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Loss of the

regulatory region causes constitutive RAS activation, which bypasses BRAF

inhibition and activates MEK

The truncated p61 BRAF

variant enhances binding to MEK, allowing MEK to remain phosphorylated even

when BRAF catalytic activity is inhibited

The splice variant

increases BRAF protein stability, resulting in higher cellular levels that

overwhelm the inhibitor

After exposing cells to UV radiation,

a researcher sequences several regions of DNA and notices that mutations

frequently occur at sites where two pyrimidine bases occur next to each other

on the same DNA strand. These sites correspond to where cyclobutane pyrimidine

dimers are most likely to form.

Which of the following sequences would

therefore be most vulnerable to UV-induced DNA damage?

CATCAT

ATGGTA

TATATA

CACCAG

During a skin examination, a

dermatologist explains that dysplastic nevi are monitored carefully because

they can sometimes represent early stages of melanoma development.

Why are individuals with many dysplastic nevi

considered at higher risk of melanoma?

Dysplastic nevi cause

neighbouring keratinocytes to secrete growth factors that permanently stimulate

melanocyte division

Some

dysplastic nevi contain melanocytes with early oncogenic mutations that can

accumulate additional changes and progress to melanoma

Dysplastic nevi

prevent DNA repair pathways from functioning in surrounding skin cells

Dysplastic nevi

increase UV absorption in the skin, which directly converts normal melanocytes

into melanoma cells

Researchers are investigating

malignant cells that proliferate independently of normal growth constraints.

Detailed molecular profiling identifies multiple alterations affecting

signalling pathways and gene regulation.

Which modification most directly promotes

sustained pro-proliferative signalling in these cancer cells?

Increased

expression of cell surface growth factor receptors driven by gene copy number

gain or enhanced transcription

Strengthening of

intercellular adhesion through elevated cadherin expression, reinforcing growth

inhibition

Loss of telomere

maintenance capacity, resulting in early replicative arrest

Global enhancement of

transcriptional machinery without selective activation of growth

‑promoting pathways

A researcher is studying a solid

tumour in a preclinical model. Genetic or pharmacologic interventions have

blocked angiogenesis, preventing the tumour from forming new blood vessels. The

tumour remains viable but shows changes in its growth and behaviour compared to

untreated controls.

Which aspect of tumourigenesis is most

directly limited by the absence of angiogenesis?

Immune cell

infiltration into the tumour

Recruitment of

cancer-associated fibroblasts to the tumour microenvironment

Migration and

invasion into of the tumour into surrounding tissues

Tumour

growth beyond ~2 mm in diameter, due to insufficient nutrient and oxygen

delivery

A researcher observes a population of

cells in a tissue sample showing abnormal cell division and clonal expansion.

However, there is no evidence of epigenetic alteration or genomic instability.

Which explanation best accounts for

the observed clonal expansion?

Acquisition of

invasive traits has allowed the cells to outcompete surrounding tissue

Early

genetic changes have triggered sustained growth signalling without additional

heritable alterations

Accumulation of

widespread genomic instability has enabled rapid evolutionary diversification

Epigenetic

reprogramming has irreversibly altered cell identity

A patient with metastatic melanoma is

treated with an antibody which blocks the immune checkpoint inhibitor PD-1.

Post-treatment blood analysis shows that cytotoxic T cells exhibit increased

metabolic activity, proliferation, and effector function. Molecular assays

indicate that intracellular PI3K/mTOR and RAS/MAPK pathways in these T cells

are activated.

Which explanation best accounts for

the enhanced anti-tumor immune response?

PD-1 antibodies increase

regulatory T cell suppression in the tumour microenvironment, enhancing effector

T cell activity

PD-1 antibodies decrease

T cell receptor specificity for antigen, indirectly enhancing downstream

PI3K/mTOR and MAPK signalling

PD-1

blockade reduces inhibitory signalling in T cells, allowing activation of

PI3K/mTOR and RAS/MAPK pathways, restoring cytotoxic function

PD-1 antibodies

inhibit oncogenic RAS/MAPK signalling in tumour cells, slowing tumour growth

A new monoclonal antibody directed to

a tumour antigen is tested against a panel of tumour cells in the presence or

absence of innate immune cells. Tumour cell death occurs only when innate

immune cells expressing Fc gamma receptor III (CD16) are present. In contrast,

chemical inhibition of the complement cascade has no effect on tumour killing.

Which mechanism most likely explains

how this antibody mediates tumour cell death?

Antibody triggers

complement activation, leading to lysis of tumour cells

Antibody-bound

tumour cells engage Fc gamma receptors on innate immune cells, inducing

targeted cytotoxicity

Antibody activates

death receptors on tumour cells independently of immune cells

Antibody blocks

tumour cell growth factor signalling, indirectly causing apoptosis

In a lab model of HER2-positive breast

cancer, cells are treated with trastuzumab. Initially, most cells are killed,

but a subset survives and continues proliferating. Sequencing and protein analysis

reveal that the HER2 receptor lacks the extracellular domain required for

trastuzumab binding, though downstream signalling remains active.

Which explanation best accounts for

this resistance?

Cells overexpress

efflux pumps that remove trastuzumab from the extracellular environment

Truncation

of the HER2 extracellular domain prevents trastuzumab binding, allowing

continuous signalling

Antibody-dependent

cell-mediated cytotoxicity kills immune cells instead of tumour cells

Loss-of-function PI3K

mutations reduce signalling, protecting cells from antibody effects

A patient with an aggressive lymphoma

is prescribed a combination of two chemotherapeutic agents. Laboratory studies

show that some cancer cells are resistant to the first drug, while others are

sensitive. The combination therapy results in a much higher overall rate of

cancer cell death compared to either drug alone.

Which explanation best accounts for

the rationale behind using combination chemotherapy in this context?

a cancer cell is insensitive to one agent, it can still be targeted and killed

by the second agent

Using two drugs

allows lower doses of each, reducing side effects

The two drugs are

designed to activate two separate phases of the cell cycle

One drug primes the

cancer cell for apoptosis, and the second drug triggers cell death