gdc-0449 and Keratosis--Actinic

Actinic keratosis (AK) is a common premalignant skin lesion that is frequently treated by cryosurgery. Basal cell carcinoma is the most common malignancy of man, and early-stage lesions are usually cured via surgery. Advanced basal cell carcinoma may require more extensive surgery resulting in deformity, and many advanced lesions cannot be treated surgically. Several recent developments have improved therapeutic options for both conditions. Cryosurgery is still a mainstay of treatment for AK, but the introduction of effective topical agents, imiquimod cream and ingenol mebutate, has provided alternatives to cryosurgery. For advanced basal cell carcinoma, the small-molecule inhibitor vismodegib has proven to be an effective therapy for lesions that are not amenable to surgery and has demonstrated ability to achieve dramatic improvement in advanced, potentially disfiguring cancer.

Topics: Aminoquinolines; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Cryosurgery; Diterpenes; Humans; Imiquimod; Keratosis, Actinic; Mutation; Patched Receptors; Pyridines; Receptors, Cell Surface; Skin Neoplasms; Treatment Outcome

The regrowth of a tumor after complete clinical response and the development of keratinocytic neoplasms while patients are still undergoing continuous vismodegib have stressed the importance of the accurate monitoring to detect recurrences earlier and ensure the best possible outcome.. The objective of this study was to determine the role of reflectance confocal microscopy (RCM) in monitoring the response of locally advanced basal cell carcinoma (laBCC) to vismodegib and to discard secondary resistance.. Seven patients presenting with nine laBCC, were prospectively included and their response to this drug was assessed by means of clinical examination, dermoscopy, and RCM. The study was conducted at the Melanoma Unit in Hospital Clinic of Barcelona, between June 2012 and March 2013.. Histologically confirmed lesion 10 mm or larger in diameter for which surgery was contraindicated and radiation therapy was inappropriate. The median patient age was 73 years and the most common histological type was infiltrating BCC. RCM allowed the identification of residual tumor in two lesions and to confirm complete response in the other four cases. Two patients developed new lesions within the tumor bed, they were assessed by RCM showing features of actinic keratosis which were confirmed by histopathology.. The use of in vivo RCM allowed the characterization of the dynamic morphologic changes in tumor response helping to better define partial response and to differentiate it from secondary resistance. Another interesting observation was the recognition of a phenomenon characterized by the development of keratinocytic neoplasms within the tumor bed.

Topics: Aged; Aged, 80 and over; Anilides; Carcinoma, Basal Cell; Dermoscopy; Female; Humans; Intravital Microscopy; Keratinocytes; Keratosis, Actinic; Male; Microscopy, Confocal; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Pyridines; Skin Neoplasms; Spain

With the incidence of nonmelanoma skin cancer on the rise, current prevention methods, such as the use of sunscreens, have yet to prove adequate to reverse this trend. There has been considerable interest in identifying compounds that will inhibit or reverse the biochemical changes required for skin cancers to develop, either by pharmacologic intervention or by dietary manipulation. By targeting different pathways identified as important in the pathogenesis of nonmelanoma skin cancers, a combination approach with multiple agents or the addition of chemopreventative agents to topical sunscreens may offer the potential for novel and synergistic therapies in treating nonmelanoma skin cancer.

Topics: Anilides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; Cell Transformation, Neoplastic; Cyclooxygenase 2 Inhibitors; Diet, Fat-Restricted; DNA Repair Enzymes; Eflornithine; Flavonoids; Genistein; Humans; Keratosis, Actinic; Lycopene; Phenols; Photochemotherapy; Polyphenols; Pyridines; Retinoids; Skin Neoplasms; Sunscreening Agents; Ultraviolet Rays