Cancer Therapy Flashcards
Properties of cancer
Self-sufficiency in growth signals Insensitivity to anti-growth signals Tissue invasion and metastasises Evading apoptosis Sustained angiogenesis Limitless replicative potential
Types of cancer therapy
Neoadjuvant - administered before definitive treatment (surgery or radiotherapy) to shrink tumour and optimise outcomes
Adjuvant - given after treatment to reduce risk of disease recurrence
Palliative - designed to relive symptoms and improve quality of life
Options of cancer treatment
Traditional - chemotherapy - radiotherapy - surgery Novel therapies - immunotherapy - monoclonal antibodies - checkpoint inhibitors - radioimmunotherapy - drugs targeting oncogenes - signal transduction inhibitors - anti-apoptotic agents
Principles of chemotherapy
Treatment of cancer with drug therapy
Interfere with essential step required for cell growth and proliferation
Damaged cancer cell unable to repair damage and initiate programmed cell death - apoptosis
Mechanisms of cancer cell resitance
Decrease uptake of drug Increase drug metabolism After drug targets Impair apoptotic pathway After cell cycle checkpoints Efflux pumps
Side effects of chemotherapy
Brain - chemo-brain - peripheral neuropathy - fatigue Hair - alopecia Heart/blood - neutropenic sepsis - cardiomyopathy - myelosuppression -> bleeding from low platelets, fatigue from anaemia and sepsis GI - vomiting - mucositis - diarrhoea - constipation Bladder - haemorrhagic cystitis Skin - PPE - rash - nail ridging/loss Reproductive organs - impaired fertility - decreased libido - premature menopause Kidneys - AKI - electrolyte disturbances Liver - deranged LFTs Lungs - pneumonitis - PE
Anti-emetics for chemotherapy
5HT receptor antagonists - ondansetron
- block receptors in GI tract and CNS tract
Dopamine receptor antagonist - metoclopramide
- act centrally by blocking the chemoreceptor trigger zone
Steroids - dexamethasone
Antihistamines - cyclizine
NK1 receptor antagonists - aprepitant
Antimuscarinics - hyoscine
Cannabinoids - nabilone
Benzodiazepines - midazolam, lorazepam
Features of tumour lysis syndrome
Tumour cell lysis -> hyperkalaemia
Release of DNA, phosphorus leads to Ca-Phos precipitation -> hypocalcaemia leading to arrhythmias
-> urate and Ca-Phos nephropathy
Release of purines, hypoxanthine, uric acid
- needs IV fluids, allopurinol and rasburicase
Features of immunotherapy
Uses immune system and its components to recognise, target and destroy cancer cells
Passive
- ex vivo
- activated cells or molecules that once found inside body compensate for missing or deficient immune functions
Active
- stimulates effector functions in vivo
- requires patient’s immune system to be able to respond upon challenge, stimulated and mediate effector functions
Types of immunotherapy
Passive - tumour-specific mAbs - cytokines - adoptive cell transfer Active - oncolytic viruses - checkpoint inhibitors - allogeneic whole cell vaccines - DC vaccines
Features of monoclonal antibodies
Bind to a certain antigen on cancer cell surface, blocking specific downstream signalling pathways and arresting cell proliferation
- HER2 inhibitors - Herceptin (Trastuzumab) in breast and gastric cancers
- VEGR (vascular epithelial growth receptor ) inhibitors - Bevacizumab in ovarian and bowel cancer
- EGFR inhibitor (epithelial growth factor receptor) - Cetuximab/Panitumumab in bowel cancer
Side effects of targeted therapies
Skin toxicity - acneform rash - dry skin Hair growth disorders Pruritis Nail changes Fatigue Myelosuppression Diarrhoea Nausea Hypertension Proteinuria GI perforation Delayed wound healing Arterial thromboembolic events Cardiac ischaemia Flu-like symptoms Abnormal LFTs Allergic reaction
Features of checkpoint inhibitors
Can be used as single agents or in combination
CTLA4 inhibitor
- Imipilumumab - used in melanoma
PD-1/PD-LI inhibitors
- Nivolumab, Pembrolizumab used in melanoma, lung and renal cancers
Features of side effects of checkpoint inhibitors
Inflammatory adverse reactions
Increased/excessive immune activity
Can present months following last dose
Most resolve after prompt therapy or withdrawal
Corticosteroids or alternate immunosuppression led to reversal in majority
Side effects of checkpoint inhibitors
GI - diarrhoea - abdo pain - blood or mucus in stool - bowel perforation - peritoneal signs - ileus Skin - immune-related dermatitis - pruritus - dry skin - rash - Stevens-Johnson syndrome or toxic epidermal necrolysis Hepatic - immune related hepatitis - symptoms of hepatotoxicity Neuro - immune-related neuropathies - unilateral or bilateral weakness - sensory alterations - paresthesia - myasthenia gravis - Guillain-Barre syndrome Endocrine - hypophysitis - hypopituitarism - adrenal insufficiency - hypothyroidism Other - eosinophilia - angiopathy - myocarditis - temporal arteritis - vasculitis - blepharitis - conjunctivitis - episcleritis - uveitis - arthritis - polymyalgia rheumatica - nephritis - haemolytic anaemia - pneumonitis