Chemotherapy & Immunotherapy Flashcards
how can chemotherapy be classified?
- Classification by cell cycle preference
- Classification by chemical properties
what are the stages of the cell cycle and which stages to cell-cycle specific and non cell-cycle specific chemotherapy drugs act on?
G0 phase: Undivided cell
G1 phase: Duplication of cellular content. Cellular growth
S phase: DNA replication
G2 phase: Further cell growth
M phase: Cell division
cell cycle specific = G1, S, G2, M not G0
cell cycle non specific = all stages
what are some classes of cell cycle specific chemotherapy drugs?
taxanes
vinca alkaloids
antimetabolites
topoisomerase inhibitors
what are some classes of cell cycle non-specific chemotherapy drugs?
alkylating agents (busulfan, cyclophosphamide)
platinum analogs (carboplatin, cisplatin)
anthracyclines
what are alkylating agents?
Bind covalently via alkyl groups to DNA making cross-linking between the DNA strands preventing the DNA from replication
what are platinum agents?
They bind covalently to the DNA forming cross-links preventing the DNA from replication.
eg cisplatin, carboplatin, oxaliplatin
what are antimetabolites?
They have a similar structure to normal metabolites which are required for DNA synthesis.
They affect DNA synthesis by acting as a substitute to the actual metabolites that would be used in the normal metabolism
what are topisomerase inhibitors?
- Topoisomerase is an enzyme that cuts one or both straps of the DNA to prevent the overwinding during DNA replication.
- Topoisomerase 1: cuts one strand of the DNA
- Topoisomerase 2 : cuts both strands off the DNA
what are tubulin active agents?
Bind to tubulin and prevent the formation of mitosis spindles which are crucial for chromosome separation during cell division.
eg
Vinca Alkaloids: Vinblastine, vincristine, vinorelbine
Taxanes: docetaxel, paclitaxel
Epothelones: Eribulin
what are some immediate side effects of chemotherapy?
- extravasation - leakage of chemotherapy to the adjacent tissue
- facial/body flushing
- cardiac arrhythmias
- hypotension
- hypersensitivity
- anaphylaxis
- haemorrhagic cysts
what are some short to medium term side effects of chemotherapy?
- Discoloration of urine
- Tumour lysis syndrome
- Nausea and vomiting
- Mucositis
- Constipation
- Diarrhoea
- Fatigue
what are some medium to long term side effects of chemotherapy?
- Bone Marrow suppression
- Alopecia
- Liver dysfunction
- Renal toxicity
- Cardiac toxicity
- Peripheral neuropathy
- Pulmonary Fibrosis
- Changes in fertility
describe how chemotherapy can become resistant
Cancer cell can develop many resistance mechanisms to chemotherapy drugs:
- Cancer cells limit chemotherapy drugs accumulation by modifying their membrane composition.
- Reducing drug transporters
- Increasing efflux pumps
- Developing detoxification mechanisms lead to drug inactivation
- Drug target modification or loss
- Sophisticated DNA repair system and upregulation of prosurvival genes
what are the 5 categories of immunotherapy?
- Checkpoint inhibitors
- Adoptive cell therapy
- Cancer vaccines
- Cytokines
- Oncolytic virus therapy
what are check point inhibitors?
Check points are receptors on the surface of T cell. They suppress the T cell immune response to prevent T cells from attacking normal cells.
Types:
- PDL1 receptor inhibitors
- PD1 receptor inhibitors
- CTLA-4 receptor inhibitors
what is adoptive cell therapy?
- T cells are isolated from the patients. Modification and multiplication of those cells in the laboratory and then re-injection back to the patient circulation
- CAR-T – chimeric antigen receptor T-cell – therapy
- Very expensive! One session = £280000
- Licensed in the UK for B cell CLL and lymphoma (DLBCL)
what are cancer vaccines?
- Sipuleucel-T is the first human cancer treatment vaccine to receive FDA approval. The treatment is personalised , using a patient’s own dendritic to create an immunostimulatory vaccine.
- Licensed for metastatic prostate cancer.
what are cytokines?
- They are small proteins naturally produced and secreted by several immune system cells. They are crucial in signaling between immune cells, as well as between immune cells and several other cell types in the body
- Interleukin 2 (IL-2) is the only cytokine licenced to treat cancer (Kidney and melanoma)
what is oncolytic virus therapy?
- Viruses target particular cancer. The virus will infect the cancer cell and replicate itself. This results in destruction of the cancer cell, releasing the tumour antigens and activating antibodies. T-cells will be activated and generates antitumor response causing the cancer cell to die
- T-VEC is an intra-lesionally delivered vaccine, contains a genetically engineered herpes simplex virus type 1 (HSV-1) that selectively replicates in tumour, lyses tumour cells, while promoting antitumor immunity. It is licenced in melanoma.
what are the side effects of immunotherapy?
