Precision Oncology

Question 1

What type of mutations in mainly involved in acquired drug resistance?

Answer 1

Ancillary mutations

Question 2

Name a third generation EGFR tyrosine kinase inhibitor that targets the T790 mutation.

Answer 2

Osimertinib

Question 3

Name the first selective and reversible EGFR TKI developed to interrupt EGF associated signalling

Answer 3

Gefitinib (used in combination with chemotherapy for the treatment of patients with advanced-stage NSCLC clinical trials)

Question 4

Name the primary resistance mutation in tumours involved with EGFR signalling.

Answer 4

T790M resistance mutation

Question 5

In the AURA trial (osimertinib) which patients did they include and how?

Answer 5

Study included patients with both T790M-positive and negative disease
Recruited patients with advanced NSCLC who had an EGFR-TKI sensitising mutation or who had prior clinical benefit from treatment with an EGFR-TKI

Question 6

IL-6 cytokine activates which transcription factor?

Answer 6

STAT3

Question 7

What is the protein calprotectin involved in?

Answer 7

its a protein complex involved in proliferation and resistance pathways

Question 8

What is the advantages of patient-derived organoids (PDOs)?

Answer 8

Organoids can be genetically modified to elucidate roles of specific mutations in tumourogenesis

Question 9

Where are stem cell-derived organoids derived from?

Answer 9

From both healthy and tumour tissue

Question 10

What are the advantages of a liquid biopsy?

Answer 10

Close monitoring of disease - molecular testing can also serve after the start of the treatment to evaluate the occurrence of resistance mutation. Analysis of circulating tumour cell cDNA in plasma also represents a valuable advance as it provides a non-invasive method for monitoring the diseases burden.

Question 11

Describe a basket trial.

Answer 11

Refers to designs in which a targeted therapy is evaluated on multiple diseases that have common molecular alternations (genome sequencing). Evaluate effectiveness based on underlying mode of action rather than specific form of cancer.

Question 12

Describe an umbrella trial.

Answer 12

Evaluate multiple targeted therapies for a single diseases that is stratified into subgroups by molecular alternation (e.g., therapy targeting the driver mutation in their tumour)

Question 13

Give an example of a basket trial.

Answer 13

CREATE trial - crizotinib

Question 14

Give an example of an umbrella trial.

Answer 14

ALCHEMIST trial - variety of therapies targeting EGFR in NSCLC.