Oncology and Pathology Flashcards
Which Tumours like to travel to the bone?
lung
breast
prostate
ovary
Which tumors metastasis to everywhere in the body?
melanoma
kidney
thyroid
Which bones do tumour mainly metastasis to?
Spine!!!,
Pelvis,
Femur,
Humerus,
Ribs,
Skull
What are the names of cancers based on their tissue origin?
Epithelial cells →
Mesoderm cells →
Glandular cells →
Epithelial cells → Carcinomas
Mesoderm cells → Sarcomas
Glandular cells → Adenocarcinomas
What are the exposures/ factors that lead to cancer
- Radiation
- Ageing
- Pollution
- Environment
- Diseases (COPD)
- Genetics
- Occupation
- Asbestos
- Tobacco
- second hand smoke
What are the hallmarks of cancer cell behaviour?
- Avoid immune destruction
- Unlimited replicative potential
- Tumour promoting inflammation
- Invasion and metastasis
- Angiogenesis
- Genome instability and mutation enabling
- Evasion of cell death - limited response to apoptotic signals
- Reprogramming energy metabolism
- Growth signal autonomy - do not need GF signaling to divide
- Evasion of growth inhibitory signals
Explain the normal activation of transmembrane Tyrosine Kinases receptors?
- they are involved in mediating cell-to-cell communication and controlling various biological functions
- they ae activated by receptor-specific ligands - dimerization’s results in down stream transmembrane conformational changes placing the tyrosine kinase in an ‘active’ confirmation
- mutations in tyrosine kinase receptors can drive uncontrolled cell growth
What are the two ways Tyrosine Kinase Receptors can be dysregulated?
- ligand-_dependent_ firing mutating to ligand-_independent_ firing (firing without a catalyst)
- receptor remains the same however has autocrine signaling/ activation (produces ligand to activate itself)
lung ,breast ,bladder, AML, gastro mutations respectively
What Tyrosine Kinase Growth Factor receptors are altered in human tumours?
-
EGF-R/ErbB1/HER1
- overexpression → non-small cell lung cancer, breast, head and neck, stomach, colorectal, esophageal, prostate, bladder, renal, pancreatic and ovarian carcinomas, glioblastomas
- truncation of ectodomain → glioblastoma, lung and breast carcinoma
-
ErbB2/HER2/Neu
- overexpression → 30% of breast adenocarcinomas
-
FGF-R3
- overexpression; amino acid substitutions→ multiple myeloma, bladder and cervical carcinomas
-
FLT-3
- tandem duplication → acute myelogenous leukemia (AML)
-
Kit
- amino acid substitution → gastrointestinal stromal tumour
breast and lung, colorectacl, lung, neuro and prostate, ovarian
Give examples of receptors making autocrine growth factors and what Human tumours they present in?
- c-Met: when bound with it’s ligand HGF (hepatocyte growth factor) ligand → miscellaneous endocrinal tumours, invasive breast and lung cancers, osteosarcoma
- IGF-1R: IGF-2 ligand → colorectal
- EGF-R: TGF-∝ ligand → squamous cell lung, breast and prostate adenocarcinoma, pancreatic, mesothelioma
- VEGF-R (Flt-1): VEGF-A ligand → neuroblastoma, prostate cancer, Kaposi’s sarcoma
- ErbB2 (HER2 or NEU)/ErbB3: NRG ligand → Ovarian carcinoma
What are the therapeutic options for the following hallmarks of cancer?
what is the treatment strategies in cancers that have an EGFR mutation?
- EGFR- Tyrosine kinase inhibitors - Afatinib
- Anti-EGFR antibody inhibitors
What is a common mechanism of resistance to Tyrosine Kinase Inhibitors?
T790M mutations in the gene that codes for EGFR (epidermal growth factor receptor). This increases the affinity for ATP
- 60% of progressive disease is due to the T790M mutation
What are risk factor for developing breast cancer?
● Female (99% of breast cancers)
● Increased oestrogen exposure (earlier onset of periods and later menopause)
● More dense breast tissue (more glandular tissue)
● Obesity
● Smoking
● Family history (first-degree relatives)
● Combined contraceptive pill gives a small increase in the risk of BC, but returns to normal ten years after stopping the pill
● HRT increases the risk of BC particularly the combined HRT containing both oestrogen and progesterone
How do cancers occur?
- Oncogenesis is a multistage process, cells accumulate damage in several important genes related to mitosis/ cell differentiation
- most mutations acquired in our somatic cells
- some cancers inherited due to mutations in the germline
Give an example of an inherited mutation in an Oncogene
- what does it cause?
RET oncogene (MEN2A - Multiple endocrine neoplasia type 2)
- Parathyroid cancer
- Pheochromocytoma
- Medullary thyroid cancer
Give an overview and epidemiological background of Multiple Endocrine Neoplasia type 2 (MEN2)
- inherited autosomal dominant
- occurs in 1:40,000
- RET proto-oncogene codes for tyrosine kinase receptor
- should be suspected when ≥ 2 endocrine tumour occur together
- 95% of people with genetic variant will present with medullary thyroid cancer
- Pheochromocytoma occurs in 50%
- Hyperparathyroidism in 20-30% of those with the variant
How would a person with MEN2A present clinically?
- Medullary thyroid cancer
- mass or lump in in neck, may be painful
- Cushing syndrome
- facial flushing
- Excess hormone production from
- pheochromocytomas (adrenals)
- High blood pressure
- glucose intolerance
- pallor and vasoconstriction
- and/or adenomas in parathyroid glands
- pheochromocytomas (adrenals)
- with symptoms of these diseases
- bone pain due to metastasis
- weight loss
- severe diarrhea (due to calcitonin and hormones released)
