Abstract
In 2025, seven fluorine-containing anticancer agents received approval from the US Food and Drug Administration, underscoring the continued and growing impact of strategic fluorination in modern oncology drug design. These newly authorized therapies represent a diverse portfolio spanning a broad spectrum of malignancies, molecular targets, and innovative mechanisms of action, further validating fluorine’s unique ability to enhance drug performance. Sunvozertinib (Zegfrovy®) was approved for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring specific EGFR mutations. The combination of defactinib and avutometinib (Avmapki®) provides a much-needed targeted option for patients with KRAS-mutated recurrent low-grade serous ovarian cancer, addressing a historically challenging disease setting. Imlunestrant (Inluriyo®) offers a next-generation selective estrogen receptor degrader (SERD) as an effective endocrine therapy for estrogen receptor-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. Ziftomenib (Komzifti®) enables precision therapy for adults with relapsed or refractory (AML) carrying susceptible NPM1 mutations, representing a significant advancement in targeted hematologic oncology.Datopotamab deruxtecan (Datroway®), a novel TROP2-directed antibody–drug conjugate (ADC) with a topoisomerase I inhibitor payload, expands treatment options for previously treated hormone receptor-positive, HER2-negative metastatic breast cancer and for certain TKI-experienced NSCLC populations. Taletrectinib
(Ibtrozi®), a potent next-generation ROS1 tyrosine kinase inhibitor, received approval for ROS1-positive NSCLC in both TKI-naïve and TKI-experienced patients, offering improved central nervous system penetration and activity against resistant mutations.Collectively, these seven agents vividly illustrate the remarkable versatility of fluorine incorporation in enhancing molecular potency, metabolic stability, binding selectivity, and overall pharmacokinetic performance across vastly different therapeutic modalities — from small-molecule kinase inhibitors and degraders to complex antibody–drug conjugates. The strategic placement of fluorine atoms or fluorinated groups in these molecules often leads to improved lipophilicity, stronger target engagement, reduced clearance, and better safety profiles.For each compound, we provide a comprehensive integrated discussion covering its discovery history, detailed biological mechanism of action, primary therapeutic applications, recommended clinical administration and dosing regimens, the specific role of fluorination in optimizing its pharmacological and physicochemical properties, as well as the detailed chemical synthesis routes employed in its industrial-scale production.
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