Targeted cancer treatments Flashcards
Endogenous VEGF signalling roles
VEGFA acts at VEGFR2 to mediate angiogenesis and development of several organ systems.
VEGFA inhibitor
Bevacizumab is a monoclonal antibody for the ligand VEGFA.
It is used to treat metastatic colorectal cancer, non-small-cell lung cancer, renal cell carcinoma, glioblastoma, breast and ovarian cancers.
It is used in conjunction with 5-flurouracil.
monoclonal VEGFR2 inhibitor
Ramucirumab is a monoclonal antibody for the VEGFR2 receptor.
Binds to the ligand binding site and antagonises the receptor.
Approved for non-small-cell lung cancer, metastatic colorectal cancer and gastric cancers.
Often used in conjunction with 5-fluorouracil.
May see increased VEGF levels from up regulation - homeostasis.
Small-molecule VEGFR2 inhibitors
e.g., sorafenib and axitinib.
Both are RTK inhibitors.
Sorafenib targets several RTKs, including c-Raf, B-Raf, PDGFRs and VEGFRs. Treats renal cell carcinoma, hepatocellulr carcinoma and thyroid cancers.
Axitinib targets VEGFR1/2/3, c-KIT, and PDGFRs. it is approved for renal cell carcinoma. Generally second-line treatment if multi-target RTKI ineffective
RTKIs are antiproliferative and antiangiogenic
Adverse affects of VEGF antagonism
Hypertension due to VEGFR2 mediated generation of NO and PGI2.
Arterial thrombotic events due to VEGF role in platelet homeostasis.
Haemorrhage risk in lung and GIST tumours.
Renal adverse events due to VEGFR2 mediating glomerular normal function/repair.
Wound complications due to VEGF’s involvement in coagulation cascade and platelet homeostasis.
HER2 monoclonal antibody mechanism
Trastuzumab inhibits HER2 by binding to EC domain to treat HER2-positive breast cancers.
HER2 mediates cell cycle control, growth and angiogenesis.
Often used in combo with chemo
Commonly causes cardiotoxicity. Can cause pain, GI issues, pulmonary symptoms.
ER inhibitors mechanism and side effects
Tamoxifen is a selective ER antagonist.
The ER is over expressed in 70% of breast cancers.
Given for 5 years following surgical resection
Can induce mitochondrial damage
Side effects include hot flushes, nausea, sweating, fatigue, weight gain, waginal bleeding.
Longterm use can increase risk of endometrial cancer
CAR-T therapy mechanism
a form of immunotherapy, which uses patients immune cell to treat the condition.
T cells derived from patients blood are engineered to express artificial receptors for the tumours antigen. Highly successful treatment.
Highly complex and risk.
HPV vaccine
Can be quadrivalent (e.g., gardisil) or bivalent (e.g., cervarix)
Vaccine for HPV, a major cause of cervical cancer.
Cancer given as a preventative measure
Generally have mild side effects that are also quite rare.
