Targeted Therapies- Antineoplastic Flashcards
How do BCR-ABL inhibitors work?
Block TK, which blocks the downstream pathway that leads to cell proliferation
What does a Philadelphia Chromosome translocation lead to?
An expression of BCR and ABL, leading to unctrollable cell proliferation
What cancer is the Philadelphia chromosome closely related to?
Chronic myeloid leukemia
What are the BCR-ABL tyrosine kinase inhibitors?
Imatinib, Dasatinib, nilotinib
What it unique about dasatinibs ability compared to others in its class?
It can inhibit many TKs, but it can overcome Imatanib resistance
Which has higher binding affinity to Abl, Nilotinib or Imatinib?
Nilotinib
What are the Multi kinase RTKs Inhibitors?
Sunitinib, sorafenib, pazopanib
What do the Muli kinase RTKs inhibitors do?
Inhibit multiple receptor kinasases
What is the action of epidermal growth factor receptors?
Leads to cell proliferation, invasion, metastasis, and angiogenesis
This is overexpressed in several solid tumors
What is the murine percent of Mouse (omab)?
Chimeric (Ximab)?
Humanize (zumab)?
Human (umab)? Human
100%
33%
10%
100%
What is cetuximabs MOA?
chimeric mAb directed against extracellular EGFR domain
What can we know by looking at cetuximabs name?
xi, so highest murine content, so definitely hypersensitivity problems
What is critical to know about cetuximabs administration?
Should not be given with radiation of head/neck, can cause sudden death
What is panitumumabs MOA?
Fully humanized EGFR inhibitor
What is erlotinib and Lapatinibs MOA?
Inhibits INTRAcellular tyrosine kinase domain on EGFR
How is erlotinib and Lapatinib metabolized?
CYP3A4
What is an important note on Neratinib?
Its an irreversible HER2/EGFR inhibitor
What type of receptor is HER 1 and 2?
EGFR- Epidermanl Growth Factor Receptor
What are the HER 2 receptor inhibitors?
Trastuzumad and pertuzumab
What is Trastuzumabs MOA?
Humanized mAb, binds to domain IV on HER2 receptor, inhibiting signal transduction, also flags for cytotoxicity
What is the main ADE for trastuzumab and pertuzumab?
Cardiotoxicity
What is pertuzumabs MOA?
Humanized mAb, binds to domain II on HER2 receptor, inhibiting signal transduction, also flags for cytotoxicity
What are the two BRAF inhibitors?
Dabrafenib and Vemurafenib
What are BRAF inhibitors MOA?
Inhibit BRAF, which can be a constitutively active kinase pathway/component
What is the MEK inhibitor?
Trametinib, does what it sounds like
MEK is a downstream enzyme in the TK process
What is the VEGF inhibitor?
Bevacizumab and Ziv-alfibercept
What is VEGF?
Its one of the most important factors for angiogenic growth factors. Tumors secrete this to help growing.
What is bevacizumabs MOA?
Prevents VEGF from binding to the receptor
What is bevacizumabs ADE?
Hypertension
What is Ziv-afilbercepts MOA?
Creates a decoy receptor
What is Ziv-Afilbercepts ADEs?
Hypertension
What is bortezomibs MOA?
Inhibits proteasomes leading to excess protein in the cell and apoptosis
What are the mTOR inhibitors?
Everolimus, Temsirolimus
What do mutations in mTOR pathway result in?
Exaggerate signaling and enhanced cancer cell survival
What is everolimus active metabolite?
Sirolimus
What is the MOA of Thalidomide?
Anti MM Activity (Multiple Myeloma)
Inhibition of MM cell adhesion to bone marrow cells
Decreased angiogenesis
Enhanced T cell production and NK cells
What is Thalidomide NOT ok to use in?
Morning Sickness. Extremely teratogenic
What class is Rituximab?
Anti-CD20, basically destroys b cells (in cancer where B cells are rogue)
What is Rituximabs ADE?
Chimeric, “xi”, so reactions
What is Ipilimumabs MOA?
Inhibits cytotoxic T lymphocyte antigen 4, so it ensures T cell activity is regained
What is Pembrolizumads MOA?
Inhibits PD-1 (which is something that cancer cells use to help avoid getting destroyed by the body), so ensures programmed cell death can occur
