week 7: cancer and cancer genomics

Question 1

Why is age a major factor in cancer development?

Answer 1

Because with age, DNA repair mechanisms weaken, allowing more mutations to accumulate, increasing cancer risk.

Question 2

What is metastasis and why is it dangerous?

Answer 2

Metastasis is the spread of cancer to secondary organs (e.g. brain, liver), making it harder to treat and increasing mortality risk.

Question 3

How does cancer develop?

Answer 3

Caused by accumulated mutations over time

Triggered by factors like UV radiation

Requires multiple mutations affecting cell survival and division

May lead to dysplasia and malignant transformation

Question 4

What is the significance of cancer heterogeneity?

Answer 4

Not all cancers are the same

Tumours vary in mutation type, cell population, and response to treatment

Question 5

What is the “banana curve” used for in cancer therapy?

Answer 5

It’s used to track progression-free survival, tumour reduction, and relapse rates in response to treatment.

Question 6

What are differentiating agents and how do they work?

Answer 6

Used in blood cancers

Make immature cancer cells mature into non-cancerous cells

Example: Retinoids

Question 7

How does hormone therapy help treat cancer?

Answer 7

Blocks hormone receptors on cancer cells

Prevents hormone-driven proliferation

Reduces relapse and tumour growth

Question 8

What are anti-emetics used for in cancer therapy?

Answer 8

Prevent nausea and vomiting

Examples: NK1 receptor antagonists, 5HT3 receptor blockers

Question 9

What is loperamide used for in cancer therapy?

Answer 9

To manage diarrhoea, a common side effect of chemotherapy.

Question 10

How does RTK (receptor tyrosine kinase) signalling contribute to cancer?

Answer 10

Overactive RTKs → constant cell proliferation

Due to excess ligands or mutations

Leads to uncontrolled cell division

Question 11

What does an RTK inhibitor like imatinib do?

Answer 11

Blocks the kinase domain of RTKs

Prevents signalling and proliferation

Used in cancers like CML

Not curative but functionally effective

Question 12

What are KRAS inhibitors and who benefits most?
A:

Answer 12

Inhibit mutated KRAS proteins, which are common in smokers

Example: Sotorasib, which binds to cysteine on KRAS-G12C to inhibit its activation

Question 13

How does HPV contribute to cancer?

Answer 13

Human papillomavirus (HPV) causes cervical, anal, and penile cancers

Prevention: Vaccination

Question 14

How are monoclonal antibodies produced?

Answer 14

Inject mouse with antigen

Isolate spleen cells

Fuse with myeloma cells to form hybridomas

Select clones producing desired monoclonal antibodies

Question 15

What is ADCC (Antibody-Dependent Cellular Cytotoxicity)?

Answer 15

NK cells bind to Fc region of antibodies on tumour cells → release perforin and granzymes

Leads to cell death

Example: Rituximab (anti-CD20)

Question 15

What are the two functional uses of IgE antibodies in cancer therapy?

Answer 15

Block surface growth receptors (antagonists)

Trigger immune attack on tumour cells

Question 16

What is ligand blocking in antibody therapy?

Answer 16

Antibody binds to ligand, preventing it from activating its receptor

Example: Bevacizumab (binds VEGF-A → inhibits angiogenesis)

Question 16

What is ADCP (Antibody-Dependent Cellular Phagocytosis)?

Answer 16

Macrophages bind Fc region → engulf and digest tumour cells

Example: Alemtuzumab (targets CD52)

Question 16

What is CDC (Complement-Dependent Cytotoxicity)?

Answer 16

Antibody activates complement system → forms MAC (membrane attack complex)

Causes cell lysis

Example: Ofatumumab

Question 17

What is receptor blocking in antibody therapy?

Answer 17

Antibody binds to tumour cell receptor, preventing activation

Example: Trastuzumab (binds HER2)

Question 18

How does Rituximab work?

Answer 18

Anti-CD20 antibody

Binds B cells in B-cell leukaemia

Causes immune-mediated cell death

Question 19

What is HER2 and how does trastuzumab treat HER2+ cancer?

Answer 19

HER2 is a receptor tyrosine kinase

Trastuzumab inhibits dimerisation and internalises the receptor → prevents signalling

Question 20

What is the mechanism of cetuximab in EGFR+ cancers?

Answer 20

Binds EGFR, blocks ligand binding and receptor dimerisation

Induces apoptosis in tumour cells

Question 21

What is the difference between a driver and a passenger mutation in cancer?

Answer 21

Driver mutations promote cancer development by giving a growth or survival advantage.

Passenger mutations are incidental and do not contribute to cancer progression.

Question 22

What types of somatic mutations can occur in cancer?

Answer 22

Non-coding mutations (e.g., promoter mutations, splicing variants) Coding mutations (e.g., synonymous, missense, truncating, frameshift) Copy number variants (amplifications or deletions) Translocations

Question 23

How can synonymous mutations still affect cancer biology?

Answer 23

Though they do not change amino acids, they can affect mRNA stability, splicing, or translation efficiency.

Question 24

What is meant by cancer evolution?What is meant by cancer evolution?

Answer 24

Cancer evolves through accumulation of somatic mutations under selective pressure from environment, immune system, and therapy, leading to clonal diversity.

Question 25

Why is cancer considered a heterogeneous disease?

Answer 25

Different patients (and even different tumour cells within a patient) have distinct mutational profiles, drug responses, and tumour behaviours.

Question 26

What causes resistance to cancer therapies over time?

Answer 26

Secondary mutations, gene amplifications, and activation of alternative signalling pathways (e.g., EGFR, BRAF, MEK) can enable cancer cells to escape targeted inhibition.

Question 27

How does the BRAF V600E mutation affect melanoma treatment?

Answer 27

This mutation activates the MAPK pathway. Drugs like vemurafenib target BRAF, but resistance often develops via MEK activation, NRAS mutations, or PTEN loss.

Question 28

What is an example of drug resistance in lung cancer treatment?

Answer 28

In EGFR-mutated lung adenocarcinoma, the T790M mutation confers resistance to Gefitinib, an EGFR tyrosine kinase inhibitor.

Question 29

What is the role of biomarkers in cancer therapy?

Answer 29

Biomarkers predict which patients will respond to specific treatments, enabling precision medicine. Example: HER2 amplification → trastuzumab response.

Question 30

Give an example of a predictive biomarker used in clinical oncology.

Answer 30

HER2 amplification → response to trastuzumab (breast cancer) BRAF V600E → response to vemurafenib (melanoma) EML4-ALK fusion → response to crizotinib (NSCLC)

Question 31

What is the OncoBird platform used for?

Answer 31

It is a bioinformatics tool to identify response biomarkers and tumour subtypes in clinical trial data.

Question 31

What are the main phases of the drug discovery pipeline?

Answer 31

Early Drug Discovery: target ID, lead optimisation Preclinical Development: ADME, tox, formulation Clinical Trials: Phases I–III Regulatory Approval

Question 32

What do pharmacokinetics (PK) and pharmacodynamics (PD) describe?

Answer 32

PK: What the body does to the drug (ADME) PD: What the drug does to the body (biological effect)

Question 33

What is the importance of cell line models in cancer research?

Answer 33

They are cost-effective, scalable, and useful for high-throughput drug screening and biomarker discovery.

Question 34

Which drug is effective for HER2+ breast cancer?

Answer 34

Lapatinib or trastuzumab – both target the HER2 receptor (ERBB2)

Question 35

Which drug is effective in EGFR-mutant NSCLC?

Answer 35

Gefitinib – targets EGFR-activating mutations like L858R or Exon 19 deletion

Question 36

What is the mechanism of crizotinib in lung cancer?

Answer 36

Crizotinib targets EML4-ALK fusion proteins in NSCLC, inhibiting ALK signalling.