Notes in 1- Cancer

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Published	02/10/2024	{{c1::Cancer}} is a disease of the genome occuring as a result of unregulated cell growth
Published	02/10/2024	Types of Cancer Cells:[1] {{c1::Epithelial}} Cells[2] {{c1::Mesoderm}} Cells[3] {{c1::Glandular}} Cells
Published	02/10/2024	The Hallmarks of Cancer:
Published	02/10/2024	Mention some Hallmarks of Cancer
Published	02/10/2024	Sustaining Proliferative SignallingGrowth signal {{c1::automony}} = lack of regulation of growth factor signallingNormal cells require an external gro…
Published	02/10/2024	A {{c1::mutation}} is any change in DNA sequence of a cell.
Published	02/10/2024	{{c1::Inhibitory growth signals}} are signals that maintain homeostasis within the tissue.→ as a result, cells are not continously dividing Cance…
Published	02/10/2024	{{c1::Gene silencing}} is the interruption or suppression of gene expression at transcriptional or translational level.
Published	02/10/2024	Why are normal cells not continously dividing like cancer cells?
Published	02/10/2024	Some cancer cells are able to avoid immune system detectionby not initiating an immune response.Via:- Hijacking {{c1::immune checkpoints}}- Modulating…
Published	02/10/2024	An {{c1::immune checkpoint}} is a built in control mechanism that maintains self tolerance during an immune response.Immunotherapy drugs target these …
Published	02/10/2024	Normal cells have a counting device that monitors and adjusts the number of cell doublings, it is known as a {{c1::telomere}}Once cell numbers ha…
Published	02/10/2024	Why do cancer cells have unlimited replicative potential?
Published	02/10/2024	- All tumours have inflammatory immune cells→ provide growth factors that promote {{c1::angiogenesis}} and {{c1::invasion}}- Cell death by necrosis gi…
Published	02/10/2024	Why do all tumours have inflammatory immune cells?
Published	02/10/2024	How does cell death by necrosis give rise to inflammation and mutations?
Published	02/10/2024	{{c1::Invasion and Metastasis}} is a hallmark of malignant cancer characterized by the ability to migrate to other areas.→ major cause of death i…
Published	02/10/2024	{{c1::Angiogenesis}} is the creation of new blood vessels by the tumour→ provides supply of oxygen and nutrients→ 'friable' blood vessels may lead to …
Published	02/10/2024	- Alterations in DNA lead to instability - Faulty DNA repair pathways or hereditary predisposition contribute to the development of mutations- Si…
Published	02/10/2024	Why is cancer more frequent in the ageing population?
Published	02/10/2024	Normal cells undergo cell death in response to extracellular factors or physical damage.Cell death is either:[1] {{c1::Apoptosis}} - regulated, progra…
Published	02/10/2024	Cancer cells evade death as a result of {{c1::mutations}} within the apoptosis pathwaye.g. {{c1::mutations}} in Caspase family→ Caspases play a centra…
Published	02/10/2024	{{c1::Aerobic Glycolysis}} is used by cancer cells to redirect energy.→ produces intermediates that can be used in the biosynthetic pathways.→ allows …
Published	02/10/2024	{{c1::Reprogramming Energy Metabolism}} refers to the ability of cancer cells to alter their metabolism in order to support the increased&nb…
Published	02/10/2024	{{c1::Somatic}} mutations → most common & acquired{{c1::Germline}} mutations → hereditary
Published	02/10/2024	{{c1::Oncogenes}} are mutated genes that give rise to tumour formation in a dominant fashion.{{c1::Tumour suppressor genes}} are genes that inhibit tu…
Published	02/10/2024	What is the significance behind mutations in Tumour Suppressor Genes being recessive?
Published	02/10/2024	{{c1::Haploinsufficiency}} is when one mutated allele can lead to cancer rather than two.
Published	02/10/2024	The Cell Cycle:Interphase:{{c1::G1}} → cells grow larger and copy organelles{{c1::S}} → complete copy of DNA{{c1::G2}} → further cell growth…
Published	02/10/2024	Organs are well-defined by {{c1::basement membranes}} which are made up of extracellular matrix proteins (collagen & proteoglycans).Theories …
Published	02/10/2024	The {{c1::Extracellular Matrix (ECM)}} is a complex meshwork of proteins and carbohydrates.Features:[1] Made up of collagen/proteoglycans → gives…
Published	02/10/2024	• {{c1::Cadherins}} are a type of cell adhesion molecule (CAM)→ these bind cells to each other and the ECM • {{c2::E-cadherin}} is involved in ce…
Published	02/10/2024	Mechanisms of Metastasis:[1] {{c1::Monoclonal}}[2] {{c1::Polyclonal}}Two patterns → Linear & Branched---------Subclonal → spread of tumour cells f…
Published	02/10/2024	{{c1::Epithelial Mesenchymal Transition (EMT)}} is the process of closely connected epithelial cells becoming independent mesenchymal cells with the a…
Published	02/10/2024	{{c1::Mesenchymal cells}} are stem cells found in bone marrow.
Published	02/10/2024	Journey to Metastasis[1] {{c1::Invasion}}[2] {{c1::Intravasation}}[3] {{c1::Transport}}[4] {{c1::Extravasation}}[5] {{c1::Colonisa…
Published	02/10/2024	Journey to Metastasis: [1] {{c1::Invasion}}EMT begins with signals from tumour stroma (HGF, TGF-beta) stimulates kinase receptors (EGFR) &am…
Published	02/10/2024	Journey to Metastasis: [2] {{c1::Intravasation}}→ Entry into blood or lymphatics• Tumour cell attaches to stromal side of basement membrane …
Published	02/10/2024	Journey to Metastasis: [3] {{c1::Transport}}Tumour cells in bloodstream = circulating tumour cells (CTCs) • Solo travellers vs. Clumps → uni…
Published	02/10/2024	Journey to Metastasis: [4] {{c1::Extravasation}}Exit of tumour cells from bloods vessels into distant tissues • Tumour cells become trapped …
Published	02/10/2024	Journey to Metastasis: [5] {{c1::Colonisation}}Site of metastasis is determined by the {{c2::point of extravasation}} and the {{c2::microenv…
Published	02/10/2024	{{c1::Angiogenesis}} is the formation of new blood vessels.Angiogenic switch is dependent on the inhibitors and inducers.Balance between inhibitors an…
Published	02/10/2024	{{c1::Angiogenic Inducers}} are pro-angiogenic factors or drugs that stimulate angiogenesis.VEGF (Vascular Endothelial Growth Factor) is the most rele…
Published	02/10/2024	{{c1::Angiogenic Inhibitors}} are anti-angiogenesis factors or drugs that inhibit angiogenesis. (off-switch)• Plasminogen is cleaved to form Angi…
Published	02/10/2024	{{c1::Concomitant resistance}} - enables growth in distant metastases that were previously dormant when a tumour is removed by surgery or radiation.Th…
Published	02/10/2024	{{c1::Chemotherapy}} is a combination of compounds that target DNA, RNA & Proteins to interrupt the cell cycle of rapidly growing and dividing can…
Published	02/10/2024	Why does chemotherapy cause hair loss?
Published	02/10/2024	{{c1::Neoadjuvant}} chemotherapy - given before surgery to reduce cancer size{{c1::Adjuvant}} chemotherapy - reduce risk of cancer returning{{c1::Dise…
Published	02/10/2024	Types of Chemotherapy:[1] {{c1::Alkylating agents}} and {{c1::Platinum drugs}}→ forms DNA adducts blocking DNA replication (acts on all phases of…
Published	02/10/2024	{{c1::Alkylating agents}} and {{c1::Platinum drugs}} is a type of chemotherapy characterized by the formation of DNA adducts blocking DNA re…
Published	02/10/2024	{{c1::Antimetabolites}} is a type of chemotherapy that structurally mimics essential molecules required for cell division (acts on S phase o…
Published	02/10/2024	Organic drugs are a type of chemotherapy that includes:[1] {{c1::Vinca Alkaloids}}→ bind to tubulin and prevent microtubule assembly (essential i…
Published	02/10/2024	Side effects of chemotherapy:70% - nausea/vomiting
Published	02/10/2024	Personalised Systemic Therapies:[1] {{c1::Hormonal Therapy}}Anti-oestrogen, Aromatase inhibitors[2] {{c1::Targeted Therapy}}EGFR, VEGF, CDK 4/6[3] {{c…
Published	02/10/2024	Hormonal Therapy e.g. Breast CancerOestrogens (estradiol/esterone) play major role in triggering breast cancerOestrogens promote cell proliferati…
Published	02/10/2024	Targeted Therapy→ EGF receptor signalling pathway(Transmission of growth signals from ECF to ICF)Usage of EGFR inhibitors
Published	02/10/2024	{{c1::EGFR inhibitors}} are substances that block the activity of a protein called epidermal growth factor receptor (EGFR)e.g. Tyrosine Kinase Inhibit…
Published	02/10/2024	{{c1::CDK 4/6 inhibitors}} are molecules that block the progression of cells through the cell cycle by inhibiting cyclin dependent kinase (CDK).C…
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Published	02/10/2024	{{c1::Immunotherapy}} is a therapy that involves the immune system, a complex network protecting body from harm.Cells derived from {{c1::haematopoieti…
Published	02/10/2024	{{c1::Immune checkpoints}} are the brakes of the immune system that ensure that self tolerance is maintained, they are inhibitory by nature.Activated …
Published	02/10/2024	Immunotherapy - Therapeutic agents{{c1::Pembrolizumab}} - IgG4 monoclonal antibody (KEYTRUDA)Normal Immune response:Activation of T-cells → attack tum…
Published	02/10/2024	How does Pembrolizumab (KEYTRUDA) cause T-cell reactivation and restoration of the immune's system function?
Published	02/10/2024	Indications in Scotland:
Published	02/10/2024	Immunotherapy - Side Effects:
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