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Diclofenac over the counter cream in an effort to reduce acne breakouts, which he has endured since age 12. But doctors are not convinced. And this time around the drug is showing little promise in the face of what scientists now call a "perfect storm" of factors: drug that's too potent, a marketing-savvy surgeon, culture of prescription painkiller abuse. "That's not going away," says Peter Hotez, an assistant clinical professor in dermatology at NYU's Langone Medical Center who is an active prescriber of topical retinoids. So-called systemic-only tretinoin products, which are applied topically, not only available, they're also prescribed by a lot of doctors. The most commonly prescribed topical retinoids are tazarotene, adapalene and tazarotene/tretinoin, all of which come in the form of topical creams and lotions (tazarotene is the only one of these creams that is FDA-approved). products, typically formulated with one of the antibiotics clindamycin, are given to the eye daily. They are absorbed by the body, then travel to dermis where they work slow the proliferation of skin cells. They also provide protection from photochemical damage; when these skinocytes are damaged from the sun, or in presence of acne, they start a vicious cycle of cell death, which causes a brown spot in the center of face, which in turn causes the skin to look white in the presence of sunlight. Systemic tretinoin products, though, are applied to the face and neck on a less frequent basis, typically every 3-4 weeks (about the same frequency as that of all prescription oral drug therapy). Because they are used on the face only, these products contain very small amounts of a potent tretinoin compound called tretinoin. Even so, the FDA has not given them a clear indication that their use is more effective than that of topical retinoids. "What we see as a real concern," Hotez says, "is that people could be getting too much or little, and we don't know how they respond." The best hope for tretinoin is a new class of chemical analogs produced by a gene editing technology known as CRISPR/Cas9. These new products would be far less potent and therefore better tolerated by dermatologists than the old topical retinoids, which have been approved for over 20 years. But the process hasn't been perfected. Just as it has with any gene editing, scientists and dermatologists still lack a clear understanding of what the effect this new technology will be because there isn't yet reliable evidence that the modified cells actually do anything. "If this were a blockbuster"

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