outline of disease process in cancer

Question 1

cancer cells

Answer 1

loss of contact inhibition

increase in growth factor secretion

increase in oncogene expression

loss of tumour suppression genes

frequent mitoses

Question 2

normal cells

Answer 2

intermittent/co-ordinated growth factor secretion oncogene expression is rare presence of tumour suppression genes few mitoses

Question 3

multistage carcinogenesis

Answer 3

carcinogen initiation pre-clinical: promotion, tumour growth clinical: progression

Question 4

spread of cancer is often in the …

Answer 4

lymphatic system can also be haematological

Question 5

tumour growth

Answer 5

cancers have different rates of growth but follow similar patterns detecting cancer in the early stages while still localised is ideal

Question 6

what are the 3 categories in causes of cancer growth

Answer 6

initiation promotion progression

Question 7

initiation causes

Answer 7

chemical, physical, viral

Question 8

promotion causes

Answer 8

oncognes growth factors

Question 9

progression causes

Answer 9

metastases

Question 10

chemical carcinogens

Answer 10

polycyclic hydrocarbons, soots and tars, aniline dyes (bladder cancer), aflatoxin (liver), nitrogen mustard (leukaemia), alcohol and smoking (lung, head and neck, GI)

Question 11

physical carcinogens

Answer 11

ionising radiation (dose-response relationship, radon source is mainly buildings, risk increased by smoking, ventilation reduces risk) e.g. Chernobyl residents displayed very unique and resistant tumours

Question 12

mechanisms by which physical carcinogens cause cancer

Answer 12

chromosome translocation, gene amplification, oncogene activation

Question 13

viral carcinogens

Answer 13

avian leukaemia, avian sarcoma herpes virus (Burkitt’s lymphoma) papillomavirus (cervical cancer) retrovirus (HTLV1 - adult T cell leukaemia/lymphoma HTLV2 - hairy cell leukaemia) hep B (liver)

Question 14

oncogenes

Answer 14

transforming genes, positive regulators of growth, represent a gain in function to transformed cells e.g. follicular lymphoma t(14:18) (q32; q21), BCL2 activation prevents apoptosis

Question 15

growth factors

Answer 15

polypeptide molecules, required by the body regulate growth and function, bind to cell membrane receptors, stimulate activation of intracellular signal transduction pathways

Question 16

metastasis

Answer 16

not random, cascade of limited sequential steps, involves tumour- host interactions, survival of the fittest pertains Tumour invades through BM, moves into ECM/connective tissue/surrounding cells, invades blood vessels, tumour cells arrested in distant organ

Question 17

autocrine stimulation

Answer 17

Cell carries receptor and secretes GF (two targets), cell escapes normal control mechanism

Question 18

paracrine stimulation

Answer 18

GF acting on a cell are produced locally by the cell or its immediate neighbours Produces growth in itself and neighbours, creates a micro-environment which allows for the successful formation of the tumour

Question 19

tumour suppressor genes

Answer 19

p53 - most commonly altered gene in human tumours (37% but higher in lung and colon); normal function is as a transcriptional regulator, promoted DNA repair (increased risk of mutations which go unchecked), apoptosis, differentiation (poorly differentiated tend to be more aggressive); induced by DNA damage and hypoxia; G1/S checkpoint control gene

Question 20

non-squamous cell lung cancer targets and therapy

Answer 20

molecular basis is determining treatment options focus not on where the cancer is

Question 21

angiogenesis

Answer 21

• Key process in maintenance and progression of malignant tumours - New blood vessels must form for a tumour mass to exceed 2mm diameter - Degradation of the ECM is necessary for new blood vessel formation to occur - Clinical correlations are seen between vessel density, tumour malignancy and metastasis Allows for blood-borne metastatic disease

Question 22

anti-VEGF antibody avastin

Answer 22

• Binds VEGF - Prevents ○ Interaction with receptors ○ Activation of downstream signalling pathways - Ultimately ○ Vascular regression ○ Tumour dormant - Anti-VEGF therapy normalises vasculature

Question 23

immune recognition of foreign cancer cells

Answer 23

Cancer cells can hide from T cells - they aren’t foreign cells so they are able to hide

PD1 present on T lymphocytes (programmed death receptor)

Ligand (PDL-1) on tumour cells

Interaction of these suppresses T cell action

Therapeutic opportunity to block PD1 or PDL-1

Question 24

explain the principles of staging in cancer

Answer 24

staging takes several factors into account in order to help assess local/distant spread, diagnose the patient and make a prognosis

position of the tumour

depth of penetration of the tumour

relationship to adjacent structures

involvement of regional lymph nodes

presence of distant metastases