Lung cancer

Question 1

What percentage of lung cancers are caused by smoking?

Answer 1

71%

Question 2

Why are survival rates of lung cancer so low?

Answer 2

Very few symptoms early on, only present in later stages

Rapid progression

Less funding so fewer advances in treatment options

Social stigma

Tumour resistance

Question 3

What are the two main reasons for tumour resistance in lung cancer?

Answer 3

Intratumour heterogeneity

Lack of biomarkers

Question 4

Which are 3 features we can use to categorize lung cancer?

Answer 4

Histology

Molecular mutations

Staging

Question 5

Which histological features are used to categorize lung cancers?

Answer 5

Small cell/neuroendocrine

Non small cell

Question 6

Which molecular mutations are commonly found to cause lung cancer?

Answer 6

EGFR

ROS

ALK

PD-L1

Question 7

Which 3 features do we look at to stage non small cell cancer?

Answer 7

T - primary cancer

N - regional lymph node

M - distal metastasis

Question 8

What is ECOG?

Answer 8

Scale used to assess a patients fitness to undergo treatment

0-5 scale

0 = fully active
5 = dead

Question 9

What is the importance of mutations in cancer cells?

Answer 9

Trigger signalling pathways which confer survival advantage to cells compared to somatic cells

Question 10

Which signalling pathways confer survival advantages to cancer cells?

Answer 10

Block oncogene pathways

Decrease apoptosis of cancer cells

Increase mutations of cells leading to relapse

Question 11

What are the three main treatments of lung cancer?

Answer 11

Chemotherapy

Radiotherapy

Molecular therapy

Question 12

Which chemotherapy is used in lung cancer?

Answer 12

Dual agent chemotherapy (platinum + another)

Docetaxel monotherapy

Question 13

When do we use Docetaxel instead of dual agent chemotherapy?

Answer 13

Used for patients who do not respond to dual agent chemotherapy and are fit enough

Question 14

What are the 3 types of radiotherapy?

Answer 14

Curative

Adjuvant

Palliative

Question 15

What does molecular therapy target?

Answer 15

Protein mutations

Tyrosine kinase

Immune checkpoints

Question 16

How does molecular therapy target tyrosine kinase?

Answer 16

Via tyrosine kinase inhibitors

Blocks signalling pathways preventing the tyrosine kinase from signalling to the nucleus

Question 17

What is an example of a checkpoint inhibitor?

Answer 17

PD-1 and PD-L1 blockade

Question 18

How does the checkpoint inhibitor Pembrolizumab act?

Answer 18

Blocks either the PD-1 on T-cells or PD-L1 on the tumour cells

Prevents the tumour cell from binding to the T cell and inhibiting it

Therefore the active T cell kills the tumour cells by cytotoxic killing

Question 19

Why are MSCs immune priviledged?

Answer 19

Do not elicit an immune reaction

Question 20

What is the role of MSCs in stromal tissue cells?

Answer 20

Precursors of stromal tissue cells

Question 21

Where are MSCs found in the body?

Answer 21

Bone marrow

Umbilical cords

Question 22

How often do MSCs divide?

Answer 22

They show 5 population doublings per week

Question 23

What important fact was discovered about MSCs?

Answer 23

They home to tumors

Question 24

Why do MSCs home to tumors?

Answer 24

Microenvironment created by tumour cells releasing cytokine and matrix protein

Recognised by the conjugate receptors on MSCs

Question 25

Which cytokines released from tumours are MSCs especially attracted to?

Answer 25

MIF Activates ERK and JNK through CXCR4

Question 26

How was the importance of MIF in homing MSCs to cancer cells discovered?

Answer 26

Study that knocked down the MIF signalling from cancer cells Knockout of MIF lead to no MSCs homing to cancer cells

Question 27

What is the TRAIL pathway?

Answer 27

TNF-related apoptosis inducing ligand Induces the extrinsic pathway of apoptosis by binding to its receptor (TRAI)

Question 28

How are tumour cells related to the TRAIL pathway?

Answer 28

Tumour cells express TRAI So if we can activate its apoptosis by expressing TRAIL we can specifically target cancer cells

Question 29

Which apoptotic pathways do chemotherapy and radiation elicit?

Answer 29

Intrinsic apoptotic pathway More of a destructive mechanism for killing mutated cells

Question 30

Why can't we use TRAIL injections to kill cancer cells?

Answer 30

Very short half-life Leads to cytotoxicity due to continuous dosages needed to provide effective treatment

Question 31

What is used to inject TRAIL into the host organism?

Answer 31

Modify MSCs to express TRAIL ligand and trigger the extrinsic apoptotic pathway

Question 32

What were the steps taken to ensure MSCs modified to express TRAIL were an effective therapy against lung cancer?

Answer 32

Construction of the TRAIL lentivirus Prove that MSCTRAIL was effective at killing cancer cells Prove that MSCTRAIL homed toward the tumour Prove that MSCTRAIL effectively reduced tumour growth

Question 33

How was the TRAIL lentivirus constructed?

Answer 33

Lentivirus conjugated with doxycycline Doxycycline could turn on or off the expression of TRAIL in the MSCs Marked TRAIL with luminescent biomarker to be able to spot MSCs

Question 34

How was it shown that dox effectively turned the production of TRAIL on?

Answer 34

Measured the concentration of TRAIL produced by the lentiviruses Lentiviruses without dox did not produce TRAIL Lentiviruses with dox produced TRAIL

Question 35

What was used to show that MSCs homed towards tumour cells?

Answer 35

DiL labelled MSCs

Question 36

What is TRAIL synergy?

Answer 36

When MSCTRAIL therapy works together with other therapies to heighten their therapeutic effects

Question 37

What are mechanisms of TRAIL synergy?

Answer 37

Radiotherapy increases TRAIL receptors Radiotherapy increases MSC homing Chemotherapy increases TRAIL induced caspase cleavage Chemotherapy downregulates inhibitors of apoptosis

Question 38

What was observed in the homing of MSCTRAIL in the lungs?

Answer 38

DiL-labelled MSCs showed that clusters wedge into the capillaries at first pass (90%) Ideal for treating lung cancer

Question 39

Describe the extrinsic pathway of apoptosis

Answer 39

TRAIL L binds to the trimerised receptor Activates FADD protein that connect the Casp8 to the receptor Activation of FADD leads to activation of Casp8

Question 40

How was it proven that the extrinsic pathway was activated upon binding of MSCs to tumour cells?

Answer 40

Dominant negative construct of FAD was inserted into the tumor cells Cancer cells were no longer apoptosed

Question 41

What is a dominant negative FAD construct?

Answer 41

Protein that no longer connect the Casp8 to the TRAIL receptor

Question 42

Which ECOG patients are eligible for chemo?

Answer 42

0-2 stage

Question 43

How many lung cancer patients survive after 10 years

Answer 43

5%

Question 44

How common is lung cancer death?

Answer 44

most common cancer DEATH - 1/5 cancer deaths

Question 45

Lung cancer prognosis has improved a lot since the 70s TRUE or FALSE

Answer 45

False

Question 46

What are the types of curative radiotherapy?

Answer 46

SABR (stereotactic body radiation therapy) EBRT (external beam radiation therapy) - with Surgery (may take wedge, lobe or lung)