USMLE Step 1 Quiz
Practice Cancer Biology And Neoplasia in USMLE Step 1 with focused quiz questions that help you check what you know, review explanations, and build confidence with test-style prompts.
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A 62-year-old man is found to have a 4-cm mass in his kidney on an abdominal CT scan performed for an unrelated reason. A biopsy confirms clear cell renal cell carcinoma. The pathologist notes that the tumor is highly vascular. This type of tumor is often associated with mutations in the VHL gene.
The prominent neovascularization seen in this patient's tumor is primarily driven by the overexpression of which of the following factors, which is normally degraded in a VHL-dependent manner?
This quiz focuses on Cancer Biology And Neoplasia, giving you a quick way to practice the rules, question types, and explanations that matter most for USMLE Step 1.
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A 62-year-old man is found to have a 4-cm mass in his kidney on an abdominal CT scan performed for an unrelated reason. A biopsy confirms clear cell renal cell carcinoma. The pathologist notes that the tumor is highly vascular. This type of tumor is often associated with mutations in the VHL gene.
The prominent neovascularization seen in this patient's tumor is primarily driven by the overexpression of which of the following factors, which is normally degraded in a VHL-dependent manner?
Explanation: The von Hippel-Lindau (VHL) protein is a tumor suppressor that is part of a ubiquitin ligase complex. Under normoxic conditions, VHL targets hypoxia-inducible factor 1-alpha (HIF-1α) for ubiquitination and proteasomal degradation. When VHL is mutated, HIF-1α is stabilized even in the presence of oxygen. HIF-1α then acts as a transcription factor, upregulating the expression of pro-angiogenic factors like vascular endothelial growth factor (VEGF) and PDGF, leading to intense neovascularization.
A 70-year-old man with a history of small cell lung cancer presents to the emergency department with progressive proximal muscle weakness. He reports difficulty rising from a chair and climbing stairs. On examination, his strength improves with repeated muscle contraction. Deep tendon reflexes are diminished.
This patient's neurologic syndrome is caused by autoantibodies directed against which of the following targets?
Explanation: This patient has Lambert-Eaton myasthenic syndrome (LEMS), a paraneoplastic syndrome most commonly associated with small cell lung cancer. LEMS is caused by autoantibodies that target presynaptic voltage-gated calcium channels at the neuromuscular junction. This impairs the influx of calcium required for acetylcholine release, leading to proximal muscle weakness. The characteristic improvement with repeated contraction (facilitation) is due to the accumulation of intracellular calcium with successive nerve impulses, which overcomes the antibody-mediated blockade.
A research study is investigating the metabolic properties of cancer cells. The researchers culture cervical cancer cells in a medium containing abundant oxygen and glucose. They observe that the cells consume glucose at a high rate and produce large amounts of lactate, despite the presence of sufficient oxygen for aerobic respiration.
This metabolic phenotype, known as the Warburg effect, provides a growth advantage to cancer cells primarily by which of the following mechanisms?
Explanation: The Warburg effect, or aerobic glycolysis, describes the phenomenon where cancer cells preferentially use glycolysis for energy production even in the presence of oxygen. While this is less efficient for ATP production compared to oxidative phosphorylation, it is advantageous for rapidly proliferating cells because it allows glycolytic intermediates (e.g., glucose-6-phosphate, fructose-6-phosphate) to be shunted into anabolic pathways, such as the pentose phosphate pathway for nucleotide synthesis and pathways for amino acid and lipid synthesis. These are the building blocks required for creating new cells.
A 65-year-old man is diagnosed with colon adenocarcinoma. During surgery, multiple nodules are found on the surface of the liver. A biopsy confirms metastatic disease. The surgeon notes that the primary tumor has invaded through the entire bowel wall.
The process of tumor cell invasion through the basement membrane and extracellular matrix to reach the portal circulation was most likely facilitated by the secretion of which of the following?
Explanation: For tumor cells to metastasize, they must first breach the basement membrane and invade the surrounding extracellular matrix (ECM). This is accomplished by secreting proteolytic enzymes. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are crucial for degrading components of the ECM, such as collagen, laminin, and fibronectin. Increased expression and activity of MMPs are hallmarks of invasive cancers.
A 28-year-old woman is evaluated for a family history of cancer. Her father died of a sarcoma at age 35, her paternal aunt had breast cancer at age 32, and her cousin has an adrenal cortical carcinoma. Genetic counseling is recommended, and testing reveals a germline mutation in the TP53 gene.
The protein product of the gene mutated in this family normally functions as a 'guardian of the genome' by inducing cell cycle arrest and which other critical process in response to DNA damage?
Explanation: This family's history is classic for Li-Fraumeni syndrome, an autosomal dominant condition caused by a germline mutation in the TP53 tumor suppressor gene. The p53 protein is a transcription factor that is activated in response to cellular stress, such as DNA damage. Activated p53 can halt the cell cycle (primarily at the G1/S checkpoint) to allow time for DNA repair. If the damage is too severe to be repaired, p53 triggers apoptosis (programmed cell death) by upregulating pro-apoptotic genes like BAX.
A 59-year-old man with a long-standing history of polycythemia vera presents with fatigue, night sweats, and significant splenomegaly. His hemoglobin is 18.5 g/dL and his leukocyte count is elevated. His condition is caused by a mutation in a cytoplasmic tyrosine kinase.
Unlike receptor tyrosine kinases, the mutated protein in this patient's condition requires association with a cytokine receptor to initiate downstream signaling through which of the following pathways?
Explanation: Polycythemia vera is a myeloproliferative neoplasm most commonly caused by a gain-of-function mutation in JAK2, a cytoplasmic (non-receptor) tyrosine kinase. JAK2 associates with hematopoietic cytokine receptors, such as the erythropoietin receptor. The V617F mutation makes JAK2 constitutively active, leading to ligand-independent activation of the STAT (Signal Transducer and Activator of Transcription) pathway. This results in uncontrolled proliferation of hematopoietic precursors, primarily of the erythroid lineage.
A 66-year-old woman is being treated for metastatic colorectal cancer with bevacizumab, a monoclonal antibody. After several cycles of treatment, a repeat CT scan shows a significant reduction in the size of her liver metastases.
The therapeutic effect of this drug is primarily achieved by inhibiting which of the following processes essential for tumor growth and metastasis?
Explanation: Bevacizumab is a monoclonal antibody that targets and neutralizes vascular endothelial growth factor (VEGF). VEGF is the primary signaling molecule that stimulates the formation of new blood vessels, a process called angiogenesis. Solid tumors require angiogenesis to grow beyond a few millimeters in size, as they need a blood supply for oxygen and nutrients. By sequestering VEGF, bevacizumab inhibits angiogenesis, thereby starving the tumor and preventing its growth and metastasis.
A 52-year-old woman presents with episodes of facial flushing, watery diarrhea, and wheezing. Physical examination reveals telangiectasias on her face and upper chest. A 24-hour urine collection shows elevated levels of 5-hydroxyindoleacetic acid (5-HIAA). An abdominal CT scan reveals a tumor in the small intestine with liver metastases.
This patient's symptoms are caused by the secretion of which of the following substances from the neuroendocrine tumor?
Explanation: This patient has carcinoid syndrome, a paraneoplastic syndrome caused by a well-differentiated neuroendocrine (carcinoid) tumor that has metastasized to the liver. The primary tumor, often in the small bowel, secretes serotonin and other vasoactive substances (e.g., bradykinin, histamine) into the portal circulation, where they are metabolized by the liver. When liver metastases are present, these substances are secreted directly into the systemic circulation, bypassing hepatic metabolism and causing the classic symptoms of flushing, diarrhea, and bronchospasm. 5-HIAA is the primary metabolite of serotonin.
A laboratory is studying mechanisms of immune evasion by cancer cells. They co-culture melanoma cells with cytotoxic T lymphocytes (CTLs) specific for a tumor antigen. They observe that a subpopulation of the melanoma cells is not killed by the CTLs. Further analysis shows that these resistant cells have significantly reduced surface expression of HLA-A, HLA-B, and HLA-C molecules.
The decreased expression of these surface molecules allows the tumor cells to evade CTL recognition by impairing which of the following processes?
Explanation: Cytotoxic T lymphocytes (CTLs, CD8+ T cells) recognize and kill target cells by binding to peptide antigens presented by MHC class I molecules. HLA-A, HLA-B, and HLA-C are the human MHC class I molecules. By downregulating the expression of these molecules, cancer cells can prevent their tumor antigens from being presented on the cell surface, thereby becoming 'invisible' to and escaping destruction by antigen-specific CTLs. This is a common mechanism of tumor immune evasion.
A 58-year-old man is incidentally found to have an elevated hemoglobin of 19.2 g/dL and hematocrit of 58% on routine blood work. His erythropoietin (EPO) level is markedly elevated, but his oxygen saturation is normal. A CT scan of the abdomen reveals a large mass in the right kidney.
This patient's secondary polycythemia is an example of a paraneoplastic syndrome caused by ectopic production of a hormone by the renal tumor. Which of the following is the most likely mechanism?
Explanation: This patient has paraneoplastic polycythemia secondary to a renal cell carcinoma (RCC). RCC, along with hepatocellular carcinoma and cerebellar hemangioblastoma, can ectopically produce erythropoietin (EPO). This autonomous, unregulated production of EPO by the tumor cells leads to excessive stimulation of the bone marrow, resulting in an overproduction of red blood cells (polycythemia). This is distinct from polycythemia vera, where EPO levels would be low due to a primary bone marrow disorder.
A 30-year-old man presents with bilateral hearing loss and tinnitus. An MRI of the brain reveals bilateral tumors at the cerebellopontine angles, characteristic of vestibular schwannomas. His father had a similar condition. This patient is diagnosed with neurofibromatosis type 2 (NF2).
The gene mutated in this disorder encodes a protein, merlin, which normally functions as a tumor suppressor by which of the following mechanisms?
Explanation: Neurofibromatosis type 2 is caused by mutations in the NF2 gene, which encodes the protein merlin (also known as schwannomin). Merlin is a tumor suppressor protein that links transmembrane proteins, such as E-cadherin, to the actin cytoskeleton. This connection is crucial for establishing stable cell-cell junctions and mediating contact-dependent inhibition of proliferation. Loss of merlin function disrupts these connections, leading to loss of contact inhibition and uncontrolled cell growth, resulting in the formation of tumors like schwannomas and meningiomas.
A 48-year-old woman is diagnosed with metastatic melanoma. Genetic testing of the tumor reveals a V600E mutation in the BRAF gene. She is started on a targeted therapy that inhibits the protein product of this mutated gene.
The BRAF gene is an example of a proto-oncogene that, when mutated, leads to constitutive activation of which of the following signaling pathways?
Explanation: BRAF is a serine/threonine kinase that is a key component of the MAP kinase signaling pathway. This pathway is typically activated by growth factor binding to a receptor tyrosine kinase, which activates RAS, which in turn activates RAF (of which BRAF is a member). The V600E mutation in BRAF makes the kinase constitutively active, leading to constant downstream signaling through MEK and ERK, which promotes cell proliferation and survival, independent of upstream growth signals.
Researchers are studying the replicative potential of human cancer cells in culture. Unlike normal somatic cells, which undergo senescence after a finite number of divisions (the Hayflick limit), these cancer cells appear to be immortal and can proliferate indefinitely.
The limitless replicative potential of these cancer cells is most commonly maintained by the activity of which enzyme?
Explanation: Normal somatic cells have a finite lifespan due to the progressive shortening of telomeres at the ends of chromosomes with each round of DNA replication. Once telomeres become critically short, cells enter a state of replicative senescence or apoptosis. Most cancer cells achieve immortality by upregulating the expression of telomerase, a reverse transcriptase that adds repetitive nucleotide sequences to the ends of chromosomes, thus maintaining telomere length and allowing the cells to bypass senescence and divide indefinitely.
A 22-year-old man is diagnosed with familial adenomatous polyposis (FAP) during a screening colonoscopy, which reveals hundreds of colonic polyps. He undergoes a prophylactic colectomy. He is counseled that he inherited one mutated allele of the APC gene and that the polyps developed after the second allele was lost in individual colonic epithelial cells.
This 'two-hit' model of carcinogenesis is characteristic of genes that function as which of the following?
Explanation: The 'two-hit' hypothesis, proposed by Alfred Knudson, applies to tumor suppressor genes. In familial cancer syndromes like FAP, an individual inherits one defective (mutated) allele in every cell (the 'first hit'). Cancer develops only after the second, normal allele is lost or mutated in a somatic cell (the 'second hit'), leading to a complete loss of function of the tumor suppressor protein. In contrast, proto-oncogenes are typically activated by a single gain-of-function mutation ('one hit').
A 55-year-old woman with a history of invasive ductal carcinoma of the breast, treated 3 years ago, presents with severe low back pain. An MRI of the spine reveals multiple lytic lesions in the L3 and L4 vertebral bodies, consistent with metastatic disease. A biopsy of one of the lesions confirms metastatic adenocarcinoma.
The ability of this patient's tumor cells to detach from the primary mass and invade surrounding tissues is most directly facilitated by the decreased expression of which of the following?
Explanation: Metastasis involves a series of steps, beginning with the dissociation of cells from the primary tumor. This is a key feature of the epithelial-to-mesenchymal transition (EMT). E-cadherin is a transmembrane protein that forms adherens junctions, mediating homotypic cell-cell adhesion in epithelial tissues. Downregulation or mutational inactivation of E-cadherin is a critical event that reduces intercellular adhesion, allowing cancer cells to detach and become motile.
A 32-year-old woman is diagnosed with an aggressive form of breast cancer. Immunohistochemical staining of the tumor tissue is strongly positive for HER2/neu expression. This finding has significant therapeutic implications.
The protein overexpressed in this patient's tumor functions as which of the following?
Explanation: HER2/neu (also known as ERBB2) is a proto-oncogene that encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. Amplification or overexpression of HER2 leads to constitutive activation of the receptor, resulting in ligand-independent dimerization and autophosphorylation. This activates downstream signaling pathways, such as the PI3K/AKT and MAP kinase pathways, driving cell proliferation and survival. Trastuzumab is a monoclonal antibody that targets the HER2 receptor.
A 1-year-old boy is brought to the clinic for evaluation of a white pupillary reflex (leukocoria) in his left eye. His father had the same condition as a child and had his left eye enucleated. The ophthalmologist diagnoses familial retinoblastoma.
The gene responsible for this condition encodes a protein that acts as a negative regulator of the cell cycle. This protein primarily exerts its effect by binding to and inhibiting which of the following transcription factors?
Explanation: Retinoblastoma is caused by mutations in the RB1 tumor suppressor gene. The Rb protein is a critical regulator of the G1/S cell cycle checkpoint. In its active, hypophosphorylated state, Rb binds to the E2F transcription factor, preventing it from activating the transcription of genes required for S-phase entry (e.g., cyclins, DNA polymerase). When a cell is stimulated to divide, cyclin/CDK complexes phosphorylate Rb, causing it to release E2F, thus allowing the cell cycle to proceed.
A 10-year-old boy presents with painless swelling on his jaw. A biopsy reveals a high-grade lymphoma. Cytogenetic analysis shows a translocation between chromosomes 8 and 14, t(8;14). The cells are described as having a 'starry sky' appearance on histology.
The genetic translocation in this patient's lymphoma leads to the overexpression of a gene that encodes which of the following types of protein?
Explanation: The clinical presentation and t(8;14) translocation are characteristic of Burkitt lymphoma. This translocation places the c-MYC proto-oncogene from chromosome 8 under the control of the strong immunoglobulin heavy chain gene enhancer on chromosome 14. MYC is a transcription factor that upregulates the expression of numerous genes involved in cell growth, proliferation, and metabolism, leading to uncontrolled cell division.
A 45-year-old woman with follicular lymphoma is noted to have high expression of the Bcl-2 protein in the neoplastic cells. This particular type of lymphoma is often characterized by a t(14;18) translocation.
The overexpression of Bcl-2 contributes to tumorigenesis by promoting which of the following 'hallmarks of cancer'?
Explanation: The B-cell lymphoma 2 (Bcl-2) protein is a key anti-apoptotic protein. It functions by inhibiting pro-apoptotic proteins like BAX and BAK, thereby stabilizing the mitochondrial membrane and preventing the release of cytochrome c, a critical step in the intrinsic pathway of apoptosis. In follicular lymphoma, the t(14;18) translocation places the BCL2 gene under the control of the strong immunoglobulin heavy chain promoter, leading to its overexpression. This makes the lymphoma cells resistant to programmed cell death (apoptosis), allowing them to accumulate and survive.
A 67-year-old man with a 50-pack-year smoking history presents with a 2-month history of a persistent cough, hemoptysis, and a 10-lb weight loss. A chest X-ray reveals a large central mass in the right lung. Laboratory studies are notable for a serum calcium level of 12.8 mg/dL (normal: 8.5-10.2 mg/dL). Serum parathyroid hormone (PTH) level is suppressed.
The hypercalcemia in this patient is most likely caused by the tumor's ectopic production of which of the following substances?
Explanation: This patient's presentation is classic for hypercalcemia of malignancy, a common paraneoplastic syndrome. Squamous cell carcinoma of the lung (strongly associated with smoking and central masses) is the most common cause. These tumors often secrete parathyroid hormone-related protein (PTHrP), which mimics the action of PTH on bone and kidney, leading to increased bone resorption and renal calcium reabsorption. The resulting hypercalcemia causes feedback suppression of the parathyroid glands, leading to low PTH levels.