Hormonal therapy 2

Question 1

7How does CDk4/6 inhibitors work?

Answer 1

Block phosphorylation of Rb, leads to G1 arrest.
This decreases the appearance of resistance to hormonal chemotherapy

Question 2

List examples of CDK4/6 inhibitors

Answer 2

Ribociclib
Palbociclib

Question 3

State the treatment options for prostate cancer

Answer 3

Watchful waiting
Active surveillance
Surgery
Hormonal therapy
Chemotherapy
Radiotherapy

Question 4

List the first two strategies used in Prostate cancer treatment

Answer 4

Androgen Deprivation Therapy (ADT)
Orchidectomy

GnRH agonist

Combined Androgen Blockade
GnRH agonist
Antiandrogen

Question 5

State additive hormonal manipulation in Prostate cancer

Answer 5

Additive hormonal manipulation
GnRH agonists - to inhibit release of LH/FSH

Blocks/down regulates pituitary receptors
After 7 days flare and bone pain disappears
Combo therapy with antiandrogens (cyperotone acetate)
Goserelin, buserelin, leuprorelin etc

Question 6

Facts about GNRH antagonists used in Prostate cancer

Answer 6

Competitive inhibition of GnRH binding such as

Cetrorelix, dagarelix

Question 7

Facts about antiandrogens used in Prostate cancer

Answer 7

inhibit the DHT-receptor complex formation eg flutamide, cyproterone, bicalutamide
Bone pain and tumour size are reduced
Gynaemastia an issue

Question 8

Enzalutamide is an antiandrogen used in Prostate cancer in later stage and its more effective than Bicalutamide. True/false?

Answer 8

True

Question 9

State the role of Abiraterone

Answer 9

blocks endogenous androgen production by inhibiting CYP17A1 (P450)

Question 10

State how finasteride work in Prostate cancer

Answer 10

Block the 5-alpha reductase enzyme
Converts testosterone to DHT

Question 11

Mrs T, a 39-year old woman, has been diagnosed with ER +ve, HER2 -ve advanced breast cancer and is being treated with an aromatase inhibitor and a LHRH antagonist. The aromatase inhibitor blocks the conversion of androgens to oestrogens to suppress the stimulus for tumour growth is called?

Answer 11

Anastrazole

Question 12

CDK4/6 form a complex with X which, when activated by oestrogen receptor, leads to progression through the cell cycle.

Answer 12

Cyclin D

Question 13

Ribociclib binds to the Cyclin D:CDK4/6 complex, blocking the phosphorylation and inhibition of X which leads to cell cycle arrest.

Answer 13

pRB

Question 14

Mr E, a 55 year old man, visited the Urology clinic, and following a biopsy a Gleason grade 6 prostate tumour was diagnosed. Mr E was treated with X as part of a combined androgen blockade (CAB) treatment functioning as an androgen receptor antagonist.

Answer 14

Bicalutamide

Question 15

RITUXIMAB is a biological agent that binds to….

Answer 15

CD20 on Bcells and makes them visible

Question 16

RITUXIMAB is used to treat….

Answer 16

Lymphomas and Leukaemia

Question 17

State the three mechanisms of action of RITUXIMAB

Answer 17

1. Complement mediated toxicity
   2.Antibody dependent cell mediated toxicity
2. Activation of caspases and apoptosis

Question 18

What is CTLA-4 ?

Answer 18

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation

Question 19

State the mechanism of action of Ipilimumab

Answer 19

Ipilimumab is a monoclonal antibody that binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86

Question 20

Ipilimumab is used to treat…

Answer 20

Ipilimumab approved for melanoma and renal tumours but significant side effects such as skin rash

Question 21

What drug has a better treatment profile than Ipilimumab?

Answer 21

PD-1/PD-L1 inhibitors

Question 22

List examples of PD-1/PD-L1 inhibitors?

Answer 22

Pembrolizumab and Nivolumab

Question 23

State how immunotherapy such as pembrolizumab works

Answer 23

Either bind to PD-1 or PD-L1
Tumour cell now no longer ‘hidden’ from the immune response

Question 24

What is the Current first-line treatment decisions for advanced NSCLC are based on the presence of genetic aberrations?
Sensitizing mutations EGFR
Translocations of ALK.

Answer 24

Pembrolizumab/Nivolumab

Question 25

What is CAR-T cell therapy?

Answer 25

CAR-T cell therapy involves using engineered T cells expressing tumour antigen-specific CARs for targeting cancer cells.

Question 26

List the currently approved CAR- T cell therapy

Answer 26

Yescarta and Kymriah.

Question 27

Facts about Allogeneic CAR T cell therapy

Answer 27

Allogeneic CAR-T cell therapy - engineering T cells isolated from healthy donors to target tumour-associated antigens in patients.

Question 28

Facts about BICE?

Answer 28

Bispecific Innate Cell Engager – AFM24
CD16A (FcγRIIIa) on natural killer (NK) cells and macrophages with a much higher affinity than monoclonal antibodies
NK cell‐mediated antibody-dependent cell-mediated cytotoxicity (ADCC)
Macrophage-mediated antibody-dependent cellular phagocytosis (ADCP)

Question 29

Facts About Autologous CAR-T-cell therapy

Answer 29

Autologous CAR-T-cell therapy -T cells derived from a patient are engineered as ‘living drugs’ to recognize and attack the patient’s own cancer cells. This patient-specific treatment involves the collection, preservation, shipment, genetic engineering and readministration of T cells from and into the same patient.