Pathway Targeted Therapies Flashcards
EGFR Tyrosine Kinase Inhibitors (TKIs)
Erlotinib, Gefitinib, Afatinib, Osimertinib
Antibody inhibitors of EGFRs
Cetuximab, Panitumumab, Necitumumab
Antibody inhibitors of HER2/Neu
Trastuzumab and Pertuzumab
HER2/Neu TKIs
Lapatinib and Neratinib
Inhibitors of mutated RAF kinase
Vemurafenib and Dabrafenib
Inhibitors of MEK
Trametinib and Cobimetinib
Cyclin Dependent Kinase (CDK 4/6 inhibitors)
Palbociclib, Abemaciclib, and Ribociclib
Inhibitors of Histone Deacetylase?
Panobinostat and Romidepsin
Anti-CTLA4
Ipilimumab
Anti-PD1
Nivolumab and Pembrolizumab
AntiPDL1
Atezolimumab
Inhibitors of BCR-ABL Kinase
EGFR TKIs (Imatinib, Dasatinib, Nilotinib)
Drugs targeting Angiogenesis
Bevacizumab, Afilbercept, Ramucirumab, TKIs (pazopanib, sorafenib, sunitinib)
What is targeted cancer therapies?
drugs that block the growth and spread of cancer by interfering with specific molecules that drive malignant progression of human cancers
Targeted cancer therapy vs. standard chemo
acts on specific molecular targets
deliberately chosen to interact with target
cytostatic (block tumor cell proliferation)
Antibody drugs–combine biologic and cytotoxic mechanisms
Targeted Cancer Therapies
Growth factors and receptors in cancer
Intracellular Kinases
Tumor host interactions aberrant tumor angiogenesis
restoring immune recognition
targets that control cancer cell behavior
EGFR binding MOA
Phosphorylation of downstream adapter proteins (MAPK, PI3K/Akt, and STAT)—>stimulates signaling pathways–>cell growth and proliferation
Epithelial cancers?
overexpression of EGFR and mutational activation of EGFR—>dependence of EGFR signaling
Drugs that target the EGFR Pathway?
TKIs or monoclonal antibodies
Erlotinib MOA?
reversible inhibitor of EGFR TK–>competively inhibits ATP binding as the active site of the kinase
Erlotinib and PPIs?
PPIs decrease Elotinib bioavailabilty by 50%
Erlotinib and Warfarin?
Poor extrinsic coagulation (elevated INR)
Erlotinib Usage?
Advanced or metastatic NSCLC after failure of Platnium based treatment
Approved for patients with EGFR mutations ONLY
Gefitinib absorption?
reduced by drugs that cause elevations in gastric pH
Afatinib MOA
Irreversible inhibitor of EGFR and HER2 receptor kinases
Afatinib is a substrate of
Pgp
what is first line treatment for metastatic NSCLC with EGFR mutations?
Afatinib
EGFR gatekeeper residue T790M
prevents binding of TKIs
It is an acquired second EGFR mutation
Osimertinib (3rd gen) is for?
T790M mutant EGFR treatment-use if resistant to TKI
Osimertinib MOA?
irreversible inhibitor of T790M-mutant EGFR
C797S is?
A third mutation; resistance to Osimertinib
Cetuximab MOA?
Antibody that binds to extracellular domain III EGFR–>prevents ligand dependent signaling and receptor dimerization –blocks cell growth/survival
Cetuximab use?
Metastatic colon cancers (KRAS wild type)
Head and neck squamous cell carcinoma
Cetuximab AE?
infusion reactions
fetal harm