Lung cancer vignette

Question 1

1. Demonstrate the application of molecular biology into the clinic using lung cancer as an example:
2. How to implement molecular targeted therapies in the treatment of (lung) cancer.
3. How to select patients in order to give the right treatment to the right patient (“Personalized medicine” or “Precision medicine”).
4. What is the status of lung cancer screening?

Answer 1

x

Question 2

Outcome based on natural course of disease without any intervention

Answer 2

Prognostic biomarkers

Question 3

Outcome based on a specific therapy

Answer 3

Predictive biomarkers

Question 4

Next Gen sequencing has a much higher _____ than old-school Sanger sequencing for detecting mutations.

Answer 4

sensitivity; .01 for NG vs 25% for sanger

Question 5

Sensitivity:

Answer 5

If a person has a disease, how often will the test be positive (true positive rate)?

Put another way, if the test is highly sensitive and the test result is negative you can be nearly certain that they don’t have disease.

A Sensitive test helps rule out disease (when the result is negative). Sensitivity rule out or “Snout”

Sensitivity= true positives/(true positive + false negative)

Question 6

Specificity:

Answer 6

If a person does not have the disease how often will the test be negative (true negative rate)?

In other terms, if the test result for a highly specific test is positive you can be nearly certain that they actually have the disease.

A very specific test rules in disease with a high degree of confidence Specificity rule in or “Spin”.

Specificity=true negatives/(true negative + false positives)

Question 7

Small cell lung cancer (SCLC) accounts for 15% of all lung cancer. 5 year survival is 6% vs 16% for other lung cancers. Are there targeted treatment options available for these patients?

Answer 7

No.

Question 8

3 FDA approved kinase inhibitors for EGFR positive tumors.

Answer 8

Erlotinib, Gefitinib, Afatinib

Question 9

2 FDA approved inhibitors for Anaplastic Lymphoma Kinase (ALK)

Answer 9

Crizotinib, Ceritinib

Question 10

Monoclonal antibodies target EGFR _____, whereas tyrosine kinase inhibitors target EGFR ____. Are any monoclonal antibodies approved for EGFR?

Answer 10

extracellularly; intracellularly

[NO, CETUXIMAB, NECITUMUMAB in trials]

Question 11

Four methods of testing for ALK gene rearrangement?

Answer 11

• Fluorescentin-situhybridization(FISH)
  – Immunohistochemistry(IHC)
  – Reversetranscriptasepolymerasechainreaction(RT- PCR)
  – DNA sequencing

Question 12

Biotech companies have focused on the PD1 receptor as an anti cancer therapy. This is designed to do what?

Answer 12

PD1 - Programmed death receptor. Expressed on T cells. Appears that therapy is designed to prevent recognition of the tumor as “self” allowing an immune response against the tumor. Example of immunotherapy.

Question 13

What is the problem with low-dose spiral CT? The benefit?

Answer 13

95% false + rate. Decreased mortality in 30-pack year smokers by 20%.