Exam (elaborations)
PHCY320 ON7 Targeted Therapies Exam Latest Update
- Course
- Institution
PHCY320 ON7 Targeted Therapies Exam Latest Update ...
[Show more]
Content preview
PHCY320 ON7 Targeted TherapiesExam Latest Update
Targeted therapies differ from standard cancer therapies in that - Answer Act on
specific molecular target(proteins that control how cancer cells grow, divide & spread),
generally cytostatic and are products of rational drug design.
Cytostatic - Answer Inhibits cell growth and proliferation.
Targeted therapies are the cornerstone of precision medicines where using - Answer
Information about genes & proteins can help diagnose and treat. This helps target
survival and growth pathways and improve outcomes/minimise adverse effects.
Normal tumour-suppressor gene acts as - Answer Brake for cell growth.
Normal proto-oncogene acts as - Answer Accelerator for cell growth.
Abnormal cell cycle (cancer cells) caused by - Answer Mutated tumour-suppressor gene
-> loss of function &/or mutated proto-oncogene -> gain of function.
Oncogenic pathways - Answer Spontaneous undesired mutations -> activate
proto-oncogenes -> inactivate tumour-suppressing & DNA repair genes.
Can also overexpression of growth factors & enzymes -> gain of function -> increased
cell proliferation.
Tumour associated antigens (TAIs) are - Answer Molecules involved in oncogenic
pathways (optimal blocking targets to prevent cancer cell proliferation).
Receptor tyrosine kinase (RTK) mediates - Answer Cell-cell communication, regulates
eg. growth, motility, differentiation. All 58 known RTKs in humans have inherent tyrosine
kinase activity & can auto-phosphorylate -> activation & promotion of cell growth.
Dysregulation of RTK signalling leads to - Answer Many human diseases especially
cancer.
Three examples of RTKs - Answer VEGF Rs (vascular endothelium-derived growth
factor), HE Rs (human epidermal growth factor), PDGF Rs (platelet-derived growth
factor).
Under normal physiological conditions, RTK activity is tightly balanced. - Answer
Growth factor ligand binds -> dimerisation -> auto-phosphorylation -> R activated.
When oncogenes are activated -> RTK production -> - Answer Auto-phosphorylation ->
always on -> stimulates proliferation & blocks apoptosis.
, -tinib drug means - Answer A small molecule inhibitor of the RTK.
Tyrosin kinase inhibitors (eg. gefitinib, erlotinib, sorafenib, sunitinib, and dasatinib) MoA
- Answer Competitive inhibition of ATP binding at RTK catalytic site BUT each have
different spectrum of targeted kinases.
Sunitinib inhibits signals from several Rs including - Answer VEGF and PDGFR families.
Rare SE: osteonecrosis of the jaw esp w radiation or bisphosphonates.
Fusion genes are potential therapeutic targets based on rationale of - Answer
Chromosomal abnormalities in cancer cells but not normal cells. Fusion genes -> fusion
proteins -> drive cancer development.
Fusion gene is when - Answer The gene incorporates parts of two different genes.
Chronic myeloid leukaemia is associated with - Answer Philadelphia chromosomes ->
BCR-ABL mutation -> BCR-ABL fusion protein -> constitutively active tyrosine kinase
activity.
Imatinib (Gleevec) is the first NIB approved by FDA MoA - Answer Small molecule
intracellular inhibitor selective for BCR-ABL TK fusion protein, used in chronic myeloid
leukaemia. It competes with ATP for binding site -> inhibits phosphorylation -> turn off
constitutive activation of TK -> prevents cell proliferation.
RTK inhibitor (-nibs) Side effects - Answer Usually well tolerated, myelosuppression,
rash, GI upset, fatigue, arthralgia, myalgia; (rare) cumulative cardiotoxicity,
osteonecrosis(sunitinib)
Pt taking nibs Monitoring - Answer Cardiovascular functions.
RTK inhibitor (-nibs) Interactions - Answer CYP3A4 substrates eg. rifampicin(inducer)
increase clearance of nibs, fluconazole(inhibitor) decreases clearance by 30%
(clinically sig).
Rifampicin induces/inhibits CYP3A4? - Answer Induces.
Fluconazole induces/inhibits CYP3A4? - Answer Inhibits.
-ciclib (newer ibs) means - Answer Cyclin-dependent kinase inhibitor.
-mab means - Answer Monoclonal antibodies which binds to specific antigen epitopes
(historically used to assess molecular phenotype).
Standard nomenclature of MABs - Answer Preceding the -mab is animal source:
o(murine), i(primate), xi(chimeric), zu(humanised), u(human).
MABs MoA - Answer Targets angiogenesis especially VEGF-A and VEGFR2 (keys in
angiogenesis).
Angiogenesis - Answer New blood vessel formation(normally tightly controlled). It is
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller Zayla. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $11.99. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
81311 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy study notes for 14 years now