Precision dermatology uses individualized dermatologic disease-directed targeted
therapy (D3T2) for the management of
dermatoses and for the evaluation and
therapy of cutaneous
malignancies. Personalized/precision strategies are based on
biomarkers that are most frequently derived from tissue transcriptomic expression or genomic sequencing or from circulating
cytokines. For instance, the pathologic diagnosis of a pigmented lesion and determining the prognosis of a malignant melanocytic
neoplasm can be enhanced by genomic/transcriptomic analysis. In addition to biopsy, innovative techniques have been developed for obtaining transcriptomes in skin conditions; as an example, patches can be applied to a
psoriasis plaque for a few minutes to capture the epidermis/upper dermis transcriptome.
Atopic dermatitis and
prurigo nodularis may also be candidate conditions for precision dermatology. Precision dermatology has a role in managing
melanoma and nonmelanoma
skin cancers and rare cutaneous
tumors-such as
perivascular epithelioid cell tumor (
PEComa)-that can originate in or metastasize to the skin. For instance, advanced/metastatic
basal cell carcinomas can be treated with Hedgehog inhibitors (
vismodegib and
sonidegib) targeting the smoothened (SMO) or patched 1 (PTCH1) gene alterations that are a hallmark of these
cancers and activate the Hedgehog pathway. Advanced/metastatic basal and cutaneous
squamous cell cancers often have a high
tumor mutational burden (which predicts
immunotherapy response); immune checkpoint blockade with
cemiplimab, a
programmed cell death protein 1 (PD1) inhibitor, is now approved for these
malignancies. Gene expression profiling of primary cutaneous
squamous cell carcinoma can identify those individuals at high risk for subsequent
metastases. In the realm of rare
neoplasms,
PEComas-which can originate in the skin, albeit uncommonly-have
tuberous sclerosis complex 1 (TSC1)/
tuberous sclerosis complex 2 (TSC2) gene alterations, which activate
mammalian target of rapamycin (mTOR) signaling, and can be suppressed by nab-
sirolimus, now approved for this condition. In summary, precision dermatologic techniques/strategies are an important emerging approach for evaluation and management of skin disorders and cutaneous
neoplasms, and may serve as a paradigm for the application of
precision medicine beyond dermatology.