Cancer Patho And Immunotherapy

Question 1

Common oncogenes mutated in blood/lymph cancers

Answer 1

FLT3 (point mutation)

PDGFRB (translocations)

KIT (point mutation)

ALK (translocations)

Question 2

ABL-BCR tyrosine kinase oncogene mutations

Answer 2

Commonly affected in CML and ALL cancer types

• caused by a translocation of chromosome 9-> chromosome 22 (t(9:22))*

This translocation causes a continuously active BCR_ABL tyrosine kinase

also know as the Philadelphia chromosome

Question 3

MYC oncogene mutations

Answer 3

Commonly mutated in Burkett’s lymphoma

Translocation of the C-MYC gene on chromosome 8 -> 14 (t(8:14))

Causes a continuous activation of MYC expression

Question 4

BCL2 gene mutations

Answer 4

Most commonly mutated in B-cell lymphomas

translocation from chromosome 14 -> 18
(T(14:18))

Causes over expression of BCL2 protein which protects lymphocytes and B-cells from apoptosis
- B-cells cancers want this so they don’t die

Question 5

Mechanisms which tumors evade immune system

Answer 5

Prevents tumor antigen presentation
- T cells cant recognize tumor

Mutations in MHC genes
- T cells can recognize tumor

Production of immunosuppressive proteins or expression of inhibitory cell surface proteins
- inhibition of T cell activation

Question 6

If you have little immune response, what cancer is most likely to occur

Answer 6

Lymphomas

Question 7

CTLA 4 checkpoint pathway

Answer 7

When the CTLA-4 molecule connects instead of other molecules and shuts down T-cell response/proliferation

• a check point mechanism*

Question 8

PD-1 checkpoint pathway

Answer 8

When PD-1 connects to PD-L1, T cell response/proliferation is shut down

• a checkpoint mechanism*

Question 9

Common MOAs of immunotherapies

Answer 9

Stimulate immunity to attack tumor (and some self)

Preventing or stopping immune.suppression mechanisms used by tumors cells

Question 10

BCG for bladder cancer immunotherapy

Answer 10

Attenuated bacteria that infects bladder cells of humans (including the tumor cells)

• death of cells caused by this bacteria causes immune system to now recognize tumor cells
• kills both tumor and host cells but more tumor cells.

Question 11

Anti cancer antibodies MOA

Answer 11

Exposes cancer cells to immune system via opsonination

Block cell growth and angiogenesis

Stops immune inhibition tactics

Directly is cytotoxic to select cancer species

• can engineer antibodies to recognize more than one cancer types/chemo drugs *

Question 12

Car-T therapy for cancer

Answer 12

Take patient cells out of blood

Put DNA in for a select marker in the cells

Proliferate cells and then inject back into patient

Cells now kill tumor

CD 3,4,8 = T cells ; CD18,19,20,21 = B cells

Question 13

Philadelphia chromsome

Answer 13

t(9:22) results in chimeric BCR-ABL tyrosine kinase