Practicing dermatology in the region of America with the highest incidence per capita of skin cancer, particularly melanoma, the author has a significant interest in reducing the incidence of cancer by improving prevention as well as therapeutic modalities. These preventative technologies can also be expected to reduce the incidence of skin problems and diseases that share similar cutaneous anomalies to those that drive neoplasia. Understanding these anomalies that drive premalignant and malignant tumors can be expected to help optimize the function of sunscreen products.

Solar radiation damage includes UVA-induced immunosuppression that is coupled with dysplasia of epidermal cells induced by UVB. These activate an inflammatory cascade upregulating matrix metalloproteinases (MMPs) and gene transcription manipulation to produce the cancerous skin cells1. The UVL radiation damage is further enhanced by two cutaneous abnormalities that afflict most adults: a compromised stratum corneum permeability barrier (SCPB), and overt or occult chronic inflammation of the epidermis and dermis. Chronic inflammation becomes destructive when exaggerated MMP activity is coupled with reduced tissue inhibitor of MMPs (TIMPs), generating an imbalance of catabolism of cutaneous structural components2. Several of the nine MMPs fracture collagen, elastin, and glycosaminoglycans and upregulate transcription factors that activate keratinocyte and melanocyte dysplasia. Approximately 70% of American adults that are Fitzpatrick skin types I–III have a significantly reduced SCPB as determined by increased transepidermal water loss (TEWL)3, measured by evaporimeter. A persistent or recurrently damaged SCPB activates chronic inflammation and basal keratinocyte DNA synthesis to repair the injured skin4. This barrier compromise may be induced and/or exaggerated by exposure to multiple environmental insults including change of season to colder ambient temperatures, low and high ambient humidity variations, pollutant exposure, routine skin cleansing and skin care product regimens. Certain alcohols, vitamin A and C derivatives and hydroxy acids usually exist in marketed anti-aging products at barrier damaging and pro-inflammatory concentrations. Exposure to heavy metals such as nickel, gold, chromium, and lipid-lowering medications also inhibit repair of SCPB as well as damage it like UV‑light (UVL). Other barrier damaging environmental insults include prolonged air travel (>4–6 hours), severe emotional and physical stress, and severe dietary lipid restriction. Auto-immune diseases such as atopy, diabetes, lupus erythematosus, and certain other collagen vascular diseases are characterized by atrophic skin compromised SCPB and exaggerated chronic inflammation. Photoaging and eleven other cutaneous diseases and conditions are also characterized by these same two anomalies of a compromised SCPB and excessive chronic inflammation as listed in Table 15,6. The damaged SCPB allows the previously mentioned environmental insults to increase the amount and depth of mucocutaneous penetration by orders of magnitude. In turn, inflammation severity and depth are enhanced.

All sunscreen ingredients labeled by the FDA bind to stratum corneum corneocytes, lipids, and epidermal stratum granulosum cells. Therefore, a compromised stratum corneum is associated with significantly reduced binding of the sunscreen molecules at the active anatomic site. A further significant reduction of photoprotection occurs. It is intuitive that application of a barrier repairing product to the skin prior to sunscreen application would also be expected to significantly improve sunscreen protection. International regulatory bodies, including the FDA, recommend photoprotection when topically applied hydroxy acids, retinoids, and benzoyl peroxides are used chronically due to concerns of increased radiation injury, including neoplasia.

Hydration and transepidermal water loss

Table 1

Moisturization or hydration does not correlate with SCPB function; therefore, using any lotion or cream which by definition are more than 50% water phase, cannot be assumed to adequately repair a compromised SCPB. A truly repairing topical product needs to specifically incorporate SCPB repairing ingredients at the therapeutic concentrations. Ingredients documented to have barrier repair function are listed in Table 2. In an open clinical evaluation of over 100 commercially available products, only 11% of the moisturizing product improved SCPB function when assessing TEWL by evaporimeter7.

The importance of barrier function contributing to photoprotection was documented by applying a topical product containing a mix of only the three physiologic barrier lipids of the stratum corneum (cholesterol, ceramide and linoleic acid) without any sunscreen-specific ingredients. This formulation provided an SPF function of 5.28. Additionally, this semiocclusive product produced an 89.6% reduction of TEWL with one application 45 minutes following complete destruction of the stratum corneum, indicating nearly complete permeability barrier repair. In comparison, TEWL reduction is more than double the 43.1% reduction at the same time point by application of occlusive 100% pure white petrolatum3.

Table 2

The physiological lipid product was also statistically superior to prescription strength hydrocortisone in reducing cutaneous erythema and edema induced by three common insults: topical tretinoin, topical tazarotene, and UVB. A pilot study using the physiologic lipid formulation after laser resurfacing accelerated cutaneous healing by 80% compared to occlusive greasy antibiotic ointment or topical ointment. This improvement was defined by re-epithelialization and reduction of erythema as observed by a dermatologist that resides in another region of the US9.

Disrupting the stratum corneum permeability barrier from any insult initiates six inflammatory cascades including release of growth factors, histamine-1 activation, release of cytokines, activation of certain nuclear receptors, and bacterial activation of toll like receptors. Depending on the insult, the arachidonic acid cascade may be activated. The seventh is glycation induced inflammation, which is not released to SCPB. Repair of the SCPB is also complex with release of key ions, gene activation to upregulate repairing enzymes along with other groups of biologic response modifiers to upregulate lipid and protein synthesis4,5.

Controlling the seven inflammatory pathways that occur in damaged or diseased skin is also very important for long-term disease prevention. No synthetic ingredients block all of these but several herbal extracts modulate multiple pathways. These herbs are listed in Table 3. There are over 200 herbs known to have anti-inflammatory effects in skin3.


Certain sunscreen products on the market add anti-oxidant ingredients in an effort to boost photoprotective effectiveness based on an in vivo study that showed applying vitamin C and E plus ferulic acid enhances photoprotection10,11. However, in a more recent comparative open label human clinical trial, one to three antioxidants added to FDA approved sunscreen ingredients for commercial sunscreens did not enhance photoprotection beyond what the sunscreen ingredients themselves provided. In this same study, a seven component anti-inflammatory mix did significantly improve photoprotection beyond the sunscreen ingredients themselves. This study suggests that selecting a sunscreen with multiple anti-inflammatory, not just a few antioxidant ingredients, would provide enhanced sunscreen photoprotection1. This result would be expected since antioxidants affect only two of the seven inflammatory pathways.

The distinction between anti-inflammatory and antioxidant ingredients are important to understand due to all seven inflammatory pathways being modulated by the former. All antioxidants have at least a mild anti-inflammatory effect, but not all anti-inflammatories function via antioxidant effect. For example, aspirin, naprosyn and ibuprofen have no antioxidant effects, but are potent anti-inflammatories12.

Sunscreen efficacy

Table 3

Optimizing sunscreen efficacy can be a challenge if inadequate amounts of product are applied. The SPF value correlates with thickness of application in an exponential relationship. Formal SPF and UVA testing methods used to claim a product as a sunscreen requires a 20-patient clinical trial in which a specific thickness of the product is applied.  However, the average American only applies 25–40% of the recommended dose or thickness of application of the sunscreen product as recommended by the FDA. Tested SPF of 33 applied in a real-world dose or thickness of application on an average American provides a true protection factor of only 4.5. To maximize photoprotection one should apply a generous amount of sunscreen product in two applications about 30 minutes apart to cool, dry skin that will be exposed to the environment. The second application should be more than 30 minutes before sun, heat, and water exposure3.


In conclusion, to improve prevention of skin cancer, smart UVL protective products that address each of the anomalies induced by solar radiation should include:

  • Ingredients to optimize SCPB structure and function
  • Anti-inflammatory ingredients
  • Adequate doses of the photoprotective ingredients to optimally bind to intact stratum corneum and stratum granulosum by applying a thick enough layer.

As a corollary, a barrier repairing, anti-inflammatory smart sunscreen product will also be expected to maximize therapy and prevent exacerbations of the twelve cutaneous diseases and disorders previously listed in Table 1. Smart sun protective products are expected to be a valuable addition to a skin care practitioner’s therapeutic armamentarium. As scientific advances in medicine and physiology occur, strategies to prevent and treat diseases of our time including cancer must be adjusted to maximize quality of life of our patients, our clients and our loved ones.