Cancer Flashcards
What are the 4 stages of a cells life cycle?
Stasis
Mitosis
Differentiation
Apoptosis
What is the abcd of melanoma growth
Asymmetry
Borders (uneven)
Colour
Diameter
A) What are the two main ways that mutations occur?
B) What usually happens to a damaged cell? (2)
C) Why do cancer cells not die?
A) replication errors (accumulate with age) and exposure to DNA damaging agents
B) cell will repair the damage, or die
C) cells have faulty repair or apoptosis genes
Give some examples of genes
A) in controlling cell growth
B) in DNA repair and genome stability
C) in controlling cell death
A) RAS, ABL, SRC, RB, MDM2
B) p53, telomerase, ATM, BRCA
C) Bcl-2 family genes, myc
What are oncogenes?
Mutant or normal copies of cellular genes
Control cell growth
Have the potential to cause cancer
What are anti-oncogenes?
Also called tumour suppressors
Genes whose function is lost in tumours either by deletion or null mutation or down regulation by miRNAs
What phenotype do oncogenes usually have?
Dominant
How are oncogenes activated? (3)
- Point mutation - May alter function of normal
- Over expression of normal gene product - gene amplification, translocation to transcription ally active site, reduced expression if controlling miRNA
- creation of a novel gene by translocation
What is a homogeneously staining region?
A type of change in a chromosomes structure which is frequently observed in the nucleus of human cancer cells, where a segment of the chromosome has been tandemly duplicated many times
They have various lengths and staining intensity after G banding
MiRNAs are a class of ______ RNA molecules. miRNA molecules bind to target ____ molecules and prevent ______ of the protein? miRNAs are known to regulate _______ expression. If a _____ that normally down regulates oncogene expression is itself down regulated then ______ of the oncogene will be translated.
MiRNAs are a class of regulatory RNA molecules. miRNA molecules bind to target mRNA molecules and prevent translation of the protein. miRNAs are known to regulate oncogene expression. If a miRNA that normally down regulates oncogene expression is itself down regulated then more of the oncogene will be translated.
miR-16-1 usually regulates ____ expression
miR-16-1 expression is reduced in ______, thus ____ expression of ___
miRNA of the let-7 family regulate _____ expression
Reduced expression is let-7 in lung tumours is associated with _____ expression of ______
miR-16-1 usually regulates Bcl-2 expression
miR-16-1 expression is reduced in chronic lymphocytic leukaemia and increases expression of Bcl-2
miRNA of the let-7 family regulate Ras expression
Reduced expression is let-7 in lung tumours is associated with increased_ expression of Ras
How is tumour suppressor activity lost? (6)
(Both alleles of gene need to be inactive) Point mutations Deletion (loss of heterozygosity) Methylation (= gene silencing) Down regulation by miRNAs Mitotic non disjunction Mitotic recombination (rare)
How can ts genes be silenced?
By epigenetic modifications of the DNA (eg. Methylation)
Over expression of miRNAs
Where and how are oncogenes found..
Often Located at translocation break points
Present in HSR or double minutes
Found by transducing retroviruses and identified as miRNA target
What are DNA double minutes?
Small fragments of extra chromosomal DNA which are a manifestation of gene amplification during the development of tumours which give the cells selective advantages for growth and survival
Ts genes: Region is \_\_\_\_\_\_ in tumour cells Loss of \_\_\_\_\_zygosity Mutated in \_\_\_\_\_\_\_\_\_ Identified as a \_\_\_\_\_\_\_\_\_
Ts genes: Region is deleted in tumour cells Loss of heterozygosity Mutated in familial cancer syndromes Identified as a miRNA
Write down the multistep process of normal cell -> metastasis
- Normal cell needs growth factor for growth and survival – no factor, cell differentiates or dies
- Cell becomes factor independent – can grow or differentiate when factor absent, but if cell cycle disrupted will die
- Cell becomes unresponsive to cell cycle control – cannot differentiate, can grow or die
- Cell becomes resistant to apoptosis – cell grows, cannot die
- Cell cannot repair damaged DNA – as it cannot die by apoptosis, damaged cells survive – tumour genetically unstable and mutations accumulate
- Cell loses contacts with surrounding cells – spreads to other sites
Give 2 familiar cancer syndromes that are specific to certain tissues
Give 2 familiar cancer syndromes that affect multiple tissues
Early onset Breast cancer (BRA2) Neurofibromatosis (NF1/2) --- Li-Fraumeni syndrome (p53) Ataxia telangiectasia (ATM)
Give 4 reasons that cancer mortality is still high
- Tumour is too advanced before diagnosis
- Tumour becomes resistant to treatment
- No effective treatment available for that tumour
- Opportunistic infections occur due to poor immune system.
What is the first line of defence against a tumour, give some disadvantages to this..
Surgical removal
Can be disabling or disfiguring, or may promote the spread of the tumour.
Chemotherapy -
give the effect of the following agent on DNA
and an example..
Alkylating agents -
Alkylating agents - Damages DNA. Used in treating blood cancers, lung, breast ovarian. e.g. cisplatin, chlorambucil.
Chemotherapy -
give the effect of the following agent on DNA
and an example..
Nitrosoureas
Nitrosoureas - Damages DNA, crosses blood-brain barrier. Used for brain tumours. e.g. Streptozocin
Chemotherapy -
give the effect of the following agent on DNA
and an example..
Antimetabolites
Antimetabolites - Targets cells in S phase and interferes with DNA and RNA synthesis.e.g. 5-fluorouracil, methotrexate.
Chemotherapy -
give the effect of the following agent on DNA
and an example..
Anthracyclines -
Anthracyclines - interferes with enzymes involved in replication e.g. doxorubicin.
Chemotherapy -
give the effect of the following agent on DNA
and an example..
Topoisomerase inhibitors -
Topoisomerase inhibitors - Interferes with accurate DNA replication e.g. etoposide
Chemotherapy -
give the effect of the following agent on DNA
and an example..
Mitotic inhibitors -
Mitotic inhibitors - Block mitosis M phase e.g. paclitaxel, vinblastine
What role do corticosteroids play in chemotherapy?
Corticosteroids - commonly used as anti-emetics to help prevent nausea and vomiting caused by chemotherapy
Give 3 problems with chemotherapy
1) The side effects - damages any fast growing cells
2) Tumours develop resistance to drugs
3) Some tissues are hard to target (may have reduced efficacy by time it reaches tumour OR blood-brain barrier)
What are immunomodulatory drugs?
Boost the body’s own immune system to help attack the tumour
(Novel cancer therapies) What is:
used to treat CML and GIST (GI stromal tumour). Inhibits tyrosine kinase ( a novel TK is produced by the Brc-Abl translocation in CML)
Glivec
(Novel cancer therapies) What is:
a new therapy to treat non small cell lung cancer – blocks the epidermal growth factor receptor (EGFr)
In trial – Iressa
(Novel cancer therapies) What is:
used in advanced pancreatic cancer, blocks EGFr
Tarceva
(Novel cancer therapies) What is:
used in advanced pancreatic cancer, blocks EGFr
Tarceva
What is the antibody that binds to the Her2 antigen that is expressed on a subset of breast cancers that is used in cancer treatment.
Herceptin
What is the antibody that binds to the Her2 antigen that is expressed on a subset of breast cancers
Herceptin
What exploits the DNA repair deficit in BRCA positive breast cancer cells leading to irreparable double strand breaks, used in cancer treatment.
Olaparib
