Chemotherapy drugs Flashcards
What is cancer?
When a normal cell undergoes uncontrolled proliferation to become a malignant tumour.
Compared to benign tumours what is a malignant tumour?
One that causes the cells to have loss of function, it is invasive and has the ability to metastasize and go from one location to another. A benign tumour lacks invasive properties and is unable to metastasize.
What are some of the causes of cancer?
DNA mutations that are either inherited or acquired.
Give an example of an inherited DNA mutation
Defective BRCA1/2 gene which causes breast cancer.
Deficiencies in DNA repair enzymes
Give examples of acquired DNA mutations
Viruses (HPV - cervical cancer), carcinogens (asbestos, smoking & radiation), alcohol, drugs, sun exposure, geographical location.
How is cell growth normally regulated?
Growth factors, cell cycle transducers, apoptotic genes & telomeres
What are proto-oncogenes?
Proteins that increase cell division, decrease differentiation and decrease cell death
What are oncogenes?
Proteins that increase cell division and promote cell survival, leading to cancer.
If a gene mutation occurs in the promoter region, what happens?
There’s an increase in transcription
What happens when a gene mutation causes gene amplification ?
More copies of the proto-oncogene are made
What is chromosome translocation?
Where a bit of a chromosome containing proto-oncogenes is moved to a new site where protein expression is more likely to occur and can lead to cancer
What can happen when a proto-oncogene fuses with another gene?
Can make a protein that has more activity
What happens during metastasis?
When a primary tumour produces enzymes that break down ECM (extracellular matrix), which allows cells to then invade nearby tissues and causes growth of new blood vessels (angiogenesis). Cells are then transported via blood or lymphatic vessels to cause a secondary tumour.
What are the main types of cancer treatments?
Surgery to remove solid tumours, radiotherapy, chemotherapy or a combination of the 3.
What are the aims of chemotherapy?
Kill all malignant cells
After chemotherapy, we cannot rely on the immune system to kill the rest, why not?
Immune system can’t recognise the cancer cells are they are too similar to normal cells.
Toxic effects of chemotherapy
Suppression of bone marrow (which makes RBC's & WBC's) Impaired wound healing Loss of hair Damage to GI tract Stunted growth in children Can cause problems with reproduction Teratogenicity Nausea & Vomiting
What are the 4 main classes of anti cancer drugs?
Cytotoxic, Hormones, Monoclonal antibodies & Protein kinase inhibitors
How do cytotoxic drugs work as anti cancer drugs?
By blocking DNA synthesis and preventing cell division
How do hormones work as anti cancer drugs?
They suppress opposing hormone secretion or inhibit actions of hormones
How do monoclonal antibodies work as anti cancer drugs?
By targeting specific cancer cells
How do protein kinase inhibitors work as anti cancer drugs?
By blocking cell signalling pathways in rapidly dividing cells
What is an alkylating agent?
A cytotoxic anti cancer drug
what do alkylating agents do?
Target cells in S phase of cell cycle and form crosslinks with DNA (covalent bonds) to prevent uncoiling of the DNA strands thus inhibiting replication
What are the side effects of prolonged use of alkylating agents?
Sterility and an increased risk of developing non-lymphocytic leukaemia
What are the 3 main classes of alkylating agents?
Nitrogen mustards, nitrosoureas and platinum compounds
Cyclophosphamide, melphalan, chlorambucil, bendamustine and estramustine are examples of…
Alkylating agents - Nitrogen mustards
Only given via IV.
What nitrogen mustard can be used in the treatment of prostate cancer?
Estramustine
Nitrosoureas’ are highly lipophilic meaning they can do what?
Cross the blood brain barrier and be useful in treating CNS cancers
Camustine and lomustine are examples of….
Alkylating agents - Nitrosoureas
Cisplatin, carboplatin and oxaliplatin are an example of…
Alkylating agent - Platinum compounds
Which types of cancer can be treated by the platinum compound drug cisplatin? Why?
Testicular and ovarian because they have low levels of repair enzymes
Side effects of platinum compound drug cisplatin?
Nephrotoxicity requiring hydration, nausea and vomiting and increased risk of tinnitus, peripheral neuropathy, hyperuricaemia and anaphylaxis.
The alkylating agent busulfan is a selective drug for bone marrow and is used as a treatment for which type of cancer?
Leukaemia
What does the alkylating agent procarbazine treat and what are the side effects?
Treats Hodgkin’s disease. SE’s of hypersensitivity rashes and inhibition of MonoAmineOxidase (breaks down neurotransmitters)
What cancers does the alkylating agent trabectedin treat and what are the side effects?
Treats soft tissue sarcoma and advanced ovarian cancer. SE’s of hepatotoxic
What is methotrexate?
An antimetabolite (folate antagonist) that inhibits dihydrofolate reductase (an enzyme that plays a part in DNA synthesis & division)
Fluorouracil, capecitabin, cytarabine and gemcitabine are examples of…
Antimetabolites (pyrimidine analogues)
How do Pyrimidine analogues work in the treatment of cancer?
Compete with C & T bases which make up RNA & DNA and essentially inhibit DNA synthesis
Mercaptopurine, tioguanine, pentostatin and fludarabine are examples of…
Antimetabolites (purine analogues)
How do Purine analogues work?
By competing with A &G bases to inhibit purine metabolism
What is doxorubicin? How does it work as an anti cancer drug?
Its a cytotoxic antibiotic that binds to DNA and inhibits DNA/RNA synthesis. Also inhibits topoisomerase II.
What is bleomycin?
A cytotoxic antibiotic that works by degrading pre-formed DNA.
Vincristine, vinblastine & vindesine are examples of…
Vinca alkaloids (from plant derivatives)
How do vinca alkaloids work?
Prevention of spindle formation in mitosis.
Taxanes such as paclitaxel and docetacel treat what kinds of cancer?
Breast cancer & ovarian cancer
Etoposide a derivative of mandrake root is used in the treatment of which cancers?
Testicular and lymphomas.
Hormones are used in the treatment of what kinds of cancer?
Cancers in tissues which are sensitive to hormones e.g. breast, prostate and ovaries.
How do oestrogens (ethinyloestradiol & diethylstilbestrol) work?
They are antagonists of androgen-dependent prostate cancer.
Side effects of oestrogens (ethinyloestradiol & diethylstilbestrol)
Nausea, fluid retention, thrombosis, impotence and gynaecomastia.
Progestogens such as megestrol, medroxyprogesterone & norethisterone can be used in the treatment of which cancers?
Endometrial and breast cancer
GnRH analogues such as goserelin, buserelin, leuprorelin and triptorelin are used in the treatments of which cancers?
Prostate and advanced breast cancer.
Somatostatin analogues such as octreotide and lanreotide can be used in the treatment of which cancers?
Hormone secreting tumour of the GI tract
Hormone antagonists & what they treat.
Tamoxifen treats breast cancer.
Flutamide, cyproterone and bicalutamide treat prostate cancer.
Glucocorticoids prednisolone and dexamethasone can be used in the treatments of which types of cancers?
Lymphomas and leukaemias
Immunotherapy uses…
Monoclonal antibodies
How does immunotherapy work?
Drugs react with target proteins on cancer cells activating the immune system to cause lysis of cancer cells
Rituximab, a monoclonal antibody treats which cancers?
Lymphoma
Herceptin (trastuzumab) is used in the treatment of breast cancer, how does it work?
Side effects?
Binds to HER2 (found in 25% of breast cancers) and induces an immune response and induces cell cycle inhibitors.
Side effects of tremor, flu, itchy eyes, BP changes and palpitations.
Imatnib is a protein kinase inhibitor, what cancers does it treat?
Chronic myeloid leukaemia
Give an example of a drug that can be used to treat the side effect of nausea and vomiting with cancer treatments.
Ondansetron, granisetron & metoclopramide
Give an example of a drug that can be used to treat anxiety due to cancer treatment
Lorazepam (benzodiazepine)
