Cancer

Question 1

Describe how the immune system protects against cancer?

Answer 1

• Cancer cells present stress-associated molecules which are detected by NK cells. Dendritic cells also activate T cells which can detect tumour-associated antgens due to T cell receptor. NK and T cells then release perforin and granucytes which induce apoptosis
• Helper T cells can activate dendritic cells inorder to rectuir more Cytotoxic T cells, and also release cytokines such as TNF-gamma which encourages the recruitment of NK cells

Question 2

Describe how cancer can evade the immune system

Answer 2

• Express inhibitory molecules - cancer cells can express PDL1 which binds to PD1 receptor on T cells, inhibitign their immune response
• Can adapt to stop presenting recognisable proteins
• Can recruit other immune cells in or to suppress response - regulatory T cells and macrophages will be recruited and prevent the action of cytotoxic T cells

Question 3

what is BRAF and how does it cause cancer?

How can such cancer be treated?

Answer 3

A proto-oncogene, producing B-RAF protein which is involved in MAP kinase pathway of signal transduction to cause transcription

With a BRAF mutation, one of the messenger proteins in the MAPK pathway becomes constatnly switched on, meanin gthat despite counter-regulatory mechanisms, transcription constantly occurs - tumour development

Vemurafenic is a B-raf enzyme inhibitor, inducing apoptosis of a cell by interupting the BRAF-MEK step - only works if BRAF has V600E mutation

Question 4

Describe the metastatic cascade and for each identify a metastatic mechanism of action

Answer 4

• Local invasion - Decrease in ECD, differentiated integrins, Increase in CKs and HGF
• Neovasculaisation or Angiogenesis - VEGF increase
• Detachment
• Intravasation
• Transport - increase in uPA or MMPs
• Lodgement/arrest
• Extravasation - Differential of selectin or CD44 - selective adhesion
• Growthsite at ectopic site - decrease in angostatin and endostatin

Question 5

Describe properties of cancer which allow them to metastasise

Answer 5

• Reduced cell-cell adhesion by getting rid of E-cadherin either anti-Ecadherin antibodies, exon skipping resulting in no Calcium domain (E-cadherin is calcium mediated) or mtation in alpha and beta-catenin (help E-cadherin bind)
• Altered cell-substratum adhesion - integrins help bind to CAMs in other cells
• Increased motility - hepatocyte growth factor induces epithelial cells to dissociate and scatter by binding to c-met which leads to phosphorylation of Beta-cantenin
• Increased proteolytic ability through uPAs and MMPs
• Angiogenics ability - increase in VEGF. Blood vessels produced are weak and clots are common - perfect for metastatic growth
• ability to proliferate - soil and seed theory

Question 6

Describe how immunotherapy can be used in cancer treatment

Answer 6

• Cytotoxic T cell recruitment
• Cytokine therapy - IF-2 and IFN-alpha given to recruit NK, T and dendritic cells
• Antibodies which bind to PD1 on T cell prevent PDL1 binding to it - allows for T cell to work
• DCA4 when blocked drives dendritic cells to stimulate anti-cancer cell responses