W10: Cancer Treatment

Antiestrogen - (tamoxifen)

D: Estrogen dependent anti-cancer drug

D: breast cancers

MOA: selective estrogen receptor modulator (SERM)- acts as a major competitive estrogen receptor antagonist.

MRM: loss of hormonal sensitivity (d/t increased or altered target receptor)

AE: long term use (5+ years) can result in endometrial cell proliferation and cancer.

Androgens - (testosterone, proprionate, fluoxymesterone)

D: Estrogen dependent anti-cancer drug

D: breast cancers

MOA: decrease estrogen by increasing testosterone via feedback loops in anterior pituitary

MRM: loss of hormonal sensitivity (d/t increased or altered target receptor)

AE: ?

Aromatase inhibitors - (Anastrozole, letrozole, exemestane, formestane)

D: Estrogen dependent anti-cancer drug

D: breast cancers

MOA: block action of CYP19 enzyme (converts testosterone into eostrogen), causing increased levels of testosterone and lower levels of estrogen, starving tumour.

MRM: loss of hormonal sensitivity (d/t increased or altered target receptor)

AE: ?

Estrogens - (Diethylstilbestrol (DES), Ethinylestriadiol)

D: Testosterone dependent anti-cancer drug

D: Prostate cancer

MOA: deprive tumour by increasing estrogen levels

MRM: loss of hormonal sensitivity (d/t increased or altered target receptor)

AE: ?

G: not phase specific

Antiadrogen - (Flutamide + Bicalutamide)

D: Testosterone dependent anti-cancer drug

D: Prostate cancer

MOA: block testicular and adrenal androgen production (inhibit receptor translocation to nucleus---stop message being sent to nucleus), decreasing testosterone.

MRM: loss of hormonal sensitivity (d/t increased or altered target receptor)

AE:

G: not phase specific

Antiadrogen - (Finasteride)

D: Testosterone dependent anti-cancer drug

D: Prostate cancer

MOA: Blocks 5a-reductase (converts testosterone into Dihydroteestosterone---most potent form), decreasing testosterone levels.

MRM: loss of hormonal sensitivity (d/t increased or altered target receptor)

AE:

G: not phase specific

Gonadotropin-Releasing Hormone Analog- (Leuprolide)

D: Testosterone dependent anti-cancer drug

D: Prostate cancer

MOA: decreases Estrogen (in women), and testosterone (in men)

MRM: ?

AE: ?

G: often given alongside Flutamide for prostate cancer.

CAN ALSO BE USED TO TREAT ESTROGEN DEPENDENT CANCERS-BREAST CANCER.

Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR TKI)--- Gefitinib Erlotinib

D: Specific tyrosine kinase inhibitor (TKI)

D: lung and pancreatic cancer

MOA: an over expression of EGFR linked to malignancy, these drugs act to inhibit EGFR expression

MRM: ?

AE: Skin, GIT toxicity, fluid retention

G: ?

Platelet Derived Growth Factor Receptor Tyrosine Kinase Inhibitor (PDGFR TKI)---Imatinib, Dosatinib, Nilotinib

D: Specific tyrosine kinase inhibitor (TKI)

D: chronic myeloid leukaemia cells (CML)

MOA: inhibits BCR-ABL enzyme which is vital for tumour survival

MRM: mutations in target gene (e.g. in BCR-ABL)

AE: Skin, GIT toxicity, fluid retention

G: Dosatinib, Nilotinib used to treat Imatinib resistant tumours

Angiostatin

D: Angiogenesis Inhibitor

D: Tumour growth inhibitor

MOA: endogenous inhibitor produced with plasminogen cleavage from matrix metalloproteinases from tumour cells

MRM: ?

AE: Renal (Proteinuria), Hypertension

G: ?

mAbs against VEGF--- Bevacizumab

D: Monoclonal antibody

D: Angiogenesis inhibitor

MOA: inhibits VEGF-A, decreasing the signal for blood vessel growth

MRM: extrinsic/intrinsic mechanisms evading VEGF dependence.

AE: Renal (Proteinuria), Hypertension

G: ?

VEGF receptor TKI--- vandetanib, sunitanib

D: Angiogenesis inhibitor

D: extrinsic/intrinsic mechanisms evading VEGF dependence.

MOA: inhibits VEGF, decreasing the signal for blood vessel growth

MRM: ?

AE: Renal (Proteinuria), Hypertension

G: ?

Thalidomide

D: Angiogenesis inhibitor

D: treats multiple myeloma when used with Dexamethasone.

MOA: used for antiangiogenic and immunomodulatory effect (inhibits TNF-a synthesis, and co-stimulates T-cell production), decreasing blood supply to tumours.

MRM:

AE: teratogenic

G: used alongside Dexamethasone to treat multiple myeloma. The second-generation drug is Lenalidomide.

Rituximab, Alemtozumab

D: mAB, DMARDs

D: Rheumatoid arthritis

MOA: Binds to CD 20 and marks

the B cells for attack by NK cells, reduces autoimmune attack

MRM: ?

AE: ?

G: ?