3 Chemotherapy Biologics Flashcards
Describe the principle of targeted anticancer therapy
They exploit biological weaknesses in tumors
- Faulty genes
- Faulty signalling systems
- Tumour growth
- Angiogenesis
Describe hormonally targeted drugs
May antagonize hormones responsible for promoting tumor growth
e.g. oestrogens in breast cancer
Describe chemotherapy biologics
It is the molecular testing of cancer cells to determine receptor expression
Describe the principle of hormone-based therapy
Oestrogen promotes tumour spread (allows metastasis from local site to a distant site)
Describe the mechanism of action of tamoxifen (hormone-based drug)
Tamoxifen blocks estrogen as a selective estrogen-receptor modulator (SERM)
- It binds to receptors + reduces/modulates/modifies their activation by estrogen
- It reduces the growth of estrogen-driven breast cancer, hence preventing breast cancer (used in estrogen receptor +ve breast cancer)
- It is a prodrug (needs to be activated - some people may not have the isoenzymes required to activate it)
As a receptor modular
- Tamoxifen prevents bone loss via oestrogenic effects
Describe the mechanism of action of aromatase inhibitors
In post-menopausal women, there is the peripheral conversion of androgens to estrogens by the enzyme Aromatase > so increasing the likelihood of tumor spread (i.e. more estrogen)
- e.g. Anastrozole prevents the peripheral conversion of androgens to estrogens in post-menopausal women
- It is used in the treatment of breast cancer in post-menopausal women
Describe the role of the HER2 receptor in the contribution of cancer proliferation (hence how it can be targeted by therapeutic agents)
- Human epidermal growth factor receptor 2 (HER2) is naturally present in low levels
- But it is overexpressed in some cancers; e.g. 25% of breast cancers are HER2+
So, the overexpression of HER2 receptors activates tyrosine kinase (autophosphorylation)
- this then triggers multiple signaling cascades in the cell, leading to dysregulation of the cell cycle,
- and in the nucleus, there is increased transcription,
- leading to the production of chemicals that all contribute to increased cancer cell proliferation (VEGF, COX2, Cyclines)
Describe the mechanism of action of trastuzumab
It is a monoclonal antibody (mAb)
- It targets HER2 receptors
- Used for early breast cancer and metastatic breast cancer with HER2+ tumors
Describe the role of epidermal growth factor (EGF) receptor in the proliferation of cancer (and hence how can it be targeted by therapeutic agents)
- EGF receptor works in a similar way to HER2, by activating TK molecules,
- which then subsequently activate multiple signalling cascades,
- leading to the production of chemicals that initiate invasion, angiogenesis, inhibition of apoptosis, which all induce cell proliferation
Describe the mechanism of action of erlotinib
- Works in the same ‘small molecule’ approach, by inhibiting the EGF receptor, thus reducing cancer cell proliferation
- Used for certain lung and pancreatic cancers
Describe the mechanism of action of imatinib (TK inh..)
Imatinib is a tyrosine kinase (TK) inhibitor
- Tyrosine kinase leads to uncontrolled cell proliferation, and imatinib inhibits this
- It is a selective inhibitor of TK and is very effective for chronic myeloid leukaemia (CML)
Describe why proteasomes are important to cancer cells
Proteasomes are molecules which degrade unneeded/damaged proteins
- Cancer cells are more dependent on the proteasomes for clearance of abnormal or mutant proteins than the normal cell
Describe the mechanism of action of Bortezomib
Bortezomib is a proteasome inhibitor and is used in multiple myeloma
- Inhibitors of proteasomes should prevent malignant cells from proliferating
Describe the role of Vascular Endothelial Growth Factor (VEGF) receptor in cancer proliferation (hence, how to target this)
VEGF is:
- Secreted to promote angiogenesis (blood vessel growth to support metastasis)
Describe the mechanism of action of sunitinib
Sunitinib is an angiogenesis inhibitor
- It inhibits VEGF-associated tyrosine kinase (TK)
- used in advanced renal carcinoma
