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In colorectal cancer treated with anti-EGFR antibodies, activating RAS mutations can be detected in circulating tumor DNA months before radiographic progression, indicating that molecular resistance precedes clinical failure ( 2.3 Genetic determinants of tumor heterogeneity 2.3.1 Somatic mutations and clonal architecture Genetic heterogeneity originates from the elevated mutational burden characteristic of malignant cells, driven by defects in genome maintenance pathways, replication stress, oncogene-induced DNA damage, and exposure to endogenous and exogenous mutagens

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Most patients can significantly reduce symptoms without discontinuing their medicine, which is important given the substantial metabolic benefits these drugs provide

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