TREATMENT OF CANCER Flashcards
How does chemotherapy work?
it kills cells that are rapidly dividing and cancer cells divide the fastest
chemotherapy isnt targeted but outline how some specificty occurs?
cancer cells are unable to repair DNA damage whilst normal cells can
why do we use combination chemotherapy?
chemotherapy drugs affect cancer cells at different points in the cell cycle, using a combination of drugs increases the chance that all of the cancer cells will be eliminated.
what are some aims of chemotherapy?
curative
adjuvant given after a radiotherapy/surgery
neo-adjuvant - given before rasdiotherapy/surgery
palliatively
what are the classes of chemotherapy agents?
alkylating agents, plant alkaloids, antimetabolites, anthracyclines, topoisomerase inhibitors and corticosteroids.
what percentage of cancer patients have radiotherapy during the course of their disease?
50%
what strength radiation is radiotherapy?
Mega voltage radiation
what is compton scattering?
the scattering of a photon after an interaction with a charger particle, usually an electron
outline the mechanism of radiotherapy?
ionising radiation ionises water and oxygen which creates free radicals which cause DNA damage.
what are the 2 types of radiotherapy?
external beam radiotherapy
brachytherapy
why is radiotherapy given as fractions?
so that the healthy tissue that is damaged can recover in between doses
what is the proces of conventional external beam irradiation?
2-D beams use kilo voltage therapy x-ray units to generate high energy X-rays
what is stereotactic radiotherapy used for?
used for small, isolated tumors outside the brain and spinal cord, often in the liver or lung. It may be an option when you cannot have surgery due to age, health problems, or the location of the tumor.
what is 3D conformal radiation therapy?
a cancer treatment that shapes the radiation beams to match the shape of the tumor.
what is brachytherapy?
internal radiation therapy which is achieved by putting a sealed or unsealed source of radiation inside or next to the area requiring treatment
pros and cons or brachytherapy?
tumour can be treated with very high doses in a small time frame
but tumour must be accessible and well-demarcated
what is a Gray?
1 joule of energy absorbed per KG of matter
what is fractionated radiotherapy?
when radiotherapy is given over several days and each dose is called a fraction. Typical doses for a fraction are 2Gy (gray)
what are the differences between chemotherapy and radiotherapy?
chemo targets proliferating cells whilst radio targets the tumour
chemo uses drugs and radio uses high energy waves
chemo targets multiple parts of the body whilst radio targets a single area
what are the side effects of chemo?
alopecia stomatitis and mucotitis nausea and vomiting immunosuppression anaemia bleeding/bruising (pancytopenia)
what is chronic toxicity?
the development of adverse effects as the result of long term exposure to a toxicant or other stressor
what are the acute side effects of radiotherapy?
erythematous, itchy, dry skin oesophagitis dysphagia cough and shortness of breath nausea vomiting anaemia leucopenia leathery myelitis
what are the chronic side effects of radiotherapy?
infertility hair loss fibrosis telangiectasia late ulceration fistula structure necrosis growth retardation myelofiborisis permanent nerve damage
what is a risk of having chemo/radiotherapy at younger ages?
the chance of secondary cancers
what are some modes of resistance to anticancer drugs?
change in binding affinity to target enzymes formation of drug-inactivating enzymes production of reactive chemicals increased nucleic acid repair mechanisms reduced activation of pro-drugs
what is MDR1?
multidrug resistance mutation 1
what is MDR1?
multidrug resistance mutation 1
what is MDR1?
multidrug resistance mutation 1
how does MDR1 work?
The MDR1 gene codes for the production of a protein known as p-glycoprotein. This sits on the cell membrane of these cancer cells and pumps chemotherapy drugs out of the cell. = resists chemotherapy drugs
what is primary reisstance?
when a malignant tumour doesnt respond to immunotherapy
what is adaptive resistance?
when a cancer is recognized by the immune system but it protects itself by adapting to the immune attack.
what are some limitations of cytotoxic chemotherapy?
- lacks specifity
- toxic and side effects
- lack of effectiveness
- lack of individualism
whats the function of epidermal growth factor receptor (EGFR)?
signalling molecules bind to it and cause downstream signalling which results in signal transduction cascade leading to DNA synthesis and cell proliferation
what can overexpression of EGFR cause?
uncontrolled cell division = cancers
how has the recognition of the EGFR receptor been used in pharmacology?
EGFR inhibitors
monoclonal antibodies that block the extracellular ligand binding domain
inhibitors of EGFR tyrosine kinase
what is PD-1 and PD-L1?
programmed cell death protein 1 and its ligand
what happens when PD-1 and PD-L1 bind?
it helps keep T cells from killing other cells, including cancer cells.
so we use these as drug targets
what is an example of a PD-1 inhibitor?
permbrolizumab
whats an example of a PD-L1 inhibitor?
atexolizumab
what is CTLA-4?
cytotoxic T-lymphocyte associated protein 4 (inhibits immune cell activity)
what is the angiogenic switch?
when a tumour starts to stimulate the growth of new blood vessels
whats the principle stimulus for the angiogenic switch?
oxygen deprivation
what are some examples of pro-angiogenic factors?
angiogen
vascular endothelial growth factor
fibroblast growth factor
transforming growth factor
how can we, pharmacologically, inhibit angiogensis?
with vascular endothelial growth factor inhibitors (VEGF)
what are some common side effects of EGFR inhibitors?
papulopastular rash across face and torso diarrhoea nausea vomiting fatigue dehydration
what are some common side effects of EGFR inhibitors?
papulopastular rash across face and torso diarrhoea nausea vomiting fatigue dehydration
what are some side effects of immune checkpoint inhibitors e.g. PD-1 inhibitors?
◦ fatigue ◦ nausea ◦ loss of appetite ◦ skin rash ◦ itching
what are some side effects of immune checkpoint inhibitors e.g. PD-1 inhibitors?
fatigue ◦ nausea ◦ loss of appetite ◦ skin rash ◦ itching
what are some side effects of immune checkpoint inhibitors e.g. PD-1 inhibitors?
fatigue nausea loss of appetite skin rash itching
what are some common side effects of angiogenic inhibitors?
bleeding increased bp rash / itchy skin diarrhoea fatigue low blood counts
