ls6003 solid cancer therapy (dr Modjthedi) Flashcards by Max Mordente

list 7 aetiological factors influcencing cancer

age
radiationchemicals
genetic dispostiion
ciruses and bacteria
dietary factors
immunosuppresion

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what do carcinogens do/

cause genetic alterations and DNA damage leading to cancer

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what are the 3 large groups of genes altered by carcinogens?

protooncogenes
tumour suppression genes
DNA repair genes

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what are the function and what effect does carcinogenisis have on proto-oncogenes, tumour suppression genes, DNA repair genes

proto-oncogenes= promote cell division / function become enhanced
tumour suppression genes=code for cell division suppression / funciton loss
DNA repair genes = code for DNA repair before cell devisio/ accelerate accumulation of mutated tumour suppresor genes and proto-genes

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Give examples for proto-oncogenes, tumour suppression genes, DNA repair genes

proto-oncogenes = Ras gene
tumour suppression gene = P53
DNA repair genes = ATM gene

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name 6 common genetic alteration types

point mutation - Kras
gene amplification - HER2
epigenetic alterations - gene silencing, DNA methylation
genetic alteration due to insertion/deletion
exogenous sequences - viruses such as HPV, EBV
chromosomal transloction/changes - Ph chromosome

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Oncogenes can be activate by 3 pathways, briefly describe these

A) mutation the DNA -> enhanced activity
B) Amplification results in increased amounts of normal protein
C) Translocation of part of DNA from one chromosomal location to another can produce a fusion protein

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Define the tumour types
Neoplasm/tumour -
Cancerous:
carcinoma -
sarcoma -
Lymphoma (leukaemia) -

-abnomral mass of tissue
-from endo/ectodermal i.e forms in the skin or tissue cells
- from mesdermal connective tissues e.g. bone, cartilage, also poorly differentiated
- cancers of hamopoietic system
(over 80% of cancers are carcinomas)

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cancers begin with accumulation of multiple mutatuions leading to genetic instability -> metastasis.
describe the general timeline for this

mutation inactivates tumour suppressor gene -> cells proliferate -> mutations inacrivate DNA reapir genes -> proto-oncogenes mutate to oncogenes -> more mutation, more genetic instability metatstatic disease (malignant tumour has broken through to blood vessels)

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describe benign

rare, non-invasive, never metastasise, prognosis (likelyhood of survial) is very good

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descrbe malignant

common on skin, invasive, often metastasize, prognosis is poor

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list the 5 stages of tumour development

cells with genetic mutation
hyperplasia (increase in the number of cells in an organ or tissue that appear normal under a microscope)
dysplasia (change in organisation of cells)
carcinoma in situ
invasive cancer

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list 7 hallmarks of cancer

uncontrolled proliferation
resistanc eot apoptosis
imoortaility
increased angiogenisis
invasion and metastasis
reprogramming of energy metabolisms
evastion of immune system
Tumor heterogeneity is one of the hallmarks of malignancy.

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list some of the common metastatic sites for prmiary tumours

prostate
colorectal
breast
melanoma
neuroblastoma

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what does stage 3 mean?

tumour has speead to lymph nodes

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what factors are responsible for cancer morbidity/mortality

metastasis
ruptures in vessels
compression of vital organs
infection
organ failure
starvation

3 approaches to fight cancer

A) prevention
B) early detection
C) treatment

4 possible outcomes for treatment

complete response (CR)
partial (PR)
STABLE DISEASE (SD)
Progessive disease (PD)

name 3 plainum based drugs

carboplatin
cisplatin
oxaliplatin

give 5 characteristic of cytotoxic anti-cancer drugs

-disrupt bio processes essential for cell division
-not specific for cancer cells. (kills non-target cells)
-work best on cells in S+M phase of cell cycle, not G1 though
-typically used in combination with agents which act at different cell cycle phases
-often administered in cycles to allow for tissue recovery

most cytotoxic drugs act at specific phases of cell cycle
what cllases act on M phase

Vinca alkaloids
taxanes

most cytotoxic drugs act at specific phases of cell cycle
what classes work at S phase

Methrotrexate (antimetabolite)
Hydoxyurea
cytosine arabinoside (Ara-C) (purine antagonist)
Anthracyclines ( e.g. doxorubicin)

most cytotoxic drugs act at specific phases of cell cycle
which are non-phase specific? i.e kill. both non-dividing and actively dividing cells

Alkylating agents (e.g bleomycin, carboplatin, cyclophosphamide)
Cisplatin
Nitrosoureas (Nitrosourea is both the name of a molecule, and a class of compounds that include a nitroso (R-NO) group and a urea) e.g. Streptozocin (Streptozotocin)
Antibiotics

most cytotoxic drugs act at specific phases of cell cycle, what is the advantage of using a combination therpay, attacking at different stages

allows for lower dosage, resulting in lower toxicity and a higher efficacy for treatment

what are the 3 clinical settings in which cytotoxic drugs are administered?

1) neoadjuvant (primary therapy prior to surgery, prevent metastasis) 2) adjuvant (after surgery/radiotherapy, reduce risk of relapse) 3) palliative care, improve patients QoL, palliaiting pain/symptoms

what factors effect efficacy of cytotoxic drugs?

total dose of drug reaching tumour duration of exposure proliferation fraction of tumour tumour size

give 4 examles of antimetabolites used to treat cancer

methotrexate doxorubicin paclitaxel irinotecan

give 2 limitiations of anticancer drugs used in chemo

1)toxicity 2)development of resistance to drugs

give 3 ways of reducing limitations surrounding anticancers drugs

-effective dosing and schedule -combination therapy + differrent therapuetic apporaches (radiotherapy) -supporting drugs

list some of the symptoms from drug toxicity

-anaemia, neutropenia (low number of white blood cells), thromboctopenia (platelet count in your blood is too low) -diarrehea, infertility, hair loss -nausea and vomiting

what are the 2 types of drug resistance?

primary (cancer does not respond to an immunotherapy strategy) acquired (clinical scenario in which a cancer initially responded to immunotherapy but after a period of time it relapsed and progressed(

what are 2 potentioal mechanims of drug resistance

1) inadequate drug exposure 2) alteration in cancer cell itself

try to list 8 otehr factors associated with drug resistance

-slower cell cycle time -geneitic instability -> high mutation rate -expression of resistant phenotype prior to chemotherapy -acquisition of additional genetic alterations folowing exposure to drug(secondary drug resistance) -increased capacity for DNA repairs -delivery of suboptimal dose due to poor tumour vasuclature i.e hypoxia -EMT - mesenchymal cells are more resisant to chemo than epithelial -presence of chemoresistance cancer stem cells

define epithelial-to-mesenchymal transition (EMT)

involved in tumor progression with metastatic expansion, and the generation of tumor cells with stem cell properties that play a major role in resistance to cancer treatment

name 4 strategies to overcome drug-resistance

-develop drugs that modulate/reverse resistance phenotypes -moleular profiling, discovery and targeting of more cancer specific drug-resistant antigens -combination therapy -development of smarter drugs with novel MoA: mAbs, TKIs

factors when designing combination therapy

-non-overlapping toxicity -optimal dose anad ferquency -non-overlapping mechanisms of drug resistance

whats FOLFOX?

common combination therpay for advanced colorectal cancer side effects: increased risk of infection, anaemia, bleeding, fatigue, nausea, pain

name 3 factors effecting survival rate of cancer patients

-tumour grade -cancer stage -tumour type