hallmarks of cancer

Question 1

how do malignant tumours spread to other parts of the body

Answer 1

in the blood stream via angiogenesis

Question 2

hallmarks of cancer

mechanisms for acquiring the hallmarks

Answer 2

sustaining proliferative signalling ( activates cellular oncogenes)

evading groth suppressors ( inactive TP53)

avoiding immune destruction ( secrete TGFbeta)

enabling replicative immortality( switch on telomerase)

tumour promoting inflammation ( redirect inflammation promoting cells)

activating invasion and metastasis ( inactivate e-caherin)

inducing angiogenneis( induce VEGF)

genome instability and mutation ( inactivate DNA repair genes)

resting cell death ( produce IGF survival factor )

deregulation cellular energetics ( induce aerobic glycolysis)

Question 3

therapeutic targeting for hallmarks of cancer

Answer 3

EGFR inhibitors

cycle dependent kinase inhibrots

immune activation anti-CTLA4 mAb

telomerase inhibitors

selective anti-inflammatory drugs

inhibitors of HGF- met

inhibitors of VEGF signalling

PARP inhbiors

proapotpptic BH3 mimetics

aerobic glycolsosuis inhibitors

Question 4

malignant melanoma

Answer 4

BRAF most frequently mutated
MAP kinase pathway
other cancer include lung and colorectal
Hallmarks affected - ustained proliferative signalling and escaping programmed cell death are promoted by BRAF

Question 5

small cell lung cancer

Answer 5

TP53 most frequently mutated
Involved cell cycle arrest, apoptosis, senescence, DNA repair, changes in metabolism
Frequently mutated in ovarian colon and breast cancers
Li Fraumeni syndrome
Tp53 is involved in many of the hallmarks of cancer including evading growth suppressors, resisting cell death, genomic instability and deregulating cellular energetics
Mutant TP53 can impair apoptotic response, the G1 checkpoint and DNA repair mechanisms

Question 6

pancreas

Answer 6

KRAS most frequently mutated
RAS proteins are small GTPases which cycle. RAS proteins are central mediators downstream of growth factor receptor signalling and therefore are critical for cell proliferation, survival, and differentiation. PI3K and RAF pathways
Frequently mutated in colon, pancreas and lung
Evidence implicating mutated Kras in evading many of the hallmarks of cancer including sustained proliferative signalling and angiogenesis.
Mutations cause Ras to accumulate in the active GTP bound state by impairing intrinsic GTPase activity and conferring resistance to GTPase activating proteins

SMAD4

Question 7

Large intestine (right, carcinoma, adenocarcinoma)

Answer 7

APC
B-catenin/Wnt signalling pathway. APC binds b-catenin and targets it for degradation, in the presence of a Wnt signal complex is broken down and b-catenin travels to nucleus to help activate gene transcription
Cancers of colon, lung and prostate
Adenomatous polyposis coli and others
Mutant APC doesn’t bind b-catenin suppression of growth hallmark is affected
Inactivation also increases chances of chromosomal instability
Also roles in apoptosis and migration

Question 8

kidneys

Answer 8

VHL
Inhibitor of hypoxia induced transcription factors (HIF1) which stimulate hypoxia inducible genes such as VEGF
Also in lung, colon, bladder (and Phaeochromocytoma)
Von-Hippel Lindau syndrome
Hallmark affect by mutant VHL = induction of angiogenesis (possibly invasion and metastasis as well)
Also roles in invasion and metastasis, escaping programmed cell death etc