W5 L2 - Introduction to cancer therapy Flashcards
Options for cancer treatment
- Surgery
- Radiotherapy
- Drugs
- Cell therapies
What would make a good drug target?
A good drug target is a molecule essential for disease progression, specific to the disease, accessible to drugs, and can be modified by small molecules or biologics. Examples include enzymes, receptors, and cell division proteins
Expanded hallmarks of cancer
Emerging Hallmarks
- deregulating cellular energetics
- avoiding immune destruction
Enabling Characteristics
- tumour-promoting inflammation
- genome instability and mutation
What do hallmarks of cancer lead to
uncontrolled growth of tumour cells
Chemotherapy
- Works by preventing tumour growth
- Multiple mechanisms: prevent tumour cell division
examples of chemotherapeutics
- antimetabolites
- alkylating agents
- mitotic spindle inhibitors
- topoisomerase inhibitors I and II
Alkylating agents
- type of chemotherapy drug that work by damaging the DNA of cancer cells, preventing them from growing and dividing
- Cyclophosphamide, Ifosfamide, Chlorambucil, Melphalan
Antimetabolites
a type of chemotherapy drug that interfere with DNA and RNA production, preventing cancer cells from growing and dividing. They mimic the natural building blocks of DNA but disrupt cell function when used instead.
What are mitotic spindle inhibitors
- are chemotherapy drugs that stop cancer cells from dividing by disrupting the mitotic spindle, which is necessary for cell division. They mainly target microtubules, structures that help pull chromosomes apart during mitosis.
- Vinblastine, Vincristine, Docetaxel, Paclitaxel
Topoisomerase inhibitors
- are chemotherapy drugs that block topoisomerase enzymes, which help unwind and repair DNA during cell division. By inhibiting these enzymes, the drugs cause DNA breaks, preventing cancer cells from dividing and leading to cell death
- Irinotecan, Topotecan
Targeted Therapy
treatment that uses drugs to specifically target and block molecules involved in disease growth, like cancer. Unlike traditional chemotherapy, it focuses on cancer cells while minimizing damage to healthy cells, often leading to fewer side effects. It works by targeting specific proteins or genes related to the disease
Immunotherapy
- cellular therapy, immunomodulators, oncolytic virus therapy, oncolytic virus therapy, monoclonal antibodies, cancer treatment vaccines
- treatment that uses the body’s own immune system to fight diseases like cancer. It works by boosting or modifying the immune system to recognize and attack cancer cells more effectively. This can involve using substances like antibodies, vaccines, or immune checkpoint inhibitors to enhance the immune response.
- Immunotherapy can be more targeted than traditional treatments and may have fewer side effects.
what’s cellular therapy
- transfer of human cells to replace diseased cells with healthy ones
- stem cell transplant and chimeric antigen receptor (CAR) T-cell therapy are examples of cellular therapies
immunomodulators
- medications that regulate and boost parts of the immune system.
- checkpoint inhibitors and cytokines are examples
what is oncolytic virus therapy
- lab-modified viruses that infect and kill cancer cells without harming normal cells.
what are monoclonal antibodies
- man-made proteins that attack a specific part of a cancer cell
what are cancer treatment vaccines
- medicines that train the immune system to recognise and destroy cancer cells
- unlike cancer prevention vaccines, these are designed for people who already have cancer
what’s cell therapy (T cell therapy)
- tumour or blood samples are taken
- T cells are isolated from samples
- T cells are multiplied and often their functions are enhanced
- T cells are delivered back into the patient as a living drug
- T cells continue to multiply within the patient
- T cells recognise and kill cancer cells
Side effects of cancer therapy
- Narrow therapeutic index
Particularly chemotherapy
Affects fast-dividing healthy cells - Unwanted induction of the immune system
Immunotherapy
Cell therapy
Chemotherapy Toxicities
- Common: Nausea and Vomiting, Mucositis, Gastrointestinal side effects – constipation or diarrhoea
- Acute Toxicities: Anaphylaxis, Infusion related / hypersensitivity reactions, Extravasation
- less common: Tinnitus, Renal impairment (transient or permanent), Hepatic impairment (transient or permanent)
GI side-effects of chemotherapy
- Sore mouth
- Changes in taste and smell
- Nausea and vomiting
- Changes in appetite
- Mucositis
- Diarrhoea
- Constipation
Nausea and Vomiting: cause
Nausea and vomiting involve two pathways:
- Peripheral Pathway: Triggered by irritation or toxins in the stomach or intestines, which activate receptors in the gut that send signals to the brain.
- Central Pathway: The brainstem’s vomiting center integrates signals from the chemoreceptor trigger zone (CTZ) and higher brain areas to coordinate the physical act of vomiting.
- Both pathways work together to produce nausea and vomiting.
Nausea and Vomiting: treatment
Here’s a summary of treatments for nausea and vomiting:
- Cannabinoids: Help reduce nausea, especially in chemotherapy.
- Substance P Antagonists: Block substance P to prevent nausea, used in chemotherapy.
- Antimuscarinic Drugs: Block acetylcholine to treat motion sickness and postoperative nausea.
- Antihistamines: Block histamine receptors to treat motion sickness.
- Dopamine Antagonists: Block dopamine receptors to control nausea, especially in chemotherapy and gastrointestinal conditions.
- 5HT3 Antagonists: Block serotonin receptors to prevent nausea, used in chemotherapy and surgery recovery.
Diarrhoea: cause
Diarrhea can be caused by a variety of factors, including:
- Infections:
Bacterial: Infections from bacteria like Salmonella, E. coli, or Campylobacter.
Viral: Viruses such as norovirus or rotavirus.
Parasitic: Parasites like Giardia or Entamoeba histolytica.
- Food and Drink:
Food intolerances: Such as lactose intolerance.
Food poisoning: Consumption of contaminated food or water.
Excessive alcohol or caffeine: These can irritate the digestive system.
- Medications:
Antibiotics, antacids containing magnesium, or other drugs can disrupt normal gut function.
Inflammatory Conditions:
Irritable Bowel Syndrome (IBS).
Inflammatory Bowel Disease (IBD) like Crohn’s disease or ulcerative colitis.
- Digestive Disorders:
Disorders like celiac disease or pancreatic insufficiency.
Stress and Anxiety:
Psychological factors can affect the gut, causing diarrhea.
- Dietary Factors:
High-fat or spicy foods can irritate the intestines.
- Hormonal Imbalances:
Conditions like hyperthyroidism or certain infections that alter hormone levels can lead to diarrhea.
Mucositis: cause
Mucositis is inflammation of the mucous membranes and can be caused by:
Cancer treatments: Chemotherapy and radiation damage the mucosal lining.
Infections: Viral, bacterial, or fungal infections can lead to mucositis.
Medications: Certain drugs, like NSAIDs or antibiotics, may cause irritation.
Autoimmune disorders: Conditions like lupus or pemphigus vulgaris.
Nutritional deficiencies: Lack of vitamins like B12 or folic acid.
Physical irritation: Smoking, alcohol, or dental trauma.
Diarrhoea and mucositis: treatment
- Antibiotics
- Pro-biotics
- Anti-oxidants
- Mucosal barrier regulators
- Anti-inflammatories
- Hormones
- Pain killers
- Nutrition replacement
Side-effects of immunotherapy
- colitis
- AKI
- myocarditis
- vomiting
- hepatitis
Why haven’t we cured cancer yet?
- Dose limiting side effects of drugs
- Think about the biology of cancer
Mutations
Evolution
Tumour microenvironment - Extrinsic factors
Discovery and diagnosis
Access to health care
Available drugs
Health economics
Dose Modification Immunotherapy
Adverse Reactions: If a patient develops severe side effects, the dose may be reduced or treatment may be temporarily paused until the patient recovers.
Organ Toxicity: Immunotherapy can cause inflammation or damage to organs like the lungs, liver, or kidneys. Dose adjustments are made if such toxicities occur.
Disease Progression: If a patient’s cancer shows no improvement or worsens, the dose may be increased or a different immunotherapy drug may be chosen.
Patient Health Status: Adjustments are also made depending on the patient’s overall health, including factors like age, immune function, and comorbid conditions.
In summary, dose modification in immunotherapy aims to balance the effectiveness of the treatment with the patient’s ability to tolerate it.
