Genes Implicated in Cancer Development

Question 1

Angiogenesis

Answer 1

Angiogenesis is the formation of new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells.

Question 2

Understand the hall marks of cancer.

Answer 2

Question 3

Production of IGF survival factors aids cancers in what way?

Answer 3

Evading apoptosis

Question 4

Understand

Answer 4

Question 5

Summarise the way in which cancer cells acquire the capability to sustain proliferative signalling.

Answer 5

Autocrine - production of growth factors

Paracrine - paracrine production of growth factors

Up-regulation of growth factor receptor proteins

Cancer cells can activate components of signalling pathway downstream from receptors, obviating the need to stimulate these receptors with GF ligand (K-Ras and B-RAF mutations)

Question 6

TP53 and pRB are examples of what genes?

Answer 6

Tumour suppressor genes

Question 7

Through what ways do cancer cells evade growth supressors (e.g pRB and TP53)?

Answer 7

Down-regulation or mutation of TGFb receptors, mutations in CDKs, deletion of CDK (cyclin dependant kinase) inhibitors and Rb inactivation are used to evade growth supressors.

Question 8

TGF-beta

Answer 8

Transforming growth factor beta

Question 9

How do cancer cells evade apoptosis, thus resisting cell death?

Answer 9

Most common is the loss of TP53 tumour suppression function.

Cancer cells can increase the expression of anti-apoptotic regulators such as Bcl-2 and Bcl-XL or of survival signals such as Igf1/2.

Cancer cells can down-regulate pro-apoptotic factors such as Bax, Bim and Puma.

Cancer cells can produce survival factors (e.g. IGF).

Cancer cells can produce a non-signalling decoy receptor for death ligand (FAS).

Question 10

Bcl-2 and Bcl XL act as what proteins?

Answer 10

Anti-apoptopic regulators.

Question 11

What telomerase enzyme do?

Answer 11

Telomerase is an enzyme (specialised DNA polymerase) that adds telomere repeat segments to the ends of telomeric DNA.

Question 12

What involvement do telomeres have in DNA?

Answer 12

Telomeres, composed of multiple tandem hexanucleotide repeats that protect the ends of chromosomes and are centrally involved in the capability of unlimited proliferation.

Question 13

How do cancer cells enable replicative immortality?

Answer 13

High expression of telomerase - which eliminates shortening of the telomeres.

Question 14

Summarise the steps of angiogenesis.

Answer 14

Question 15

VEGF

Answer 15

Vascular endothelial growth factor - expressed by tumours to stimulate angiogenesis.

Question 16

Metastasis

Answer 16

Metastasis is the development of secondary malignant growths at a distant site from a primary site of cancer and is responsible for ~90% of human cancer deaths.

Question 17

How P53 involved in angiogenesis?

Answer 17

A mutation in P53 results in down regulation of thrombospondin-1.

Thrombospondin is anti-angiogenic

Question 18

What is often seen inactivated in cases of metastasis?

Answer 18

Inactivation of E-cadherin - E-cadherin helps hold cells together so it’s inactivation helps give cancer cells the motility they need to metastasise.

Question 19

Define a driver mutation

Answer 19

A driver mutation confers growth advantage on the cancer cell and has been positively selected in the microenvironment of the tissue in which the cancer arises and is causally implicated in oncogenesis.

Question 20

Define a passenger mutation

Answer 20

A passenger mutation has not been selected, has not conferred clonal growth advantage and has not therefore contributed to cancer development.

Question 22

Proto-oncogene

Answer 22

Proto-oncogene: A normal gene which, when altered by mutation, becomes an oncogene that can contribute to cancer.

Question 23

What is the most frequent K-Ras mutation in human cancers?

Answer 23

The most frequent K-Ras mutation in human cancers is K-RasG12V

Question 24

What is Cetuximab and what is it used to treat?

Answer 24

Cetuximab is an EGFR inhibitor- blocks K-Ras.

Cetuximab is an EGFR inhibitor

Question 25

What is Knudson’s two hit hypothesis?

Answer 25

The Knudson hypothesis, also known as the two-hit hypothesis, is the hypothesis that most genes require two mutations to cause a phenotypic change.