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BMS3031 - Molecular mechanisms of disease - S1 2026
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A melanoma patient with a B-RAF(V600E) tumour initially responds well to the BRAF inhibitor vemurafenib, but the tumour later resumes rapid growth. Genetic analysis reveals the presence of a p61 B-RAF(V600E) splice variant that lacks part of the regulatory region of the protein.
Which mechanism best explains why this variant confers resistance to vemurafenib?
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?
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?
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?
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?
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?
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?
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?
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?
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?