Misregulation of signaling pathways and diseases MCQs With Answer

Misregulation of signaling pathways underlies many human diseases, from cancer and metabolic disorders to neurodegeneration and chronic inflammation. For B. Pharm students, understanding cell signaling—receptor tyrosine kinases, GPCRs, JAK/STAT, PI3K/Akt/mTOR, Wnt, Notch and NF-κB—is essential for rational drug design, therapeutic targeting, and predicting adverse effects. Key concepts include oncogenic activation, loss of tumor suppressors (e.g., PTEN), feedback loops, pathway crosstalk, and resistance mechanisms to kinase inhibitors and monoclonal antibodies. This knowledge links molecular mechanisms to pharmacology, biomarker selection, and clinical outcomes, preparing students for roles in drug development, pharmacotherapy, and precision medicine. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which mechanism most commonly leads to constitutive activation of receptor tyrosine kinases (RTKs) in cancer?

• Overexpression or gene amplification of the RTK
• Increased ligand degradation
• Enhanced nuclear localization of RTKs
• Loss of RTK glycosylation

Correct Answer: Overexpression or gene amplification of the RTK

Q2. Loss of PTEN function primarily affects which signaling pathway, promoting cell survival and growth?

• MAPK/ERK pathway
• PI3K/Akt pathway
• JAK/STAT pathway
• Notch signaling

Correct Answer: PI3K/Akt pathway

Q3. A somatic activating mutation in RAS typically results in which of the following?

• Impaired GTP binding to RAS
• Constitutive GTP-bound active RAS signaling
• Increased RAS degradation by proteasomes
• Enhanced RAS tyrosine phosphorylation

Correct Answer: Constitutive GTP-bound active RAS signaling

Q4. Which therapeutic class directly inhibits ATP binding in kinases to block downstream signaling?

• Monoclonal antibodies
• Small-molecule tyrosine kinase inhibitors
• siRNA therapeutics
• Proteasome inhibitors

Correct Answer: Small-molecule tyrosine kinase inhibitors

Q5. Chronic activation of NF-κB signaling is most commonly associated with which pathological process?

• Increased apoptosis in neurons
• Chronic inflammation and oncogenesis
• Reduced cytokine production
• Enhanced insulin sensitivity

Correct Answer: Chronic inflammation and oncogenesis

Q6. Which mechanism best explains acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer?

• Increased drug absorption in the gut
• Secondary mutations in EGFR or activation of bypass pathways
• Loss of EGFR expression on the cell surface
• Enhanced antibody-dependent cytotoxicity

Correct Answer: Secondary mutations in EGFR or activation of bypass pathways

Q7. Aberrant Wnt/β-catenin signaling in colorectal cancer usually results from mutation of which component?

• Frizzled receptor overexpression
• APC tumor suppressor loss
• Excessive LRP5/6 phosphorylation
• GSK3β hyperactivation

Correct Answer: APC tumor suppressor loss

Q8. JAK/STAT pathway dysregulation leading to myeloproliferative neoplasms is commonly caused by which mutation?

• PIK3CA activating mutation
• JAK2 V617F mutation
• TP53 deletion
• BRCA1 frameshift mutation

Correct Answer: JAK2 V617F mutation

Q9. Which of the following is a key pharmacological strategy to target overactive GPCR signaling in disease?

• Use of orthosteric or allosteric GPCR antagonists
• Enhancing GPCR ligand synthesis
• Blocking GPCR nuclear import
• Inhibiting GPCR glycosylation

Correct Answer: Use of orthosteric or allosteric GPCR antagonists

Q10. Crosstalk between PI3K/Akt and MAPK pathways can reduce efficacy of single-agent inhibitors because:

• Both pathways always act independently
• Inhibition of one pathway often leads to compensatory activation of the other
• MAPK pathway is downstream of PI3K/Akt and cannot be reactivated
• PI3K inhibitors increase ligand degradation

Correct Answer: Inhibition of one pathway often leads to compensatory activation of the other

Q11. Notch signaling misregulation in T-cell acute lymphoblastic leukemia (T-ALL) is often due to:

• Loss-of-function mutations in Notch receptor
• Activating mutations in NOTCH1 enhancing transcriptional activity
• Excessive ubiquitination of Notch intracellular domain
• Complete absence of γ-secretase activity

Correct Answer: Activating mutations in NOTCH1 enhancing transcriptional activity

Q12. Which biomarker would most directly indicate activation of PI3K/Akt signaling in tumor samples?

• Phospho-Akt (Ser473) levels
• Total ERK protein levels
• p53 mRNA expression
• BRCA2 protein truncation

Correct Answer: Phospho-Akt (Ser473) levels

Q13. TGF-β signaling misregulation contributes to fibrosis primarily through which effect?

• Inhibition of extracellular matrix production
• Promotion of fibroblast activation and ECM deposition
• Induction of acute apoptosis in epithelial cells
• Suppression of collagen gene transcription

Correct Answer: Promotion of fibroblast activation and ECM deposition

Q14. A therapeutic monoclonal antibody targeting HER2 (e.g., trastuzumab) acts mainly by:

• Inhibiting HER2 gene transcription
• Blocking HER2 receptor dimerization and signaling and mediating ADCC
• Degrading HER2 mRNA
• Enhancing HER2 kinase activity

Correct Answer: Blocking HER2 receptor dimerization and signaling and mediating ADCC

Q15. Which cellular process commonly regulates signaling intensity by removing activated receptors from the membrane?

• Endocytosis and lysosomal degradation
• mRNA splicing
• SUMOylation in the nucleus
• Ribosomal stalling

Correct Answer: Endocytosis and lysosomal degradation

Q16. In neurodegenerative diseases, abnormal kinase signaling (e.g., GSK3β) can contribute to pathology by:

• Enhancing neurotransmitter uptake only
• Phosphorylating proteins like tau, promoting aggregation
• Preventing all post-translational modifications
• Increasing axonal transport efficiency

Correct Answer: Phosphorylating proteins like tau, promoting aggregation

Q17. Which resistance mechanism involves tumor cells bypassing a blocked pathway by activating an alternative receptor?

• Pharmacokinetic drug clearance
• Bypass signaling via receptor tyrosine kinase switching
• Complete loss of downstream effectors
• Enhanced drug-target binding affinity

Correct Answer: Bypass signaling via receptor tyrosine kinase switching

Q18. Proteasome inhibitors can influence signaling pathways by:

• Preventing protein synthesis entirely
• Blocking degradation of signaling regulators, altering pathway balance
• Enhancing ubiquitin ligase activity
• Directly phosphorylating transcription factors

Correct Answer: Blocking degradation of signaling regulators, altering pathway balance

Q19. Which assay is most appropriate to measure activation of MAPK/ERK signaling in cultured cells?

• ELISA for secreted cytokines only
• Western blot for phospho-ERK1/2
• qPCR of housekeeping genes
• Chromatin immunoprecipitation of tubulin promoters

Correct Answer: Western blot for phospho-ERK1/2

Q20. Constitutive activation of STAT proteins often leads to which change in cells?

• Reduced transcription of survival genes
• Enhanced transcription of proliferation and anti-apoptotic genes
• Increased proteasomal degradation of cytokine receptors
• Loss of nuclear localization signals in receptors

Correct Answer: Enhanced transcription of proliferation and anti-apoptotic genes

Q21. In targeted therapy development, why are combination treatments often preferred for pathway-driven cancers?

• They always reduce toxicity compared to single agents
• They can block primary and compensatory pathways, reducing resistance
• They increase the chance of tumor cells gaining growth advantage
• They eliminate the need for biomarkers

Correct Answer: They can block primary and compensatory pathways, reducing resistance

Q22. Which mutation type in a tumor suppressor gene most directly abolishes its negative regulation of signaling pathways?

• Synonymous mutation
• Nonsense or frameshift leading to truncated protein
• Intronic polymorphism far from splice sites
• Neutral missense in nonfunctional domain

Correct Answer: Nonsense or frameshift leading to truncated protein

Q23. mTOR inhibitors (e.g., rapamycin) primarily target which cellular process downstream of PI3K/Akt?

• DNA replication fidelity
• Protein synthesis and cell growth
• Membrane trafficking of receptors
• Microtubule polymerization

Correct Answer: Protein synthesis and cell growth

Q24. Epigenetic changes can alter signaling pathway output by:

• Changing DNA sequence of pathway genes
• Modulating expression of receptors, ligands, or regulators via methylation and histone marks
• Increasing ribosomal RNA mutation rates
• Directly phosphorylating kinases

Correct Answer: Modulating expression of receptors, ligands, or regulators via methylation and histone marks

Q25. Targeting cytokine signaling in autoimmune disease often focuses on which pathway mediator?

• STATs and JAK kinases
• Voltage-gated ion channels
• Mitochondrial DNA polymerase
• Extracellular matrix metalloproteinases only

Correct Answer: STATs and JAK kinases

Q26. Which adverse effect is commonly associated with VEGF pathway inhibitors used in cancer therapy?

• Hypertension and impaired wound healing
• Hyperglycemia and insulin resistance
• Severe immunosuppression leading to opportunistic infections
• Immediate hair loss due to keratinocyte apoptosis

Correct Answer: Hypertension and impaired wound healing

Q27. Biomarker-driven patient selection for targeted therapies is important because:

• All patients respond equally to targeted drugs
• It increases likelihood of clinical benefit and reduces unnecessary exposure
• It eliminates the need for pharmacovigilance
• It ensures drugs are always curative

Correct Answer: It increases likelihood of clinical benefit and reduces unnecessary exposure

Q28. Ubiquitin ligase loss can lead to enhanced signaling by:

• Promoting rapid receptor internalization
• Preventing degradation of signaling proteins, prolonging activity
• Increasing mRNA export from the nucleus
• Blocking receptor translation initiation

Correct Answer: Preventing degradation of signaling proteins, prolonging activity

Q29. Which approach can be used to overcome blood-brain barrier limitations for drugs targeting signaling in neurodegeneration?

• Use of larger antibody molecules without modification
• Designing small, lipophilic molecules or using carrier-mediated transport strategies
• Increasing systemic dose indefinitely
• Administering drugs that are exclusively hydrophilic

Correct Answer: Designing small, lipophilic molecules or using carrier-mediated transport strategies

Q30. Which statement best describes pathway-targeted precision medicine?

• Treating all patients with the same chemo regardless of tumor genetics
• Selecting therapies based on specific molecular alterations in signaling pathways to maximize efficacy
• Avoiding molecular diagnostics because they are not useful
• Using broad-spectrum antibiotics to target signaling defects

Correct Answer: Selecting therapies based on specific molecular alterations in signaling pathways to maximize efficacy

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