CANCER Flashcards
Define neoplasm.
Uncontrolled cell growth
ie tumour
Define cancer.
Malignant neoplasm
Carcinomas are defined as…
Malignant epithelium neoplasms
Sarcomas are defined as…
Malignant mesenchymal neoplasms
What are adenocarcinomas?
Malignant epithelium neoplasms of glandular origin
What are adenomas?
Benign neoplasms of glandular origin
What are fibroadenomas?
Benign neoplasms of fibrous and glandular origin
Most benign neoplasms end with -oma except…
Lymphoma
Leukaemia
Hepatoma
Melanoma
Myeloma
What is teratoma?
A tumour with tissue or organ components resembling normal derivatives of more than one germ layer
What is a blastoma?
A type of cancer caused in malignant precursor cells
Describe 7 microscopic features of malignant tumours.
Hyperchromatic nuclei
High mitosis
High nucleo-cytoplasmic ratio
Pleomorphism
Irregular outline
Prominent nucleolus
Enlarged
How do you describe benign tissue?
Cells resemble normal tissue
Few mitosis
No invasion
Highly differentiated
What are the histopathological features of squamous cell carcinoma?
Keratin pearls
Pavementing
Intercellular bridges
What are the methods of cancer metastasis?
Local infiltration
Cavities
Lymphatic spread (Carcinomas)
Hematogenous spread (Sarcomas)
Based on what factors do you stage cancer?
T = Tumour size (T1-4)
M = Presence of distant metastasis (M0/1)
N = Presence of regional lymph node metastasis (N0-2)
What are the histopathological features of glandular cancers?
Mucin
What does T4 mean?
Invasion of other organs by tumours
What is the difference between N1 and N2?
N1 = 1-3 lymph nodes involved
N2 = 4 lymph nodes involved
What does Tis mean?
No infiltration past the basement membrane
How is stage III cancer diagnosed?
N1 required (involvement of 1-3 regional lymph nodes)
What are the different gradings of cancer?
Grade 1 = well differentiated (normal cells)
Grade 2 = moderately differentiated (resemble normal cells)
Grade 3 = poorly differentiated
How is stage IV cancer diagnosed?
M1 required (presence of distant metastasis)
List the 9 tumour markers and their associated cancers.
HCG - Trophoblastic/ Non-seminomatous testicular tumours
Calcitonin - Thyroid medullary carcinoma
Caltechoamines - Pheochromocytoma
AFP - Liver cancer
CEA - Colon cancer
Prostatic acid phosphatase - Prostate cancer
CA-125 - Ovarian cancer
CA-19-9 - Colon/ Pancreatic cancer
CA-15-3 - Breast cancer
What are the 10 hallmarks of cancer?
Established:
Growth signal autonomy
Evasion of inhibitory growth signals
Evasion of apoptosis
Unlimited replicative potential
Angiogenesis
Invasion & metastasis
Emerging:
Avoiding immune destruction
Reprogramming energy metabolism
Enabling characteristics:
Genome instability
Tumour-promoting inflammation
List the broad ways growth autonomy affects the cell.
Excessive production of growth factors w/o appropriate stimulus eg PDGF in glioblastomas
Growth factor receptor amplification eg HER2 in breast cancer
Growth factor receptor constitutive activation eg EGFR for lung adenocarcinoma
Signalling molecules activated without receptor eg mutated KRAS => constant MAPK signalling pathway activation => uncontrolled proliferation
Auto transcription by MYC producing proteins/factors that aid replication eg Burkitt lymphoma; starry sky appearance; IgH t(8:14) translocation
Name 2 tumour supression genes.
p53 and Retinoblastoma
How does p53 exert its effect?
Safeguards genomic stability
Cell cycle arrest
Cellular senescence
DNA repair
Apoptosis
Inhibit angiogenesis
What are the activators of p53?
Hypoxia
Damaged DNA
Inappropriate oncogene signalling
How does Retinoblastoma exert its effect?
Inhibits cell division (no apoptosis capabilities)
Acts on G1/S transition phase of cell cycle
How is Retinoblastoma inactivated by cancer cells?
Inactivated via hyperphosphorylation
Cancer gene amplification of cyclin D and CDK4 gene / mutate both Rb alleles
What is the intrinsic pathway of apoptosis?
DNA damage triggers p53
Upregulation of apoptotic factors BAX/BAK
Egression of cytochrome C & capase production
Apoptosis
How do tumour cells overcome intrinsic apoptosis pathways?
Upregulation of BCL2
Lose p53
What does TP53 mutation cause?
Li-Fraumeni syndrome
What gene is activated and what translocation occurs in follicular lymphoma?
BCL2 gene due to t(14,18) translocation in B cells
What allows for unlimited replicative potential in tumour cells?
Telomerase reactivation causing evasion of hayflick limit and divide infinitely
What are the anti-angiogenic factors?
p53 producing TSP-1
What are the pro-angiogenic factors?
PDGF
EGF
VEGF (from hypoxia producing HIF-a / oncogenes ras, myc)
How does invasion and metastasis occur?
Detachment of tumour cells by inactivating E-cadherin function
Mobilised by epithelial-mesenchymal transition
Breach basement membrane via secretion of proteolytic enzymes
Circulate as emboli => extravasate => angiogenesis
How do tumour cells evade immune destruction?
Downregulate MHC
Secrete inhibitory cytokines TGF-B
Engage inhibitory receptors PD1
Lose expression of tumour antigens
Promote Tregs
How do tumour cells reprogram energy metabolism?
Aerobic glycolysis
Lactic acid fermentation causes diversion of glycolytic intermediates, which enable synthesis of macromolecules and organelles for cell growth
How does genomic instability affect tumour cell?
Loss of MMR protein (eg MLH1) leads to high levels of macrosatellite instability causing the cell to be more prone to mutations
How does loss of MMR protein occur?
Gene deletion
LOF mutation
How does inflammation enhance tumours?
Inflammation provides growth factors, pro-angiogenic factors, ECM modifying enzymes
Name 2 classes of anti-cancer drugs.
Cell cycle specific and cell cycle non-specific
What are the 3 cell cycle specific drugs?
Anti-metabolites
Microtubule inhibitors
Topoisomerase I/II inhibitors
What are the 3 cell cycle non-specific drugs?
Alkylating agents
Platinating agents
Cytotoxic antibiotics
Name 2 anti-metabolite anti-cancer drugs and what they inhibit.
Methotrexate inhibits dihydrofolate reductase
5-flourouracil inhibits thymidylate synthase
Name 2 microtubule inhibitors and state their functions.
Vinblastine (binds polymerising ends preventing elongation)
Paclitaxel (stabilise microtubules prevents depolymerisation)
Name an alkylating agent and state its function.
Cyclophosphamide (Crosslink DNA and prevent transcription and translation)
Name 2 platinizing agents and state their functions.
Cisplatin and Carboplatin (Crosslink DNA and prevent transcription and translation)
Name 2 cytotoxic antibiotic anti-cancer drugs and state their functions.
Anthracyclie and Doxorucibin (crosslink and damage DNA)
What are the adverse effects of alkylating agents?
Haemorrhagic cystitis
What are the adverse effects of Platinating agents?
Nephro/Ototoxicity
What are the adverse effects of cytotoxic antibiotics?
Cardiotoxicity
What are the general adverse effects of anti-cancer drugs?
Alopecia
GI toxicity
Myelosupression
What is associated with Hodgkin’s lymphoma?
Reed-sternberg cells
What is an effective treatment for MMR deficient tumour cells with micro satellite instability?
Anti-PD1 therapy
