introduction to cancer therapy 1 Flashcards
what are the traditional treatments for cancer
surgery, radiation, chemotherapy
what are examples of precision medicine
targeted therapy and immunotherapy
what is cancer chemotherapy
therapy that involves administration of chemical agents to destroy cancer cells
what was the first cancer drug developed from
mustard gas
mustard gas is a type of what agent
alkylating agent
how did they discover the first cancer drug
from mustard gas accident during WW2, the men exposed had a lower white count
why can cancer change their genomes rapidly
due to a lack of DNA repair machinery and they are very plastic
cancer don’t have DNA repair machinery this allows them to quickly develop
resistance
neoadjuvant chemotherapy is what?
administrated prior to surgery to facilitate resection and prevent metastasis
adjuvant chemotherapy is what
after surgery, reduce risk of distant relapse and increase disease-free survival
palliative chemotherapy is
improve patients quality of life by controlling symptoms in a patient where a cure in unlikely
salvage chemotherapy is
potentially curative, high-dose regimen given to a patient who has failed/reccurred in prior regimen
what are the four types of chemotherapy
- neoadjuvant
- adjuvant
- palliative
- salvage
what are cytotoxic drugs
these kill dividing cells, as a consequence these kill healthy cells which makes the patient immunosuppressed
what are the 5 functions of chemo drugs
- antimetabolites
- topoisomerase enzymes
- structural damage
- disturbed function of the mitotic spindle
- hormonal agents
what are antimetabolites
limit the synthesis of nucleic acid precursors, and structural analogues. S phase specific
what is the function of topoisomerase enzymes
participate in the winding and unwinding of DNA are inhibited
what are structural damage drugs
structural damage to mature DNA
what are example of a drug that affects the mitotic spindle
vinca alkaloids
what is the function of hormonal agents drugs
block proliferation of hormone-response cells
what is the mechanism of alkylating agents
target DNA, produce alkylation through formation of intermediate. the drug enters through a chloride transporter and inside the cell they are hydrolysed. the hydrolysis results in an active species which binds to DNA in a way that can’t be repaired.
which type of chemotherapy drug is not cell cycle phase specific
alkylating agents
what are intermediates
block damaged DNA
what is the mechanism of antimetabolites
interfere with DNA synthesis
which type of drug is S-phase specific
antimetabolites
what are mitotic spindle agents mechanism of action
bind to microtubular proteins inhibiting microtubule assembly thereby interrupting the mitosis phase of cell division
what are topoisomerase inhibitors mechanism of action
DNA topoisomerase I and II are essential for transcription and replication and mitosis. Regulates structure and winding of DNA
what are the 5 principles of combination chemotherapy?
- use drugs as a single agent
- use drugs with different mechanisms of resistance
- use drugs with different side effects
- be aware of drug to drug interactions
- use drugs with different mechanisms of action
what types of cancer can be found in category 1 responsiveness to efficacy
germ cell, lymphomas, leukemias
what types of cancer can be found in category 2 responsiveness to efficacy
breast, colorectal, ovarian
what types of cancer can be found in category 3 responsiveness to efficacy
lung, bladder, prostate, stomach, cervical
what types of cancer can be found in category 4 responsiveness to efficacy
head and neck
what types of cancer can be found in category 5 responsiveness to efficacy
liver, melanoma, brain, thyroid and renal
what types of cancer have a high response and a high cure rate
childhood cancer, testicular, choriocarcinoma, Hodgkin Disease
what types of cancer have a high response and low cure rate
breast, ovarian, small cell lung cancer, sarcoma, myeloma
what types of cancer have a low response and a low cure rate
colon, stomach, prostate, pancreatic, glioblastic, non-small cell lung cancer
what are the survival parameters
- disease-free survival
2. overall survival
what is disease- free survival
from the time of treatment to first recurrence
what is overall survival
from time of diagnosis to death
how can chemo be delivered
intravenous or orally
why can chemotherapy make someone immunosuppressed?
because chemo targets the bone marrow
what factors can boost the immune system
G-CSF
what can prevent a cancer patient from becoming immunosuppressed
blood fusion
what type of drug induces sickness symptoms
platinum anthracylines alkylatings
what is cardiotoxicity and who is most affected
when the heart muscle is injured, children
what is pulmonary toxicity and how can you treat it
damaged to the lungs, treat with corticosteroids
what is nephrotoxicity, how can you treat it
rapid deterioration of the kidney, treat by making sure the patient receives adequate hydration
what is gondal damage, what should you do?
damage to the gonads, preserve the stem cells
what should you do with secondary malignancies
avoid the responsible drug
what is oral mucositis
a common complication of cancer where the mucosal lining of the mouth begins to atrophy and breakdown forming ulcers and sores.
symptoms of mucositis
burning, oral pain, difficulty eating, drinking and talking and difficulty with mouth care
how do you treat mucositis
protect lips with moisturiser, avoid acidic foods and regular mouthwash
how can you become resistant to chemotherapy
- tumours can acquire resistance
- cytotoxic drugs revoke drug resistance
- effects drugs of similar structure
resistance in chemotherapy is often due too
mutation or altered gene expression of genes which:
- transport drug in our out of the cell
- metabolism and intracellular concentration of the drug
- structure of the target protein which binds causing toxicity
- protection from apoptosis
What are the characteristics of cancer stem cells
quiescent, increased expression of anti-apoptotic proteins and increased activity of pro-survival pathways
what gene is a multi-drug resistance gene
MDR1
what happens to MDR1 during cancer
it can be upregulated meaning it Can actively pump some drugs out of the cell, reducing intracellular concentration and meaning the drug can’t become cytotoxic
what are the two types of resistance
intrinsic or acquired
epigenetic are very resistant to what
very toxic platinum alkylating
drug resistance is influenced by what parts of the microbiome
- vascular abnormality
- hypoxia and acidity
- fibroblasts
- immune cells
- extracellular matrix
- exosomes
therapies to overcome resistance to alkylating agents
- increased delivery of platinum to the tumour
- combination of platinum drugs with molecularly targeted agents
- novel platinum drugs targeting resistance mechanism
- platinum resistance modulators
