Which mechanism explains the phenomenon of 'oncogene addiction' seen in certain cancers such as BCR-ABL-driven CML or EGFR-mutant lung adenocarcinoma?

• A The cancer cell has accumulated so many mutations it cannot survive without the oncogene's continuous signaling
• B The normal cell of origin also requires this pathway, so the tumor is not truly dependent on it
• C The oncogene mutation causes genomic instability requiring other mutations for survival
• D Tumor cells rewire signaling so that a single oncogene dominates survival pathways, making them exquisitely sensitive to its inhibition ✓

Explanation

Oncogene addiction describes the paradoxical dependence of cancer cells — which have many mutations — on a single dominant oncogene for survival. Cancer cells rewire their signaling so that a single activated pathway (BCR-ABL, EGFR, BRAF) dominates and suppresses alternative survival pathways; removing it collapses multiple networks simultaneously. This is the basis for dramatic responses to targeted therapies. It is not due to genomic instability per se but to pathway rewiring that normal cells have not undergone.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.