Cancer 1 Flashcards
What is role of gate keepers [5] and care taker genes [1]
Gate keepers:
* Directly supresses growth/restricts proliferation
* Cell cycle/cell division regulator genes
* Check point control genes
* Apoptosis - related genes
Care takers:
* Maintains genetic stability: DNA repair proteins
At which stages in cell cycle are checkpoints where cell cycle can be arrested? [2]
G2 / M [1]
G1 / S [1]
Explain how Retinoblastoma occurs (and compare to normal functioning gene) [2]
Unphosphorylated form of Rb: binds to GF E2F - cannot bind the DNA and transcription is blocked
Phosphorylated form of Rb: cannot bind to GF E2F - bind the DNA and transcription goes on uncontrolled growth
Explain how normal proto-oncogenes cause normal cell signalling
- growth factor binds to receptor. two receptors interact (dimerization)
- intracelllar side: phosphorylation of tyrosine
- signalling proteins bind to P-tyrosine
- causes cascade of phosphorylation events
- activates two pathways: MAPK pathway and PI3 Kinase Pathway
- once pathways are activated, activate gene expression and transcription factors occur.
State whether oncogenes and tumour supressor genes are activated by a single or double mutation [2]
Oncogene: single mutation
Tumour supressor genes: double mutation
Explain what happens when p53 becomes mutated [2]
- Mutated p53 does not inhibit cyclin B/ CDK1 complex so cell cycle arrest at G2/M does not occur
- Mutated p53 does not inhibit cyclin E/ CDK2 complex so cell cycle arrest at G1/S does not occur
Explain the role of BRCA1 [1]
Explain the role of BRCA2 [2]
BRCA2:
* Upregulates RAD51
* Causes repair by homologous recombination
BRCA1:
* Broader role upstream of BRCA2, participating in various cellular processes in response to DNA damage.
BRCA1 & BRCA2 are involved in repairing dsDNA crosslinks at which cell cycle check point? [1]
G2/M checkpoint
Which gene increases the amount of telomerase? [1]
What happens if this is upregulated? [1]
Telomerase reverse transcriptase(TERT)
If gene upregulated allows the cancer cell to have unlimited replication
Malignant neuroectodermal tumours are called what? [1]
Glioma/ neuroblastoma
Grading of cancer is based on which two factors? [2]
- Degree of anaplasia (degree of differentiation)
- Rate of growth
Staging of cancer is based on which two factors? [2]
1 Size of tumour
2 Extent of growth (or spread)
Explain TNM staging of tumours [3]
T- size of the cancer and how far it has spread into nearby tissue
* T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T’s may be further divided to provide more detail, such as T3a and T3b.
N refers to whether the cancer has spread to the lymph nodes – it can be between 0 (no lymph nodes containing cancer cells) and 3 (lots of lymph nodes containing cancer cells)
* N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer.
M refers to whether the cancer has metastasised – it can either be 0 (no spread) or 1 (the cancer has spread)
Metastatic breast cancer:
Which genes are downregulated? [2]
Which genes are upregulated? [1]
Downregulated:
* BRCA1
* E-cadherin
Upregulated:
* VEGF
Which cancers do we screen for in the UK? [4]
Retinoblastoma
Bowel-FiT
Cervical
Breast
Name 5 red flags in a patient that would indicate cancer in patients [5]
Weight Loss
Lumps:
* Anywhere
* Throat/mouth/neck
* Primary or secondary
Symptoms of Anaemia and/or Infections
Unexpected Bleeding:
PU, PV, PR, Resp, Bruises
Changes: voice; stamina/SOB; moles; back pain, bone pain, swallowing; bowels; complexion (jaundice/pallor); itching
What are the different types of biopsy? [6]
- Transcutaneous
- Endoscopic Biopsy
- Laparoscopic Biopsy
-
Image-directed (with fine-needle aspiration or
cutting needle)
–Ultrasonography
–Computerized tomography
–Magnetic resonance imaging - Open incisional ( portion of the tumor)
- Open excisional (all tumor mass removed)
What are the 5 types of surgical treatment? [5]
- Local resection
-
Radical resection with en-bloc resection of
lymph nodes - Supra-radical resections = LN+Organs
- Surgery for metastasis/recurrence
- Surgical management of complications
Name a classification type for bowel cancer [1]
Dukes Classification
What are the 3 categories of surgery? [3]
1. Open Surgery
2. Minimally Invasive Surgery (MIS)
Hand Assisted (MIS)
Laparoscopic Surgery
Robot Assisted Surgery
Surgery thru natural orifice (NOTES)
3. Image Guided Surgery
What are the 4 types of minimally invasive surgery? [4]
2. Minimally Invasive Surgery (MIS)
Hand Assisted (MIS)
Laparoscopic Surgery
Robot Assisted Surgery
Surgery thru natural orifice (NOTES)
Which types of urological cancer are now treted robotically? [4]
- Prostate cancer – robotic prostatectomy
-
Bladder cancer – robotic cystectomy with
urinary diversion - Renal cancer – robotic partial nephrectomy
-
Testis cancer - robotic retroperitoneal lymph
node dissection
Name three cancers that often diagnosed late [3]
Ovarian
Pancreatic
Myeloma
Which of the following is targeted by Atezolizumab
PD-1
CTLA-4
PD1-Ligand
LAG-3
PD2-Ligand
Which of the following is targeted by Atezolizumab
PD-1
CTLA-4
PD1-Ligand
LAG-3
PD2-Ligand
Which of the following is an example of a CAR-T drug?
Tisagenlecleucel (Kymriah)
Atezolizumab
Ipililumbab
Nivolumab
Which of the following is an example of a CAR-T drug?
Tisagenlecleucel (Kymriah)
Which of the following binds to CD20 in its mechansim of action?
Tisagenlecleucel (Kymriah)
Atezolizumab
Rituximab
Ipililumbab
Nivolumab
Which of the following binds to CD20 in its mechansim of action?
Rituximab
Which of the following binds to CTLA4?
Tisagenlecleucel (Kymriah)
Atezolizumab
Rituximab
Ipililumbab
Nivolumab
Which of the following binds to CTLA4?
Tisagenlecleucel (Kymriah)
Atezolizumab
Rituximab
Ipililumbab
Nivolumab
Describe what checkpoint inhibition is [1]
State two key molecules influential in checkpoint inhibition [2]
Checkpoint inhibitors: take the brakes off the immune system; checkpoints inhibits the stop sign that a cancer cell usually presents to immune cells
Checkpoints (caused by)
PD1 Programmed Death Receptor 1
CTLA-4 Cytotoxic T-Lymphocyte Associated protein 4
Explain the role of the PD1 checkpoint [2]
PD1 regulates T cell activation through binding with the ligands programmed death-ligand 1 (PDL1) and programmed cell death 1 ligand 2 (PDL2)
Under physiological conditions this inhibits T cell proliferation and survival: helps prevent the immune system from attacking itself
Cancer cells can hijack this pathway to escape immune detection
Explain the influence of cancer cells on PD1 checkpoint
Cancer cell can turn off the PD-1 pathway:
.
If PDL1 or PDL2 are expressed within the tumour microenvironment (TME), the ligands can bind to PD1, terminating TCR signalling and reducing the activation of T cells.
Which drugs bind to PD-L1? [3]
Atezolizumab
Durvalumab
Avelumab
Which drugs bind to PD-1? [2]
Pembrolizumab
Nivolumab
Explain the role of CTLA-4 [1]
What happens if CTLA-4 is inhibited? [1]
CTLA-4 suppressed T cell activation and inhibits cell function; plays a role in T-cell priming
Inhibiting CTLA-4 ”takes the breaks off” the immune system
Name two drugs that inhibit CTLA-4
Ipilimubab
Tremelimubab
What are the three ways that monoclonal antibodies are broadly used? [3]
Complement mediated lysis: unconjugated
Immunotoxins: Coupled to toxin
Radioimmunoconjugates: Coupled to radioisotopes
Give an example that is a chimeric monoclonal antibody used for treating B-Lymphomas [1]
What is the target? [2]
Rituximab: targets CD20 on malignant B-cells and CD3 on normal T cells
Together enhance cytotoxicity
What are Chimeric antigen receptors? [1]
Chimeric antigen receptors (CARs): are recombinant receptors for antigens which redirect the specificity and function of T lymphocytes and/or other immune cells in a single molecule.
(Chimeric antigen receptors: on the surface we have the antibody components so the T cells are recognised by the antigen on the tumour cells, and 2nd and 3rd generation CARs have additional costimulatory molecules to enhance the immune response)
Give an example of CAR-T drug for targetting large B-cell lymphoma? [1]
What is the drug target? [1]
Tisagenlecleucel (Kymriah)
CAR-T Cell targeting CD19
What is the point of using immunotherapy biomarkers? [1]
Name 3 key biomarkers for immunotherapy
All cancer treatment comes with AES. If can ID patients who will likely have least AEs then best cost / benefit: using biomarkers can try and ID.
General immune status (how many T cells are in the tumour)
Absence of checkpoints
Tumour insensitivty to immune effectors
(listen over quickly)
Explain the mechanism of how chimeric antigen receptor treatment occurs [3]
Take T cells
Retrovirally transfect them to be able to express the chimeric antigen whereby you have the antibody on the surface linked into the molecule that activates the T cell
(T cells are removed from a cancer patient and modified so they express receptor specific to the patient’s cancer, then are reintroduced to patient)
T cell then recognises the tumour cell and that activated tumour cell kills off these cells
Which of the following is targeted by Pembrolizumab
PD-1
CTLA-4
PD1-Ligand
LAG-3
PD2-Ligand
PD-1
Which of the following binds uses this as its mechanism of action
Tisagenlecleucel (Kymriah)
Atezolizumab
Rituximab
Ipililumbab
Nivolumab
Which of the following binds to CD19 in its mechansim of action?
Tisagenlecleucel (Kymriah)
Which drug prevents the HER2/HER3 dimer from forming?
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Which drug prevents the HER2/HER3 dimer from forming?
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Herceptin is also known as
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Herceptin is also known as
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Which drug stops HER2 binding to another HER2
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Which drug stops HER2 binding to another HER2
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Tarceva
(Erlotinib) targets which of the following
HER2
HER2/HER3
EGFR
VEGF
Tarceva
(Erlotinib) targets which of the following
HER2
HER2/HER3
EGFR
VEGF
Which drug has a side effect of a rash?
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Which drug has a side effect of a rash?
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Which drug causesa decline in left ventricular function AND congestive heart failure
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Which drug causesa decline in left ventricular function AND congestive heart failure
Trastuzumab
Pertuzumab
Cetuximab
Kadcycla
Which drug blocks ATP binding to tyrosine kinase receptor
Trastuzumab
Pertuzumab
Osimertinib
Erlotinib
Kadcycla
Which drug blocks ATP binding to tyrosine kinase receptor
Trastuzumab
Pertuzumab
Osimertinib
Erlotinib
Kadcycla
Which of the following drug binds to B
Trastuzumab
Pertuzumab
Osimertinib
Erlotinib
Kadcycla
Which of the following drug binds to B
Trastuzumab
Pertuzumab
Osimertinib
Erlotinib
Kadcycla
Which of the following drug binds to C
Trastuzumab
Pertuzumab
Osimertinib
Erlotinib
Kadcycla
Pertuzumab
Which drug acts according to this image as a first line drug used for non-small cell lung cancer
Trastuzumab
Pertuzumab
Osimertinib
Erlotinib
Kadcycla
Which drug acts according to this image as a first line drug used for non-small cell lung cancer
Trastuzumab
Pertuzumab
Osimertinib
Erlotinib
Kadcycla
