gdc-0449 and Carcinoma--Squamous-Cell

Although surgical intervention remains the standard of care for nonmelanoma skin cancer, other treatment modalities have been studied and used. Nonsurgical treatment methods include cryotherapy, topical medications, photodynamic therapy, radiation therapy, Hedgehog pathway inhibitors, programmed cell death protein 1 inhibitors, and active nonintervention. Despite the favorable efficacy of surgical treatment methods, many factors, including but not limited to patient age, preference, and severity of disease, must be taken into consideration when choosing the most appropriate, patient-centered treatment approach.

Topics: Administration, Cutaneous; Anilides; Antineoplastic Agents; Antineoplastic Agents, Immunological; Biphenyl Compounds; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cryosurgery; Cyclooxygenase Inhibitors; Diclofenac; Diterpenes; Fluorouracil; Humans; Imiquimod; Photochemotherapy; Programmed Cell Death 1 Receptor; Pyridines; Radiotherapy; Skin Neoplasms; Watchful Waiting

Locally advanced and metastatic nonmelanoma skin cancer (NMSC) not amenable to surgical resection requires a different approach to therapy.. To review the efficacy and adverse effects of emerging treatment options for locally advanced and metastatic NMSC.. A comprehensive search on PubMed was conducted to identify relevant literature investigating the role of program cell death 1 (PD-1) inhibitor, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and Hedgehog pathway inhibitors in the treatment of NMSC.. PD-1 inhibitor and CTLA-4 inhibitor have shown promising efficacy with tolerable side-effect profiles in the treatment of NMSC, although the number of cases reported is limited. Currently, 3 larger-scale clinical trials are investigating PD-1 inhibitor therapy for NMSC. Similarly, EGFR inhibitor demonstrated marginal success in unresectable cutaneous squamous cell carcinomas. Hedgehog pathway inhibitors were approved by the US FDA for treatment of locally advanced and metastatic basal cell carcinomas and have shown favorable efficacy. Common adverse effects included muscle spasm, alopecia, and dysgeusia.. Systemic therapies including PD-1 inhibitors and CTLA-4 inhibitors have demonstrated early promising results for difficult-to-treat NMSC. Future studies are necessary to optimize treatment outcome.

Topics: Anilides; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Biphenyl Compounds; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cetuximab; CTLA-4 Antigen; ErbB Receptors; Hedgehog Proteins; Humans; Ipilimumab; Nivolumab; Programmed Cell Death 1 Receptor; Pyridines; Skin Neoplasms

Non-melanoma skin cancers are the most common malignancy in humans, with a basal/squamous cell carcinoma incidence ratio of 4:1 in immunocompetent patients. Basal cell carcinoma rarely metastasizes but commonly causes significant local tissue destruction and disfigurement, whereas squamous cell carcinoma is associated with a substantial risk of recurrence and metastasis; the prognosis in metastatic patients is poor. Surgical approaches give a cure rate greater than 90% if appropriately applied, on the basis of the characteristics of the primary tumors and of the patients, but in selected cases, medical treatment (5-fluorouracil, imiquimod, diclofenac and, more recently, ingenol mebutate) is preferable to invasive procedures and provides a good chance of cure, with generally excellent cosmetic outcomes. In case of advanced and metastatic non-melanoma skin cancer, newly developed molecularly targeted therapy represents a reasonably promising alternative to classical cytostatics. In particular, the monoclonal antibody cetuximab, directed against the epidermal growth factor receptor, is effective and well-tolerated in squamous cell carcinoma patients. Moreover, the recent identification of mutations in the Hedgehog signaling pathway in basal cell carcinoma lead to the development of the smoothened Hedgehog pathway inhibitor vismodegib, that was recently approved for the treatment of locally advanced or metastatic basal cell carcinoma. In this review we provide an overview of the molecular pathways involved in NMSC pathogenesis, focusing on the mechanisms of action, indications, efficacy, side effects and contraindications of new medical treatments that specifically tackle molecular targets of these pathways.

Topics: Anilides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cetuximab; Clinical Trials as Topic; Humans; Molecular Targeted Therapy; Neoplasm Metastasis; Prognosis; Pyridines; Signal Transduction; Skin Neoplasms

Nonmelanoma skin cancer (NMSC) is the most common cancer in patients and includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Treatments useful for SCC and BCC include surgical, topical, and in advanced cases systemic chemo-radiation. This review of the literature aims to describe previous and current treatment options for oral therapy in locally advanced and metastatic NMSC otherwise unamenable to standard treatment. Oral Smoothened (Smo) inhibitors Vismodegib, Sonidegib, and Taladegib have shown to be effective in several trials. Oral tyrosine kinase inhibitors Erlotinib and Gefitinib, which target epidermal growth factor receptor (EGFR), have early supporting data and are currently undergoing large multicenter trials. Other less studied oral therapies which have shown at least partial efficacy include 5-Fluorouracil, capecitabine, and picropodophyllin. In vitro studies have elucidated new targets for dual combination oral therapy targeting both EGFR and insulin-like growth factor 1 receptor (IGF-1R). It is important to stratify treatment options based on patient risk of advanced disease, failure of conservative treatment, and ill-tolerated intravenous chemotherapy adverse events. Oral therapy in NMSC is useful in high risk patients with recurrent and aggressive disease who may not tolerate other systemic therapies.

Topics: Administration, Oral; Anilides; Antineoplastic Agents; Biphenyl Compounds; Capecitabine; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; ErbB Receptors; Erlotinib Hydrochloride; Fluorouracil; Gefitinib; Hedgehog Proteins; Molecular Targeted Therapy; Phthalazines; Podophyllotoxin; Pyridines; Quinazolines; Receptor, IGF Type 1; Retinoids; Skin Neoplasms; Tumor Burden

Epithelial skin cancers (ESCs), namely basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), are considered common skin malignancies, with rising incidence rates over the past few decades. A subgroup of patients with ESC present with advanced and 'difficult'-to-treat tumours, including locally advanced and metastatic tumours. Currently, there is no widely accepted staging system for locally advanced ESCs, while metastatic BCCs and SCCs share a staging system. Therefore, selecting an appropriate therapeutic regimen for these patients may be difficult.. The purpose of this review is to highlight the pharmacologic treatment options for advanced ESCs. These include 'conventional' chemotherapeutic regimens such as 5-fluorouracil, cisplatin, vincristine, bleomycin and doxorubicin and newer, more 'targeted' therapies.. Vismodegib, a Hedgehog (Hh) inhibitor, was recently approved for the treatment of advanced BCC showing a good efficacy rate and a relatively well-tolerated safety profile in clinical studies. In addition, a number of hedgehog inhibitors are now in Phase I and II trials of advanced BCC demonstrating encouraging results. Phase II studies with epithelial growth factor receptor inhibitors, such as cetuximab, gefitinib, panitimumab and erlotinib have been conducted in patients with advanced SCCs, used either as monotherapy or in combination with chemotherapy. However, there is still much knowledge to be gained about the treatment efficacies, optimal treatment durations, mechanisms of drug tolerance, adverse events and the ways in which these therapies influence patient outcomes and quality of life.

Topics: Anilides; Antibodies, Monoclonal; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drug Resistance, Neoplasm; ErbB Receptors; Erlotinib Hydrochloride; Gefitinib; Humans; Molecular Targeted Therapy; Pyridines; Quality of Life; Quinazolines; Skin Neoplasms; Treatment Outcome

Topics: Aged, 80 and over; Anilides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Combined Modality Therapy; Compassionate Use Trials; Face; Follow-Up Studies; Humans; Male; Neoplasm Invasiveness; Neoplasm Staging; Pyridines; Radiotherapy, Adjuvant; Risk Assessment; Skin Neoplasms; Terminally Ill; Treatment Outcome

Over the past two decades, advances in the fields of cancer genetics and molecular biology have elucidated molecular pathways that cause numerous cutaneous malignancies. This in turn has spurred the rational design of molecularly targeted therapies. In this review, we discuss the molecular pathways critical to the development of nonmelanoma skin cancers and the novel pharmacologic agents that target them. Included is a review of vismodegib for basal cell carcinoma, cetuximab for squamous cell carcinomas, imatinib for dermatofibrosarcoma protuberans, and sirolimus for Kaposi's sarcoma.

Topics: Anilides; Antibiotics, Antineoplastic; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Benzamides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cetuximab; Dermatofibrosarcoma; Humans; Imatinib Mesylate; Piperazines; Pyridines; Pyrimidines; Sarcoma, Kaposi; Sirolimus; Skin Neoplasms

Surgical treatment remains the standard of care for nonmelanoma skin cancer and is successful for the vast majority of patients with these tumors. The treatment of patients with metastatic or unresectable nonmelanoma skin cancer, however, has until recently been based solely on traditional methods of chemotherapy and radiation. However, these methods have high rates of treatment failure, morbidity, and mortality, and alternative treatment modalities for patients with aggressive or advanced disease are needed. As in other areas of cancer therapeutics, recent research elucidating the molecular basis of cancer development, and the subsequent arrival of targeted molecular inhibitors for cancer therapy, have been met with much excitement. In this review, we seek to illuminate recent developments and future possibilities in the use of targeted molecular inhibitors for treatment of advanced squamous cell carcinoma, basal cell carcinoma, and dermatofibrosarcoma protuberans.

Topics: Anilides; Antineoplastic Agents; Benzamides; Carcinoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermatofibrosarcoma; ErbB Receptors; Head and Neck Neoplasms; Humans; Imatinib Mesylate; Molecular Targeted Therapy; Neoplasms, Squamous Cell; Piperazines; Pyridines; Pyrimidines; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck

Topics: Anilides; Antineoplastic Agents; Antineoplastic Agents, Immunological; Biphenyl Compounds; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drugs, Investigational; Humans; Molecular Targeted Therapy; Pyridines; Skin Neoplasms

We report a case of a 60-year-old man who was a former cigar smoker with a slow-growing, large exophytic left shoulder mass (15 cm in diameter) and later found to have left axillary lymphadenopathy. Fine needle aspirate biopsy of the left shoulder mass revealed squamous cell carcinoma (SCC). However, pathology of the enlarged left axillary lymph node was reported as metastatic adenocarcinoma. The patient underwent surgical resection of the shoulder mass which comprised of SCC (>95%) and adenoid basal cell carcinoma (BCC) as a second component of the tumour. The BCC had identical histology as the metastatic carcinoma in the left axillary lymph node. Therefore, diagnosis was revised as cutaneous collision tumour with metastatic BCC. Six months later following adjuvant radiation therapy, the patient was diagnosed with metastatic BCC in the right lung. Stereotactic body radiation therapy (SBRT) and a selective hedgehog pathway inhibitor vismodegib were given with only limited efficacy. Clinical trial registration number NCT03132636.

Topics: Anilides; Axilla; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Hedgehog Proteins; Humans; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Pyridines; Radiosurgery; Radiotherapy, Adjuvant; Skin Neoplasms; Treatment Outcome

Vismodegib, an inhibitor of the Hedgehog signaling pathway, is an approved drug for monotherapy in locally advanced or metastatic basal cell carcinoma (BCC). Data on combined modality treatment by vismodegib and radiation therapy, however, are rare. In the present study, we examined the radiation sensitizing effects of vismodegib by analyzing viability, cell cycle distribution, cell death, DNA damage repair and clonogenic survival in three-dimensional cultures of a BCC and a head and neck squamous cell carcinoma (HNSCC) cell line. We found that vismodegib decreases expression of the Hedgehog target genes glioma-associated oncogene homologue (GLI1) and the inhibitor of apoptosis protein (IAP) Survivin in a cell line- and irradiation-dependent manner, most pronounced in squamous cell carcinoma (SCC) cells. Furthermore, vismodegib significantly reduced proliferation in both cell lines, while additional irradiation only slightly further impacted on viability. Analyses of cell cycle distribution and cell death induction indicated a G1 arrest in BCC and a G2 arrest in HNSCC cells and an increased fraction of cells in SubG1 phase following combined treatment. Moreover, a significant rise in the number of phosphorylated histone-2AX/p53-binding protein 1 (γH2AX/53BP1) foci in vismodegib- and radiation-treated cells was associated with a significant radiosensitization of both cell lines. In summary, these findings indicate that inhibition of the Hedgehog signaling pathway may increase cellular radiation response in BCC and HNSCC cells.

Topics: Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Line, Tumor; Combined Modality Therapy; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Hedgehog Proteins; Histones; Humans; Organ Specificity; Pyridines; Radiation-Sensitizing Agents; Signal Transduction; Skin Neoplasms; Survivin; Tumor Suppressor Protein p53; Zinc Finger Protein GLI1

Vismodegib is a first-in-class agent targeting the hedgehog signaling pathway for treatment of patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC. There have been concerns about the development of squamous cell carcinoma (SCC) in patients treated with this drug.. We sought to determine whether treatment with vismodegib is associated with an increase in the risk of cutaneous SCC.. In this retrospective cohort study, patients treated with vismodegib as part of phase I and II clinical studies were compared with participants from the University of California, San Francisco, Nonmelanoma Skin Cancer Cohort who received standard therapy for primary BCC. In total, 1675 patients were included in the analysis, and the development of SCC after vismodegib exposure was assessed.. The use of vismodegib was not associated with an increased risk of subsequent development of SCC (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28-1.16). Covariates including age, sex, history of previous nonmelanoma skin cancer, and number of visits per year were significantly associated with the development of SCC.. A limitation of the study was that a historic control cohort was used as a comparator.. Vismodegib was not associated with an increased risk of subsequent SCC when compared with standard surgical treatment of BCC.

Topics: Age Factors; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Female; Humans; Male; Middle Aged; Neoplasms, Second Primary; Office Visits; Pyridines; Retrospective Studies; Risk Factors; Sex Factors; Skin Neoplasms

The hedgehog signalling pathway (Hh) is frequently active in head and neck squamous cell carcinoma (HNSCC). Overexpressed Hh associates with poor prognosis. The Hh inhibitor vismodegib targets smoothened, and based on molecular data, may prevent resistance to EGFR targeting.. To elucidate potential roles of vismodegib in HNSCC therapy, its sole effects and those combined with cisplatin, docetaxel, and cetuximab on HNSCC cell lines were assessed by MTT metabolisation and BrdU incorporation. Colony formation (CF) of primary HNSCC cells was studied utilizing the FLAVINO-protocol. Combinatory effects were analysed regarding antagonism, additivity or synergism. Associations between the ex vivo detected mode of action of vismodegib with other treatments related to patient characteristics were assessed and progression-free survival (PFS) in patient groups compared using Kaplan-Meier curves.. Vismodegib suppressed BrdU incorporation significantly stronger than MTT turnover; CF was significantly inhibited at ≥20 µM vismodegib while concentrations <20 µM acted hormetic. Combining 20 µM vismodegib plus docetaxel (T), cisplatin (P), and cetuximab (E), additively enhanced anti-tumoral activity in HNSCC samples from patients with superior PFS highlighting a potential role for ex-vivo testing of this combination for use as a prognostic classifier.. We provide ex-vivo evidence for vismodegib's potential in HNSCC therapies, especially if combined with cetuximab, cisplatin and docetaxel.

Topics: Anilides; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Cetuximab; Dose-Response Relationship, Drug; Drug Interactions; ErbB Receptors; Female; Head and Neck Neoplasms; Hedgehog Proteins; Humans; Male; Pyridines; Signal Transduction; Squamous Cell Carcinoma of Head and Neck

Smoothened inhibitors (SIs) are a new type of targeted therapy for advanced basal cell carcinoma (BCC), and their long-term effects, such as increased risk of subsequent malignancy, are still being explored.. To evaluate the risk of developing a non-BCC malignancy after SI exposure in patients with BCC.. A case-control study at Stanford Medical Center, an academic hospital. Participants were higher-risk patients with BCC diagnosed from January 1, 1998, to December 31, 2014. The dates of the analysis were January 1 to November 1, 2015.. The exposed participants (cases) comprised patients who had confirmed prior vismodegib treatment, and the nonexposed participants (controls) comprised patients who had never received any SI. Because vismodegib was the first approved SI, only patients exposed to this SI were included.. Hazard ratio for non-BCC malignancies after vismodegib exposure, adjusting for covariates.. The study cohort comprised 180 participants. Their mean (SD) age at BCC diagnosis was 56 (16) years, and 68.9% (n = 124) were male. Fifty-five cases were compared with 125 controls, accounting for age, sex, prior radiation therapy or cisplatin treatment, Charlson Comorbidity Index, clinical follow-up time, immunosuppression, and basal cell nevus syndrome status. Patients exposed to vismodegib had a hazard ratio of 6.37 (95% CI, 3.39-11.96; P < .001), indicating increased risk of developing a non-BCC malignancy. Most non-BCC malignancies were cutaneous squamous cell carcinomas, with a hazard ratio of 8.12 (95% CI, 3.89-16.97; P < .001), accounting for age and basal cell nevus syndrome status. There was no significant increase in other cancers.. Increased risk for cutaneous squamous cell carcinomas after vismodegib therapy highlights the importance of continued skin surveillance after initiation of this therapy.

Topics: Adult; Aged; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Case-Control Studies; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Pyridines; Risk; Skin Neoplasms

Topics: Aged; Anilides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Combined Modality Therapy; Facial Dermatoses; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mohs Surgery; Pyridines

Topics: Anilides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Case-Control Studies; Humans; Pyridines; Skin Neoplasms

Topics: Anilides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Case-Control Studies; Humans; Pyridines; Skin Neoplasms

Topics: Anilides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Pyridines; Skin Neoplasms

Basal cell carcinoma (BCC) is the most common cancer in humans. Vismodegib, a Hedgehog pathway inhibitor, has proved its effectiveness in treating non-resectable advanced BCC.. However, its action on squamous cell carcinoma (SCC) is unknown. We present three SCC cases developed into BCC in vismodegib-treated patients.. We have described three cases of patients developing SCC during treatment by vismodegib for BCC.. Patient 1 was treated with vismodegib for five facial BCC. Due to the progression of one of the lesions at month 3 (M3), a biopsy was performed and showed SCC. Patient 2 was treated with vismodegib for a large facial BCC. A biopsy was performed at M2 on a BCC area not responding to treatment and showed SCC. Patient 3 was treated with vismodegib for a BCC on the nose. Due to vismodegib ineffectiveness, a biopsy was performed and showed SCC.. Two similar cases have been described in the literature. This could be due to the appearance of the squamous contingent of a metatypical BCC or to the squamous differentiation of stem cells through inhibition of the hedgehog pathway.. In practice, any dissociated response of a BCC to vismodegib should be biopsied.

Topics: Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Facial Neoplasms; Female; Humans; Male; Middle Aged; Neoplasms, Second Primary; Pyridines; Skin Neoplasms

Vismodegib therapy achieves a breakthrough in patients with locally advanced basal cell carcinoma (BCC). Yet, long-term safety of hedgehog pathway inhibitors remains to be established, while drug resistance is becoming a new challenging issue.. We report the case of a 90-year-old male initially referred for a locally advanced BCC of the nose. He had been previously treated by topical 5-fluorouracil for an adjacent microinvasive squamous cell carcinoma (SCC), with complete clinical response. Afterwards, vismodegib was initiated to treat his BCC. At week 16, both tumor and tumor ulceration obviously progressed. Palliative rhinectomy was performed. Histological examination found a deeply invasive SCC.. Although our case must be interpreted with caution, a role of vismodegib as a promoter of cutaneous SCC should be considered, consistently with recently published evidence. Physicians should perform new biopsies whenever in doubt about new and/or progressive skin lesions in patients receiving hedgehog pathway inhibitors.

Topics: Aged, 80 and over; Anilides; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Facial Neoplasms; Fluorouracil; Humans; Male; Nose Neoplasms; Pyridines; Skin Neoplasms

Topics: Anilides; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; DNA, Neoplasm; Drug Resistance, Neoplasm; Exome; Female; Humans; Lymphatic Metastasis; Middle Aged; Mutation; Pyridines; Sequence Analysis, DNA; Skin Neoplasms

Topics: Aged, 80 and over; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Neoplasms, Second Primary; Pyridines; Skin Neoplasms

Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment.. The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected.. These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.

Topics: Adult; Anilides; Biopsy; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Pyridines; Skin Neoplasms

Topics: Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Recurrence, Local; Phenotype; Pyridines; Skin Neoplasms

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