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Table 3 Examples of sporadic and hereditary conditions and of somatic mosaic non-malignant conditions that have been treated successfully in animal models or in patients by targeting underlying “oncogenic” drivers using drugs, some of which were developed for cancer

From: The paradox of cancer genes in non-malignant conditions: implications for precision medicine

ConditionUnderlying molecular defectTherapyResult of therapyCommentsFDA-approved drug: cancers treated
Sporadic conditions
 Rheumatoid arthritisTP53 mutationsTocilizumab, which is an anti-IL-6 receptor antibodyDecreased incidence of flares, better disease control [169]Efficacy in humans; TP53 mutations are known to increase IL-6, which mediates inflammation [142]None
 Desmoid tumorsCTNNB1 mutationsCOX-2 inhibitors and sorafenibTumor regression [5, 145, 146]Efficacy in humans; COX-2 inhibitors and sorafenib can abrogate the activation of the WNT pathway by CTNNB1 alterations [13, 41, 42]COX-2 inhibitors: none
Sorafenib: renal cell carcinoma, hepatocellular carcinoma
 Inflammatory myofibroblastic tumorsALK rearrangementsCrizotinibSustained objective responses [30]Efficacy in humans; crizotinib is a potent ALK inhibitorNon-small cell lung cancer
 Schnitzler syndromeMYD88 L265P mutationAnakinra, which is an IL-1 antagonistComplete remission of disease [170]Efficacy of anankinra in humansNone
 Neurofibromatosis 1NF1 mutationsMEK inhibitor selumetinib71% partial response rate for inoperable plexiform neurofibromas [92]FDA granted breakthrough status for selumetinib for NF1 in 2019None
Hereditary and somatic mosaic conditions
 CLOVES syndromeMosaic gain-of-function PIK3CA alterationsAlpelisib, which is PIK3CA inhibitorImproved disease-related symptoms [113]Efficacy in humansHormone-positive, HER2-negative breast cancer
 Central conducting lymphatic anomalyGain-of-function ARAF mutations (MEK or mTOR pathway)Sirolimus (mTOR inhibitor) or trametinib (MEK inhibitor)Resolution of chylous output over the course of a week with removal of chest tube with sirolimus (n = 1) [53]
Dramatic clinical improvement, with remodeling of the patient’s lymphatic system and resolution of the lymphatic edema, marked improvement in pulmonary function tests, cessation of supplemental oxygen requirements and near normalization of daily activities with trametinib (n = 1) [51]
Efficacy in humansSirolimus: none
Trametinib: melanoma
 Fibroadipose hyperplasiaPIK3CA mutationsSirolimus (mTOR inhibitor)Stabilization or improvement in disease in patients [115, 171]Efficacy in humansNone
 AchondroplasiaFGFR3 mutationsFGFR3 inhibitor in mouse modelsRestored size of embryonic achrondroplastic femurs in animals [172]Animal model efficacyNone