Foundation B Block MCQs

Question 1: Which of the following is a key characteristic of EMT in cancer progression?

A) Upregulation of E-cadherin and downregulation of N-cadherin
B) Decreased production of matrix metalloproteinases (MMPs)
C) Transition from motile mesenchymal cells to stationary epithelial cells
D) Increased expression of N-cadherin and loss of E-cadherin
E) Activation of tumour-suppressor genes

Question 2: What is the role of TGF-β and its receptor (TGF-β RII) in colorectal cancer (CRC)?

A) TGF-β signalling promotes tumour suppression by inhibiting cell proliferation.
B) Loss of TGF-β RII function leads to uncontrolled cell proliferation.
C) SMAD4 mutation enhances TGF-β signalling.
D) TGF-β signalling is irrelevant in colorectal cancer.
E) TGF-β RII activation directly inhibits SMAD proteins.

Question 3: Which of the following best describes the role of p53 in preventing cancer progression?

A) Promotes cell proliferation by activating oncogenes
B) Activates telomerase to prevent cell aging
C) Suppresses the immune system to prevent inflammation
D) Enhances angiogenesis to supply the tumour with blood
E) Initiates DNA repair or apoptosis in response to cellular stress

Question 4: Which of the following mechanisms helps cancer cells evade apoptosis?

A) Activation of proteins like Bax and Bak
B) Downregulation of proteins like Bcl-2
C) Loss of p53 function
D) Increased caspase activation
E) Enhanced expression of death receptors

Question 5: MDM2 primarily regulates p53 by:

A) Enhancing p53’s transcriptional activity
B) Promoting p53 degradation
C) Increasing p53 synthesis
D) Inhibiting p53 phosphorylation
E) Activating p53’s apoptotic function

Question 6: In the presence of Wnt signalling, β-catenin:

A) Accumulates and enters the nucleus
B) Is degraded by the proteasome
C) Remains bound to the destruction complex
D) Inhibits Beta catenin from entering the nucleus
E) Inhibits cell proliferation

Question 7: Which scenario best describes branched evolution in cancer?

A) Sequential mutations produce one dominant clone
B) All cells have identical genetic mutations
C) Multiple sub-clones with distinct mutations arise from a common ancestor
D) Cancer cells evolve linearly without variation
E) Only one type of mutation persists through generations

Question 8: Which of the following best defines a teratoma?

A) A tumour that arises from mesenchymal tissue.
B) A tumour that originates from a single germ cell layer.
C) A malignant tumour composed of only epithelial cells.
D) A benign tumour that only contains adipose tissue.
E) A tumour containing tissues derived from all three germ layers (ectoderm, mesoderm, endoderm).

Question 9: What is desmoplasia in the context of tumours?

A) The growth of abnormal blood vessels within tumours.
B) The presence of necrosis within a tumour.
C) The spread of tumour cells to distant organs.
D) The formation of dense, fibrous tissue around a tumour.
E) The uncontrolled proliferation of epithelial cells.

Question 10: Which of the following best describes the difference between pleomorphism and anaplasia?

A) Pleomorphism refers to variations in size and shape of cells, while anaplasia indicates a lack of differentiation.
B) Pleomorphism describes rapid tumour growth, whereas anaplasia refers to a tumour that has spread.
C) Pleomorphism is a feature of benign tumours, whereas anaplasia is seen only in malignant tumours.
D) Pleomorphism and anaplasia both refer to increased mitotic activity.
E) There is no difference; both terms describe the same cellular feature.

Question 11: What is the significance of the growth fraction in tumours?

A) It represents the number of mutations present in a tumour.
B) It indicates the proportion of tumour cells actively dividing.
C) It measures the size of the tumour’s blood supply.
D) It refers to the metastatic potential of a tumour.
E) It determines the type of tissue from which the tumour originates.

Question 12: Which of the following best describes the primary role of pericytes in angiogenesis?
A) Prevent endothelial cell apoptosis during angiogenesis.
B) Induce the proliferation of immune cells in blood vessels.
C) Stabilise and mature newly formed blood vessels.
D) Increase the permeability of blood vessels.
E) Replace endothelial cells in damaged vessels.

Question 13: Which of the following statements about the tumour microenvironment (TME) is the most accurate in describing its role in tumour progression?

A) The TME primarily supports tumour progression by directly promoting immune cell apoptosis.
B) The TME facilitates metastasis by degrading the extracellular matrix through cancer-associated fibroblasts (CAFs).
C) The TME aids angiogenesis by normalizing vessel formation and stabilizing endothelial cells.
D) The TME promotes immune suppression by recruiting T-regulatory cells and polarizing macrophages to an M2 phenotype.
E) The TME hinders tumour progression by activating CD8+ T cells and natural killer (NK) cells.

Question 14: Which of the following best explains the paradoxical presence of TILs in a tumour despite its immunosuppressive microenvironment?

A) TILs are recruited by chemokines secreted by tumour cells but are rendered ineffective by immune checkpoints like PD-1/PD-L1.
B) TILs lack specificity for tumour neoantigens and, therefore, cannot effectively destroy tumour cells.
C) TILs are entirely comprised of Tregs, which support tumour progression.
D) Tumour cells recruit TILs to promote angiogenesis through VEGF secretion.
E) TILs infiltrate tumours due to inflammation caused by necrotic tumour tissue.

Question 15: Which of the following is NOT a key signal required for full T cell activation?

A) TCR binding to an antigen presented on MHC
B) Co-stimulation via CD28 and CD80/86
C) The secretion of IL-10
D) Cytokine signals, such as IL-2
E) All of the above are required for full T cell activation

Question 16: Which immune checkpoint inhibitor specifically targets PD-1 to enhance T cell function against cancer cells?

A) Ipilimumab
B) Nivolumab
C) Rituximab
D) Trastuzumab
E) Cetuximab

Question 17: The activation of T cells requires which of the following co-stimulatory molecules to bind to CD28?

A) CTLA-4
B) PD-1
C) TGF-β
D) IL-10
E) CD80/CD86

Question 18: Which of the following is the primary role of Myeloid-Derived Suppressor Cells (MDSCs) in cancer?

A) Suppressing T cell activity
B) Enhancing T cell activation
C) Secreting cytokines to stimulate the immune response
D) Engaging tumour cells in direct cytotoxicity
E) Inducing regulatory T cell (Treg) differentiation

Question 19: Which of the following cytokines is primarily secreted by regulatory T cells to suppress immune responses?

A) IL-2
B) IFN-γ
C) TNF-α
D) TGF-β
E) IL-12

Question 20: Which of the following repair pathways is inherently mutagenic?
A) Homologous recombination
B) Non-homologous end-joining (NHEJ)
C) Base excision repair
D) Mismatch repair
E) Nucleotide excision repair

Question 21: Which of the following is a hallmark of transcription-coupled nucleotide excision repair (NER)?
A) Involves global genome repair using XPC
B) Utilises homologous recombination to fix lesions
C) Repairs interstrand crosslinks
D) Primarily repairs oxidative damage
E) Requires Cockayne Syndrome proteins CSA and CSB

Question 22: What is the primary function of the protein PARP1 in the DNA damage response?

A) Detects single-strand breaks and recruits repair machinery
B) Repairs double-strand breaks via homologous recombination
C) Repairs mismatched bases during replication
D) Functions as an exonuclease to degrade damaged DNA
E) Recruits helicases to unwind DNA for transcription

Question 23: Which of the following mechanisms contributes to the carcinogenic potential of H. pylori in gastric cancer?

A) Secretion of exotoxins that directly damage DNA
B) Inhibition of apoptosis in gastric epithelial cells
C) Direct integration of bacterial DNA into the host genome
D) Induction of chronic inflammation and oxidative stress
E) None of the above

Question 24: Which of the following best describes the significance of 8-oxoG in DNA damage and repair?

A) It results from depurination and is repaired by nucleotide excision repair.
B) It forms interstrand crosslinks and is repaired by homologous recombination.
C) It is an oxidative lesion that causes G:C to T:A transversions if unrepaired.
D) It creates bulky adducts repaired by global genome nucleotide excision repair.
E) It inhibits replication by intercalating into the DNA helix.

Question 25: A patient with Cockayne syndrome presents with severe photosensitivity and progressive neurological decline. Which of the following is the primary defect in this condition?

A) Failure to repair bulky DNA adducts in non-transcribed regions of the genome.
B) Defective repair of single-strand breaks during replication.
C) Impaired transcription-coupled nucleotide excision repair.
D) Defective mismatch repair of replication errors.
E) Defective homologous recombination for double-strand break repair.

Question 26: Which of the following mechanisms explains the carcinogenic potential of polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke?

A) Formation of interstrand crosslinks that block replication.
B) Covalent DNA adduct formation repaired by nucleotide excision repair.
C) Oxidation of guanine residues to 8-oxoG.
D) Methylation of cytosine residues leading to epigenetic silencing.
E) Induction of double-strand breaks via ROS.

Question 27: Which of the following is NOT one of the six original hallmarks of cancer as described by Hanahan and Weinberg?

A) Sustaining proliferative signalling
B) Evading growth suppressors
C) Activating invasion and metastasis
D) Inducing angiogenesis
E) Avoiding immune destruction

Question 28: A 62-year-old woman presents with progressive abdominal distension and weight loss over the past 3 months. Imaging reveals a large ovarian mass, and biopsy confirms high-grade serous ovarian carcinoma. Molecular testing identifies a mutation in a tumour suppressor gene that is the most frequently mutated gene across all human cancers. Which of the following is the most likely gene mutation in this patient?

A) BRCA1

B) KRAS

C) TP53

D) PTEN

E) EGFR

Question 29: A 62-year-old patient with a history of smoking presents with a new diagnosis of lung cancer. Molecular testing reveals a mutation in the TP53 gene. Given the role of p53 in regulating the cell cycle and apoptosis, which of the following mechanisms is most likely to occur as a result of the TP53 mutation in this patient’s tumour cells?

A) Increased expression of p21, leading to enhanced inhibition of CDKs and cell cycle arrest at the G1 phase.
B) Impaired activation of caspases, leading to defective apoptosis in response to cellular stress.
C) Enhanced upregulation of FAS receptors, resulting in increased activation of the extrinsic apoptosis pathway.
D) Unregulated phosphorylation of Rb, promoting uncontrolled progression from G1 to S phase.
E) Increased expression of p21, which inhibits CDK2 and prevents the phosphorylation of Rb, leading to sustained G1 arrest.

Question 30: A 45-year-old woman is diagnosed with breast cancer. Molecular testing reveals a mutation in the KRAS gene, which is known to activate proteins involved in signal transduction pathways. This leads to uncontrolled cell proliferation. Which of the following best describes how cancer cells sustain proliferative signalling through the activation of the KRAS pathway?

A) The KRAS mutation leads to the overproduction of growth factors like PDGF, which acts in an autocrine manner to stimulate cell growth.

B) The KRAS mutation results in the upregulation of growth factor receptors such as EGFR, making the cancer cells hypersensitive to external growth signals.

C) The KRAS mutation leads to the activation of downstream signalling proteins, such as RAF and MEK, which continuously promote cell cycle progression without requiring external growth factor signalling.

D) The KRAS mutation allows cancer cells to produce CSF-1, which stimulates macrophages to secrete additional growth factors in a paracrine manner.

E) The KRAS mutation induces the degradation of tumour suppressor genes, which indirectly increases the sensitivity of the cancer cells to growth factors.

Question 31: Which of the following is NOT a mechanism by which cancer cells sustain proliferative signalling?

A) Cancer cells produce their own growth factors in an autocrine manner, such as PDGF in glioblastomas.
B) Cancer cells increase the number of growth factor receptors on their surface, such as upregulating EGFR.
C) Cancer cells activate mutated KRAS proteins that continuously signal for cell cycle progression.
D) Cancer cells downregulate tumour suppressor genes like p21 to enhance growth factor sensitivity.
E) Cancer cells induce the secretion of growth factors by surrounding cells, such as CSF-1 produced by mammary cells to recruit macrophages.

Question 32: Cancer cells often evade apoptosis by manipulating key pathways. Which of the following statements about mechanisms of apoptosis resistance in cancer cells is INCORRECT?

A) Mutations in TP53 impair the activation of pro-apoptotic proteins such as Bax, Bak & Puma, preventing intrinsic pathway apoptosis.
B) Cancer cells can increase the expression of Bcl-2, which inhibits mitochondrial outer membrane permeabilisation.
C) Cancer cells can produce non-signalling decoy FAS receptors to disrupt the extrinsic apoptotic pathway.
D) Production of insulin-like growth factors (IGF) enhances survival signalling, helping cancer cells resist cell death.
E) Decreased expression of anti-apoptotic factors such as Bcl-2 & Bcl-XL is a key mechanism cancer cells use to evade apoptosis.

Question 33: Which of the following statements about enabling replicative immortality and inducing angiogenesis in cancer is INCORRECT?

A) Cancer cells evade the Hayflick limit by upregulating telomerase, which maintains the length of telomeres.
B) Telomerase is functionally absent in most healthy adult cells but is highly active in cancer cells to enable continuous cell division.
C) The angiogenic switch in cancer is often activated by hypoxia, leading to the upregulation of VEGF-A.
D) Cancer cells can only survive when located more than 500μm away from a blood vessel by activating alternative energy pathways.
E) Downregulation of anti-angiogenic factors like TSP-1 (thrombospondin-1) contributes to the vascularisation of tumours.

Question 34: Which of the following mechanisms is central to the ability of cancer cells to metastasise from the primary tumour to distant sites?

A) Overexpression of E-cadherin, promoting increased adhesion and collective migration of cancer cells through the bloodstream.
B) Induction of epithelial-mesenchymal transition (EMT), which reduces epithelial characteristics and enhances migratory and invasive capabilities.
C) Increased synthesis of laminin in the extracellular matrix (ECM), preventing degradation of surrounding tissue and stabilising tumour boundaries.
D) Suppression of N-cadherin, limiting interactions with stromal cells and reducing the ability of cancer cells to colonise distant tissues.
E) Enhanced stabilisation of cell polarity and cytoskeletal organisation, allowing cancer cells to circulate in the bloodstream without detaching from each other.

Question 35: A 58-year-old patient with metastatic colorectal cancer is treated with Cetuximab, an EGFR inhibitor. However, the treatment shows no significant effect. Genetic testing reveals a mutation in the K-Ras gene, specifically the K-RasG12V mutation. Which of the following best explains the lack of response to Cetuximab in this patient?

A) The K-RasG12V mutation causes EGFR to become permanently active, bypassing the need for growth factor binding.
B) The K-RasG12V mutation causes EGFR receptor downregulation, preventing binding of Cetuximab.
C) The K-RasG12V mutation leads to a deficiency in the binding of GTP to K-Ras, rendering the protein inactive.
D) The K-RasG12V mutation allows K-Ras to remain permanently activated, regardless of EGFR signalling, bypassing the effects of Cetuximab.
E) The K-RasG12V mutation reduces the binding affinity of Cetuximab, leading to inadequate inhibition of EGFR.

Question 36: Which of the following best explains how c-myc gene amplification or translocation contributes to cancer development?

A) Amplification of c-myc on chromosome 4 results in excessive production of the c-myc protein, driving uncontrolled cell proliferation.
B) c-myc translocation from chromosome 8 to chromosome 14 reduces its expression by placing it next to the IgH gene, inhibiting tumorigenesis.
C) c-myc amplification is restricted to adult cancers and has no significant role in childhood neuroblastoma prognosis.
D) The HER2/Neu gene amplification, seen in breast cancer, results in the production of c-myc proteins, which are responsible for breast cancer metastasis.
E) c-myc amplification causes a reduction in the production of the c-myc protein, leading to the activation of pro-apoptotic pathways.

Question 37: Which of the following best describes the mechanism by which the Philadelphia chromosome contributes to the development of certain cancers?

A) The translocation of ABL-1 to chromosome 22 next to BCR results in the formation of a hybrid BCR-ABL protein that encodes for a tyrosine kinase with enhanced activity, promoting uncontrolled cell division.
B) The Philadelphia chromosome results in the downregulation of BCR and ABL-1 genes, reducing tyrosine kinase activity and leading to increased apoptosis in affected cells.
C) The BCR-ABL translocation prevents the formation of tyrosine kinases, thereby inhibiting the growth and proliferation of cancer cells.
D) Imatinib targets the BCR-ABL hybrid protein by enhancing its activity, leading to increased signal transduction and cellular proliferation.
E) The Philadelphia chromosome occurs exclusively in Acute Lymphoblastic Leukaemia (ALL) and has no role in other forms of leukaemia, such as Chronic Myeloid Leukaemia (CML).

Question 38: Which of the following best explains how viral genome insertion can contribute to cancer development?

A) Viral genome insertion leads to the random inhibition of tumour suppressor genes, promoting cell cycle progression and tumour formation.
B) If the viral genome inserts next to a gene such as c-myc, it can result in the amplification of that gene, leading to overproduction of the c-myc protein and promoting uncontrolled cell proliferation.
C) Viral genome insertion causes the direct transformation of the host genome into a cancerous form by inducing mutations in tumour suppressor genes.
D) Viral insertion leads to the activation of proto-oncogenes, thereby increasing the risk of uncontrolled cell growth and cancer formation.
E) The viral genome replicates independently of the host genome, without affecting the host’s cellular processes.

Question 39: Which of the following best explains why amplification of the c-myc gene is oncogenic?

A) Amplification of c-myc causes the overproduction of MAD, which binds to MAX and prevents its activation, thereby inhibiting cell proliferation.
B) c-myc amplification results in the continuous expression of MYC, which binds to MAX and activates numerous proliferative signalling pathways, since MAD can no longer bind & inhibit c-myc.
C) The amplification of c-myc leads to the production of a truncated form of MYC that disrupts the MAX binding, thereby inhibiting cell growth and preventing cancer.
D) c-myc amplification results in the loss of MAX expression, leading to the inability to form the MYC-MAX complex, which in turn suppresses cell proliferation.
E) c-myc amplification triggers the activation of tumour suppressor pathways, which downregulate the MYC-MAX complex and prevent cancerous growth.

Question 40: A 3-year-old child presents with unilateral retinoblastoma. Genetic testing reveals that one allele of the RB1 gene is mutated, and the other allele appears to be normal. Based on Knudson’s Two-Hit Hypothesis, which of the following is most likely to occur in this child to develop retinoblastoma?

A) A single mutation in the RB1 gene is sufficient to cause retinoblastoma, and no further genetic alterations are required.
B) The child inherited a mutation in one RB1 allele, and a second, sporadic mutation occurred in the other allele in the affected eye, leading to tumour development.
C) Both alleles of the RB1 gene were mutated at birth, leading to the development of bilateral retinoblastoma.
D) A somatic mutation in the unaffected eye occurred later, resulting in loss of heterozygosity and the development of bilateral retinoblastoma.
E) A mutation in the RB1 gene occurred in both alleles in the unaffected eye during mitosis, leading to retinoblastoma in both eyes.

Question 41: A 5-year-old child with a family history of multiple cancers is diagnosed with a rare tumour. Genetic testing reveals a germline mutation in the p53 tumour suppressor gene. This child is diagnosed with Li-Fraumeni Syndrome. Based on this condition, which of the following is true regarding the cancer risk associated with Li-Fraumeni Syndrome?

A) The child has a 30% likelihood of developing invasive cancer by 30 years old, similar to the general population.
B) The likelihood of developing invasive cancer by 30 years old is 50%, and 90% by 70 years old.
C) The mutation in the p53 gene is always inherited, and it never occurs as a somatic mutation during embryogenesis.
D) Li-Fraumeni Syndrome is inherited in a recessive manner, requiring two mutations in the p53 gene for cancer development.
E) Children with Li-Fraumeni Syndrome typically develop only one type of cancer during their lifetime.

Question 42: A 60-year-old patient presents with a history of colorectal cancer (CRC). Genetic testing reveals mutations in the APC, TGF-β receptor II, and p53 genes. Based on the Vogelgram progression model of CRC, which of the following best describes the role of the APC mutation in the early stages of colorectal carcinogenesis?

A) The APC mutation causes excessive degradation of beta-catenin, leading to increased cellular proliferation in the colon.
B) APC mutations prevent Wnt ligand from binding to stem cells, leading to reduced cellular proliferation and early tumorigenesis.
C) APC mutations lead to persistent activation of beta-catenin, promoting uncontrolled cellular proliferation in the colon crypts.
D) The APC mutation inactivates TGF-β signalling, directly preventing apoptosis and promoting tumour progression.
E) APC mutations inactivate p53 signalling, allowing cells to bypass cell cycle checkpoints and avoid apoptosis.

Question 43: A 55-year-old patient with colorectal cancer (CRC) is diagnosed with a mutation in the TGF-β receptor II gene. Based on the normal signalling mechanism of TGF-β in colorectal epithelial cells, what is the most likely consequence of this mutation in relation to tumour progression?

A) The mutation results in persistent activation of the Smad2/Smad4 complex, leading to excessive cell division and stimulation of tumour growth.
B) The mutation disrupts the recruitment of the Type I TGF-β receptor, impairing the activation of Smad2 and preventing the apoptosis-inducing effects of TGF-β signalling.
C) The mutation leads to enhanced TGF-β secretion, decreasing immune responses that activate tumorigenesis.
D) The mutation causes an abnormal accumulation of the Type I TGF-β receptor, resulting in the sustained activation of pro-apoptotic genes and reduction in tumour proliferation.
E) The mutation prevents the phosphorylation of Smad2, thereby inhibiting the formation of the Smad2/Smad4 complex, which disrupts normal cell-cycle regulation and promotes tumour cell survival.

Question 44: A 45-year-old patient with a family history of colorectal cancer presents with multiple adenomatous polyps in the colon. Genetic testing reveals a mutation in the APC gene. Which of the following is the most likely diagnosis based on this genetic finding?

A) Familial Adenomatous Polyposis (FAP)
B) Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
C) Sporadic colorectal cancer due to environmental factors
D) Colorectal cancer associated with Lynch syndrome
E) Gardner’s Syndrome

Question 45: Which of the following modifications most likely results in the repression of gene transcription by altering the accessibility of the DNA in the chromatin structure?

A) Methylation of CpG islands in the promoter region, preventing transcription factor binding
B) Acetylation of histone proteins, resulting in tight wrapping of DNA around histones
C) Phosphorylation of histone H3 at serine 10, leading to increased chromatin condensation
D) Methylation of histone H3 at lysine 9, promoting euchromatin formation
E) Ubiquitination of histone H2A, enhancing gene transcription

Question 46: Which of the following drugs targets the epigenome by inhibiting DNA methyltransferase activity to modify gene expression in cancer cells?

A) Vorinostat
B) Depsipeptide
C) Dacogen
D) Vidaza
E) Dacogen & Vidaza

Question 47: Which of the following tumour immune microenvironment features is most associated with a poor prognosis in solid tumours due to immune evasion?

A) High CD8+ T-cell infiltration
B) High CD4+ T-cell infiltration
C) High Tumour-Associated Macrophage (TAM) infiltration
D) High Natural Killer (NK) cell activity
E) Low T-Regulatory (T-Reg) cell presence

Question 48: Which of the following statements about Cancer Associated Fibroblasts (CAFs) is true regarding their role in tumour progression?

A) CAFs primarily promote tumour suppression through enhanced immune cell recruitment.
B) CAFs recruit stromal cells from the surrounding tissue to form the tumour stroma, which can increase interstitial pressures and limit drug perfusion.
C) CAFs enhance drug efficacy by degrading metabolic inhibitors in the tumour microenvironment.
D) CAFs are only involved in early tumour development and do not contribute to tumour progression or metastasis.
E) CAFs serve as an indicator of good prognosis due to their role in regulating tissue remodelling.

Question 49: Which of the following statements about Cancer Associated Fibroblasts (CAFs) is incorrect regarding their role in tumour progression?

A) CAFs contribute to tumour progression by recruiting stromal cells to form the tumour stroma, which can increase interstitial pressure and hinder drug delivery.
B) CAFs can degrade certain drugs due to their high concentration of metabolic enzymes like CYP3A4, potentially reducing the efficacy of treatment.
C) CAFs generally only tend to be involved in early stages of tumour development, before metastasis occurs contributing to tumour progression.
D) CAFs can interact with immune cells and inhibit the activation of cytotoxic T cells, helping the tumour evade immune surveillance.
E) CAFs serve as an important prognostic indicator, with higher stromal invasion being associated with poor prognosis due to their role in fibrosis and reduced drug access.

Question 50: Which of the following mechanisms is least likely to contribute to immune evasion in the tumour microenvironment (TME)?

A) Tumours recruit immunosuppressive cells like Tregs, myeloid-derived suppressor cells (MDSCs), and alternatively activated macrophages (AAMs) to suppress the activity of CD8+ T-cells.
B) Tumours lose the ability to present antigens by mutating MHC Class I processing pathways, such as the Tapasin complex, preventing proper presentation to CD8+ T-cells.
C) Tumours inhibit T-cell extravasation by releasing endothelin and secreting factors that increase fibrosis, thereby blocking T-cell infiltration.
D) Tumours induce immune tolerance by engaging immune checkpoint proteins like PD-1/PD-L1 to induce T-cell exhaustion and inhibit T-cell activation.
E) Tumours enhance T-cell-mediated immunity by upregulating the expression of co-stimulatory molecules, such as CD28, on CD8+ T-cells, promoting their activation.

Question 51: Which of the following bacteria is particularly important in the development of mucous-associated colorectal cancer (CRC) due to its ability to adhere to and invade epithelial cells, produce genotoxins like colibactin, and stimulate pro-inflammatory and pro-angiogenic responses?

A) Streptococcus gallolyticus
B) Bacteroides fragilis
C) Enterococcus faecalis
D) E. coli
E) Lactobacillus acidophilus

Question 52: Which of the following mechanisms most accurately describes the role of dysbiosis and bacterial-epithelial interactions in the development of colorectal cancer (CRC)?

A) Dysbiosis shifts the microbiota composition to include higher amounts of Firmicutes and lower amounts of Proteobacteria, which decreases immune system activation and limits DNA damage, thus preventing cancer progression.
B) The reduction of Bacteroides and Firmicutes, along with an increase in Proteobacteria such as E. coli, promotes inflammation by stimulating Toll-like receptors (TLRs), leading to higher cellular proliferation and an increased risk of dysplasia and cancer.
C) Pro-inflammatory cytokines released from bacteria cause the immune system to suppress tumour growth, thereby reducing the incidence of colorectal cancer.
D) Genotoxins produced by bacteria such as E. coli act as pro-carcinogenic agents, but these agents are not able to affect epithelial cell DNA directly due to the protection offered by thicker mucosal layers.
E) The increased presence of polyps due to bacterial overgrowth leads to a thickened mucosa, which acts as a barrier against bacterial adhesion and prevents the progression to colorectal cancer.

Question 53: A 45-year-old patient presents with chronic gastritis and a history of dyspepsia. After undergoing diagnostic testing, it is revealed that the patient is infected with Helicobacter pylori (H. pylori). Which of the following is considered the most important virulence factor of H. pylori that contributes to its increased risk of gastric cancer?

A) OipA adhesion, which facilitates the initial binding to the gastric epithelium.
B) VacA cytotoxin, which is present in all strains of H. pylori and causes cellular damage.
C) CagA cytotoxin, which is injected into epithelial cells and influences signalling pathways linked to cancer progression.
D) BabA adhesion, which enhances H. pylori colonisation by binding to host cell surface carbohydrates.
E) SabA adhesion, which contributes to the persistent colonisation of the gastric epithelium but does not directly increase cancer risk.

Question 54: A 40-year-old patient presents with a diagnosis of squamous cell carcinoma of the head and neck (SCCHN). Testing reveals the presence of Human papillomavirus (HPV) infection in the tumour cells. Based on the molecular pathogenesis of HPV-related cancers, which of the following statements best describes the underlying mechanism of carcinogenesis in this patient?

A) The tumorigenic effect of HPV in SCCHN is primarily due to mutations in the p53 gene, which disrupts the normal regulation of the cell cycle.
B) HPV-related SCCHN is characterised by the inactivation of p53 by the viral E6 protein, which binds to p53 and tags it for degradation, allowing unchecked cell proliferation.
C) HPV infection leads to mutations in the CDKN2A gene, which in turn disables the cell’s ability to progress through the G1 phase, thus inhibiting carcinogenesis.
D) HPV infection results in the overexpression of E2Fs, which bind to Rb and stimulating the progression of the cell cycle into S-phase, thus increasing cell proliferation.
E) The presence of the viral E6 and E7 proteins in HPV-positive SCCHN patients is associated with a worse prognosis and earlier onset of disease compared to HPV-negative SCCHN.

Question 55: A 35-year-old woman with a known BRCA1 mutation presents with an ovarian cancer diagnosis. She is recommended for treatment with a PARP inhibitor. Which of the following mechanisms best explains why PARP inhibitors are effective in treating cancer cells with a BRCA1 mutation?

A) Cancer cells with a BRCA1 mutation rely on non-homologous end joining (NHEJ) for DNA repair, which is enhanced by PARP inhibitors.
B) PARP inhibitors are toxic to healthy cells because they prevent homologous recombination (HR) by inhibiting BRCA1 activity.
C) Cancer cells with a BRCA1 mutation cannot repair DNA via homologous recombination, so PARP inhibitors prevent the backup DNA repair mechanism, leading to synthetic lethality.
D) PARP inhibitors block the function of DNA ligases, preventing the final joining of DNA strands during NHEJ, which is critical for the repair of cancer cells.
E) PARP inhibitors increase DNA repair in cancer cells by activating the homologous recombination pathway, compensating for the defective BRCA1 function.

Question 56: A 60-year-old patient with metastatic melanoma undergoes immunotherapy. Despite some initial response, the tumour begins to progress. Genetic analysis reveals the loss of MHC Class I expression in the tumour cells. Based on the mechanisms of immune evasion described, which of the following most likely explains the tumour’s ability to escape immune surveillance?

A) The tumour has successfully recruited a high number of CD8+ T-cells, which should have killed the cancer cells, but the T-cells are now inactivated by CTLA-4 signalling from Tregs.
B) The tumour has impaired antigen presentation due to the loss of MHC Class I expression, preventing the recognition of tumour-specific antigens by CD8+ T-cells.
C) The tumour cells have upregulated PD-1 receptors on their surface, which bind to PD-1 ligands on CD8+ T-cells, preventing their activation and subsequent tumour killing.
D) The tumour recruits MDSCs to inhibit T-cell infiltration, but this mechanism is less effective in the context of immunotherapy.
E) The tumour induces a fibrotic extracellular matrix (ECM) to prevent T-cell infiltration, and the ECM has been shown to have no effect on the outcome of immunotherapy.