Precision medicine & Drug Repurposing

Question 1

How does personalized medicine, individualized medicine or precision medicine (all same shit) work?

Answer 1

Step 1: molecular profiling of each patient
Step 2: use prognostic marker, markers predictive of drug sensitivity/resistance and markers predictive of adverse events
Step 3: assign personalized therapy for each patient

Question 2

What was the old paradigm of treatment? What was the 3 different outcomes of treated patients?
What is the new paradigm? What is the outcome of treated patients?

Answer 2

Old paradigm: one-size-fit-all medicine
=> patients with adverse events
=> patients with no benefits
=> patients with benefits

New paradigm: precision medicine
=> each patient benefits from individualized treatment

Question 3

What are the two options after molecular characterization/profiling (with genomics, transcriptomics, epigenomics or proteomics) of a diseased state after matching a biomarker to a therapy/drug in precision medicine?

Answer 3

1. Matching a new therapy to a disease target/biology

2. Repurposing of known therapies to matching patient population

Question 4

What is important to take into consideration when treating with small molecule inhibitors?

Answer 4

Small molecule inhibitors can only target a precise mutation, it is important to identify the mutations of a patient to give him the right treatment

Question 5

What is the problem with targeted therapies?

Answer 5

Possible to develop resistance over time and tumor starts growing again => disease progression

Question 6

What are the 2 resistance mechanisms linked to targeted therapies?

Answer 6

• Mutations occurring on the target molecule

- Lineage plasticity (cancer occurs from a different pathway modification => alternative pathway)

Question 7

What are the 7 steps for testing drug sensitivity and resistance (in this case for leukemia)?

Answer 7

1. Bone marrow sample (or sample from where the tumor is)
2. Mononuclear cell isolation (or isolation of the tumor cells)
3. Sample viability check
4. Incubation with many oncology drugs (more than 500 drugs)
5. Quality control, curve fitting (dose-response relationship) and drug sensitivity score
6. Leukemia specific drug sensitivity (or other cancer type)
7. Patient-specific drug profile report