Hormonal therapy 2 Flashcards
7How does CDk4/6 inhibitors work?
Block phosphorylation of Rb, leads to G1 arrest.
This decreases the appearance of resistance to hormonal chemotherapy
List examples of CDK4/6 inhibitors
Ribociclib
Palbociclib
State the treatment options for prostate cancer
Watchful waiting
Active surveillance
Surgery
Hormonal therapy
Chemotherapy
Radiotherapy
List the first two strategies used in Prostate cancer treatment
Androgen Deprivation Therapy (ADT)
Orchidectomy
GnRH agonist
Combined Androgen Blockade
GnRH agonist
Antiandrogen
State additive hormonal manipulation in Prostate cancer
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
Facts about GNRH antagonists used in Prostate cancer
Competitive inhibition of GnRH binding such as
Cetrorelix, dagarelix
Facts about antiandrogens used in Prostate cancer
inhibit the DHT-receptor complex formation eg flutamide, cyproterone, bicalutamide
Bone pain and tumour size are reduced
Gynaemastia an issue
Enzalutamide is an antiandrogen used in Prostate cancer in later stage and its more effective than Bicalutamide. True/false?
True
State the role of Abiraterone
blocks endogenous androgen production by inhibiting CYP17A1 (P450)
State how finasteride work in Prostate cancer
Block the 5-alpha reductase enzyme
Converts testosterone to DHT
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?
Anastrazole
CDK4/6 form a complex with X which, when activated by oestrogen receptor, leads to progression through the cell cycle.
Cyclin D
Ribociclib binds to the Cyclin D:CDK4/6 complex, blocking the phosphorylation and inhibition of X which leads to cell cycle arrest.
pRB
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.
Bicalutamide
RITUXIMAB is a biological agent that binds to….
CD20 on Bcells and makes them visible
RITUXIMAB is used to treat….
Lymphomas and Leukaemia
State the three mechanisms of action of RITUXIMAB
- Complement mediated toxicity
2.Antibody dependent cell mediated toxicity - Activation of caspases and apoptosis
What is CTLA-4 ?
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell activation
State the mechanism of action of Ipilimumab
Ipilimumab is a monoclonal antibody that binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86
Ipilimumab is used to treat…
Ipilimumab approved for melanoma and renal tumours but significant side effects such as skin rash
What drug has a better treatment profile than Ipilimumab?
PD-1/PD-L1 inhibitors
List examples of PD-1/PD-L1 inhibitors?
Pembrolizumab and Nivolumab
State how immunotherapy such as pembrolizumab works
Either bind to PD-1 or PD-L1
Tumour cell now no longer ‘hidden’ from the immune response
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.
Pembrolizumab/Nivolumab
What is CAR-T cell therapy?
CAR-T cell therapy involves using engineered T cells expressing tumour antigen-specific CARs for targeting cancer cells.
List the currently approved CAR- T cell therapy
Yescarta and Kymriah.
Facts about Allogeneic CAR T cell therapy
Allogeneic CAR-T cell therapy - engineering T cells isolated from healthy donors to target tumour-associated antigens in patients.
Facts about BICE?
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)
Facts About Autologous CAR-T-cell therapy
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.
