5.2 Cancer therapies: cytotoxics to targeted therapies Flashcards Preview

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Flashcards in 5.2 Cancer therapies: cytotoxics to targeted therapies Deck (23):

What are the phases of drug assessment?

In vitro: shows activity in cell lines
Preclinical: animal models
Phase I: clinical assessment - dose finding
Phase II: Safety and efficacy assessment in various tumours
Phase III: comparing against best available treatment
Phase IV: post marketing safety surveillance


How does chemotherapy work?

Effect cellular division which promotes apoptosis. There is no selection for tumour cells but normal cells are thought to be able to recover better.
Works best against dividing cells


Which cancer is chemo used as curative?

Paediatric tumours, germ cell malignancies, leukaemia, lymphomas


What are monoclonal antibodies?

Proteins synthesised to bind onto specific ligands, tumour cel proteins or receptors on the cell surface necessary for tumour growth and neutralize their action


What are small molecule inhibitors?

Block the activity of a signalling pathway inside the cells to prevent tumour growth


What is the target for rutiximab and what is it used for?

CD 20 in lymphoma


What is transtuzumab, what is its trade name and what is it used for?

Her2 receptor - Herceptin in breast cancer and gastric cancer


What is imatinib, what does it target and what is it used for?

Glivec, c-KIT and bcr-abl used in GIST and CML
(small molecule transduction inhibitor)


What is the role of Her2?

The Her2 receptors play a key role in cell growth and survival. Over expression or mutation leads to increased proliferation of the cancer cells.

Promotes invasion, survival and angiogenesis of cancer cells


How to you determine Her status?

Immunohistochemistry to look for the receptors


What are the strategies for inhibiting Her2?

Transtuzumab (Herceptin): monoclonal antibody to block ligand binding or receptor dimerization

Lapatinib (Tykerb): small molecule kinase inhibitor


What is the main toxicity of transtuzumab?

Reversible cardiotoxicity


What is transtuzumab emtansine and when is it used?

monoclonal antibody trastuzumab (Herceptin) linked to the cytotoxic agent DM1. This enters the cell and causes damage this way. Used in transtuzumab resistant Her2+ breast cancer


What is Lapatinib and when is it used?

Small molecule dual kinase inhibitor (EGFR or Her2) and is used in transtuzumab resistant advanced cancer in combination with Xeloda


What is the theory behind targeting VEGFR?

Causes regression of tumour microvasculature and normalisation of surviving mature vasculature to improve access of chemo drugs and inhibits new vessel growth


What is EGFR

EGFR is a regulator of cell cycle progression, repair and survival and is involved in tumour metastases


What is Bevacizumab and what is it used for?

Monoclonal antibody to VEGF
Works in metastatic colorectal, NSCLC, Breat and renal cell cancer


What is Cetuximab and what is it used for?

IgG monoclonal antibody against EGFR the blocks EGFR and inhibits proliferation, angiogenesis and metastases and stimulates apoptosis

Used for EGFR positive colorectal and head and neck


What is the marker in colorectal patients to indicate cetuximab (anti EGFR) usage?

K-RAS and NRAS wild type will respond to anti EGFR therapy


What is the main side effect of cetuximab?

Acneiform rash - severity of which indicate positive response


What are the tyrosine kinase inhibitors drugs of EGFR and what are the side effects?


Side effects: rash and diarrhoea


What is Ipilimumab and what is it used for?

Anti CTLA-4 monoclonal antibody which blocks T cell activation - used for melanoma


What is Dabrafenib and what is it used for?

Inhibitor of BRAF which blocks the MAPK pathway used for melanoma