-growing
What is the name for radiation that comes in of seeds, ribbons, or wires?
Brachytherapy
What is a mechanism of treating metastatic prostate cancer?
medical castration through a LHRH agonist/antagonist
Difference between adjuvant and neo adjuvant?
neo-adjuvant given prior to surgery
adjuvant given after surgery
What chemo agents work on S phase?
methotrexate, 6-mercaptopurine and 5-flurouricil
What drugs work on the M phase?
The tubulin-active agents-
vinblastine, vincristine
and the taxanes - paclitaxel, docetaxel
How do cyclophosphamide, ifosfamide and busulfan work?
they are alkylating agents - add an alkyl group to DNA
What are irinotecan, topotecan and doxorubicin examples of?
Topoisomerase inhibitors. They block Topoisomerase which normally plays important roles in cellular reproduction and DNA organization
What type of cancer is small cell carcinoma?
neuroendocrine
What genes are involved in small cell lung cancer?
loss of tp53 and RB
amplification of MYC
What cancer would you use prophylactic cranial irradiation in?
small cell lung cancer
What is the inheritance patterns of the mutations in familial adenomatous polyposis and lynch syndrome?
autosomal dominant
What type of cancer are most colorectal cancers?
adenocarcinoma
Which type of stage 4 colorectal cancers respond well to immunotherapy with PD1 inhibitors?
MSI tumours - microsatelite instable
How do bispecific t-cell engagers work?
They bind to cancer cell antigen (cd20) and the cytotoxic t cells to get them to engage (cd3), then release cytotoxic granules
What are pembrolizumab, ipilumumab and retalimab examples of?
checkpoint inhibitors
What do HPV viral proteins E6 and E7 have high affinity for?
p53 and RB, inhibiting them
What receptors in breast cancer affect prognosis and how?
Estrogen receptor positive - better prognosis
Her2 positive - more aggressive
When is it most common to be triple negative in breast cancer?
more common in pre-menopause and BRCA1 (sensitive to early relapse
What is one gray?
one gray is the deposit of one joule of energy in one kg of matter
What does Whipples procedure treat?
pancreatic cancer
What translocation is common in myeloma?
IgVH
How can myeloma be screened for?
through serum protein electrophoresis - will see a monoclonal band
What is a benefit of small molecule kinase inhibitors over antibodies?
small molecule kinase inhibitors can be taken orally and also bind to a wider range of targets
What is trastuzumab dereuxtecan used to treat?
HER2 positive unresectable breast cancer. It is a third line therapy after trying trastuzumab- emantansine
What payload does trastuzumab deruxtecan carry?
topoisomerase I inhibitor (DXd payload)
What is Tarceva and what is it used for?
It is a small molecule tyrosine kinase inhibitor that works by steric hinderance of ATP binding pocket and it is used for metastatic non small cell lung cancer
What are side effects of therapies targeting EGFR?
slow wound healing and skin rashes
What does p53 do?
Its a transcription factor which increases expression of p21 (cyclin dependent kinase inhibitors)
Why can TERT upregulation lead to cancer?
Bc it maintains telomeres so allows cells that would otherwise undergo cell death to become immortal
How does pertuzumab work?
It inhibits ligand dependent HER2-HER3 dimerization and reduce signalling via intracellular pathways
