**Acknowledgements**

**8. Conclusions**

190 Human Skin Cancers - Pathways, Mechanisms, Targets and Treatments

ior modification.

Skin cancer is the most commonly diagnosed cancer in the U.S. and has become a major and growing public health problem. Despite numerous public health initiatives to promote sun safety, many Americans do not adhere to recommended guidelines to protect themselves from UV exposure. Given the long lag between UV induced skin damage and clinically apparent skin cancer, this reduces the perceived risk of UVR and does not encourage timely behav-

Our understanding of the pathogenesis of skin cancer at the molecular level has dramatically expanded within the past several years. Although there is still much to be learned about the underlying mechanisms of skin cancer pathobiology, advances in genetic sequencing have provided great insight into the ways in which effective tests may be developed for patient risk stratification of NMSC. This has since paved the way for pursuit of novel applications of this

Clinical biomarker discovery has led to revolutionary changes in medical screening, diagnosis, and target based therapies for a variety of cancers. In the era of precision medicine, individualized patient care is becoming increasingly important in all fields of medicine. While UVR has long been known to be a key risk factor for skin cancer development, increasing evidence has demonstrated that its role in carcinogenesis is likely multifactorial and involves multiple biologic pathways. Despite this, identification of cellular dysregulation in key regu-

Various types of biomarkers including DNA, RNA, and protein have been suggested for use in diagnostic and prognostic testing for various malignancies. Identification of individual biomarkers that produce consistent and reliable information on UV damage has posed a significant clinical challenge. We believe that a successful clinical test consisting of a panel of UV signature genes will provide the most sensitive and specific means for patient risk stratification of UV skin damage. Within NMSC research, RNA-based UV biomarkers currently exhibit the most promise for future clinical application given the multiple, reliable, and cost-

The current lack of skin cancer screening guidelines in the United States has resulted in a non-standardized approach to skin cancer screening and physician risk assessment. Thus, a UV biomarker-based screening test could provide an objective and evidence based method to determine which patients should receive regular skin cancer screening facilitate the identification of high risk individuals for dermatology referral and regular skin cancer screening. By encouraging early risk assessment, we believe that a biomarker-based diagnostic test will

Furthermore, translation of UV biomarker expression patterns into a risk score would hopefully offer quantitative and convincing evidence to alert susceptible individuals and encourage UV protective behaviors. Finally, development of a reliable UV biomarker panel could be used for other purposes such as testing the UV-protective effects of sunscreens. We believe this area of research deserves continued attention as the development of UV biomarker based tests has the potential to completely transform the preventative paradigm pertaining to skin cancer.

information, which have the potential to profoundly improve patient care.

latory pathways has provided insight into potential biomarkers of disease.

greatly improve skin cancer prevention and reduce skin cancer incidence.

effective modalities for RNA detection.

We thank the funding support by NIH/NIAMS grant K01AR064315, the Columbia University Herbert Irving Comprehensive Cancer Center (P30 CA013696), and the Center for Environmental Health in Northern Manhattan (P30 ES009089).
