LM 12.1: Systemic Therapies for Cancer Flashcards
what’s the rationale behind targeted cancer therapy?
understanding the molecular dependencies and vulnerabilities (weaknesses) and use that to exploit cancer
what three things dictate if a cancer cell proliferates or dies?
- network of regulatory factors like TF and transcription repressors
- tumor microenvironemtn like growth factors and cytokines, M2 macrophages and high collagen content
- stress signals like DNA damage
oncogenes and tumor suppressor genes oppose each other
the net effect of these interactions along with the help from the tumor microenvironment (TME) and DNA damage dictate cancer growth.
what is targeted therapy?
refers to a new generation of anti-cancer agents designed to interfered with a specific molecular target that plays a critical or vital role in tumor progression and
metastasis
targeted therapy aims to fight the tumor only based on its unique vulnerabilities
what is conventional therapy?
more empirical and is based on non-specific cytotoxic chemotherapeutics
conventional therapy targets the entire body of the patient
what are targeted anticancer agents?
can be small molecule inhibitors or humanized neutralizing antibodies
typically the names of small molecule inhibitors (SMI) end in “ib” or “in” or “stat”
therapeutic monoclonal antibodies en in “mab”
what is erlotinib?
small molecule inhibitors (SMI)
an inhibitor that targets epidermal growth factor receptor (EGFR)
what is midostaurin?
small molecule inhibitors (SMI)
targets FLT3 receptor
what is Transtuzumab?
therapeutic monoclonal antibodies
monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2)
how do you differentiate between human and mouse genes?
human genes are capitalized and mouse genes are lower case
SRC vs src
what are monoclonal antibodies?
they target antibodies
mab = monoclonal antibody
ximab = chimeric human-mouse antibody
zumab = humanized mouse antibody
mumab = fully human antibodies
what is personalized medicine?
identifies the somatic mutations or application of pathway networks in the cancer lesions of patients and targeting them accordingly
what is precision medicine?
this phrase was favored over “personalized medicine” because the tumors are precisely targeted for driver mutations and key amplified pathways
do you usually treat cancer with one drug?
targeted mono therapy (one drug against a given target) often doesn’t work because there’s drug resistance and cancer relapse
so you usually do a combination of drugs with or without radiotherapy
what are the different combinations of treatment you can do to treat cancer?
- surgery followed by mono- or radiotherapy
- targeted therapy + conventional chemo
- targeted therapy against two molecules simultaneously
- targeted therapy combined with immunotherapy
what are A1 targeting agents?
they target DNA replication, transcription and DNA damage repair
A1 drugs target:
1. topoisomerase
- epigenetic factors (HDACs)
- poly ADP ribose polymerase
what drugs target topoisomerase?
epirubicin
what drugs target HDACs?
romidepsin (istodax)
panobinostat (farydak)
belinostat (beleodaq)
which drugs target poly ADP ribose polymerases?
rucaparib (rubraca)
olaparib (lynparza)
niraparib (zejula)
what are A2 systemic targeting agents?
they target the cell cycle
the issue with these is that when cell cycle inhibitors are employed, all actively dividing cells in the body are targeted
so patients of reproductive age may have side effects and immune surveillance of tumors are further compromised
positive effects may be on pro-tumor immune cells like M2 macrophages and regulatory T cells
A2 drugs target CDK4/6 and HDM2
which drugs target CDK4/6?
palbociclib (ibrance)
ribociclib (kisqali)
what do drugs that target HDM2 do?
HDM2 is a homolog of MDM2 and regulates p53 by degrading it
so inhibition of HDM2 would up regulate p53 and give cells control over their cell cycle
however, HDM2 inhibitors will only work if the p53 is a wild type and will NOT work if p53 is mutated or deleted
what are A3 systemic targeting agents?
they target cell signaling
they target:
1. receptor tyrosin kinases
- G-protein coupled receptors (GPCRs)
- hormone receptors
- other kinases
what are the different types of receptor tyrosine kinases that A3 targeting agents target?
- EGF receptor
- human EGF receptor 2 (HER2)
- vascular endothelial growth factor receptor 2 (VEGFR2)
- Janus Kinase 1/2 (JAK1/2)
- insulin-like growth factor 1 receptor (IGF1-R)
which drugs target EGF receptors?
- monoclonal antibodies
- cetuximab
- panitimumab - SMI
- tyrosine kinase inhibitors (TKIs)
- erlotinib
- gefitinib
