Cancer Flashcards
What are the 6 hallmarks of Cancer
Mnemonic SILENT (6)
S - Self sufficiency in growth signals: can be caused by increased exposure to growth factor, mutation to keep GH response pathway ‘on’ or increased GH expression in cell.
I - Insensitive to growth inhibition signals: caused by loss of function to tumour suppressor gene e.g p53, RB.
L - Limitless replication potential: Telomerase activation which maintains Telomeres, preventing eventual cell division limit.
E - Evasion of Apoptosis: Gain of function of genes preventing apoptosis (BCL2) or Loss of function of genes promoting apoptosis (BAX or P53).
N - Neo-angiogenesis: Typically requires tumour to produce Vascular endothelial growth factor.
T - Tissue Invasion and metastasis: aided by Neoangiogenesis.
What are enabling characteristics of Cancer? (2)
Mnemoic: GT
- Genomic instability and mutation
2. Tumour promoting inflammation: immune response increases proliferation and resistance to cell death.
What are the emerging hallmarks of cancer? (2)
Mnemonic: AA
- Altered cellular energetically
2. Avoidance of immune cell recognition and destruction
What are:
Oncogene
Tumour suppressor gene
Proto-oncogene
Mutator gene (4)
- Oncogene - A gene that has gained function mutation for positive regulation of growth. These mutations are dominant (only needs 1 allele).
- Tumour suppressor gene - A gene that has lost function mutation for negative gene regulation. Mutation is recessive.
- Proto-oncogene: A ‘wild type’ (unmutated) gene involved in positive growth regulation. Can become oncogene if mutated.
- Mutator Genes: Involved in DNA repair. If they become mutated or deleted increases mutation.
How does Chronic Myeloid Leukemia occur?
What drugs treats it? (3)
It is caused by translocation between chromosome 9 and 22.
This causes unique tyrosine kinase BCR-ABL to be formed.
Imatinib is a drug that can successfully selectively inhibit action of BCR-ABL kinase.
Over expression of Human Epidermal Growth Factor 2 (HER2) is a mutation in 15-30% of invasive breast cancer.
What drugs are used to treat this? How do they work? (3)
- Trastuzumab (blocks downstream signalling). Can also be used as antibody drug conjugate, as it has been linked to microtubule inhibitor DM1.
- Pertuzumab (blocks dimerisation of HER2)
What are 2 ways CLL diagnosed? (2)
What are the characteristics in patients with advanced CLL? (2)
- Routine full blood count which shows raised white blood cell count.
- Definitive diagnosis is made using Cyrometry. This checks for CD5 and CD19 antigens on clonally expanded B cells.
- 25-50% of patients are asymptomatic. In advanced disease patients show enlarged lymph nodes, anaemia and bruising due to low red blood cell and platelet count.
- Blood film show characteristic smudge cells due to damage to white blood cells.
What are the 3 stages in Binet Staging System in prognosis of CLL (3)
Clinical staging: Binet Staging System.
Stage A: Confirmed CLL due to CD5/CD19 lymphocytes >5x10^9/L
Stage B: At least 3 areas of palpable lymphoid tissue enlargement
Stage C: Haemoglobin or Platelet count <100g/L (shows bone marrow failure)
What are the prognostic markers in early stage Patients still in stage A? (4)
- Lymphocyte Doubling time (LDT): if short shows poor prognosis.
- Immunoglobulin heavy chain gene mutation status (IGHV): If unmutated shows poor prognosis.
- CD38 and CD49d: If high cell surface expression then poor prognosis
- p53 deletion/mutation = poor prognosis
What are the standard treatment options for patients with CLL:
For fit patients without p53 deletion/mutation (3)
- Fludarabine: a purine nucleoside analogue drug
- Cyclophosphamide: DNA alkylating drug
- Rituximab: monoclonal antibody targeting CD20
Combination:
**Fludarabine + Cyclophosphamide + Rituximab (FCR)
**Bendamustine + Rituximab (BR)
What are the standard treatment options for patients with CLL:
For ‘unfit’ patients without p53 deletion/mutation (3)
- Chlorambucil + Rituximab (CR)
2. Bendamustine + Rituximab (BR)
What are the Novel therapies used in CLL treatment? Can be used in p53 deletion/mutation (3)
- Ibrutinib (BTK inhibitor)
- Idelalisib (PI3K inhibitor)
- Venetoclax (BCL2 inhibitor)
What are the limitations and side effects of ibrutinib? (2)
- It is non curative
2. Can cause transcient increase in peripheral blood lymphocytosis.
What is Cell based therapy for CLL? What marker does it target on surface of tumour cell? (2)
Chimeric antigen receptor T cells (CAR T). It targets CD19 on surface of tumour.
