Therapy For Nonmelanoma Skin Cancer Research Articles

Radiation Therapy for Non-Melanoma Skin Cancer: A Study of 63 Cases

Cutaneous carcinomas are the most common skin cancers. Our work aims to identify the epidemiological and clinicopathological characteristics of cutaneous carcinomas, especially squamous cell carcinomas and basal cell carcinomas, treated and monitored at the Oncoradiotherapy Department of the Mohammed VI University Hospital of MARRAKECH, treated with radiotherapy, and to evaluate their efficacy and tolerance. Our study is retrospective and descriptive. We collected data from 63 patients treated and monitored between 2019 and 2022 at the Marrakech University Oncohematology Hospital. For each patient, we collected epidemiological, clinicopathological, therapeutic, and evolutionary data using an exploitation form. The age of the patients ranged from 27 to 95 years, with a peak between 61 and 70 years and a median of 64.32. Males predominated (74.6%). The matte skin phenotype was the most common, present in more than half of the patients. Among 63 patients surveyed, 69.8% had a history of prolonged sun exposure. Tumors of the head and neck were found in 65% of cases, with clinical appearance varying: 36.5% ulcerative-budding, 31.7% budding, 22.2% nodular, 6.4% sclerodermiform, and 3.2% ulcerated. Recurrences accounted for only 27% of consultations, and precancerous lesions were found in only 16% of patients. Most patients consulted at locally advanced stages (68.2%). Histologically, squamous cell carcinoma was confirmed in 63.5% of patients. External radiotherapy was performed in all patients, using three-dimensional conformal technique, adjuvant in 77.7% of cases, exclusive definitive in 19%, and palliative in 3.2% of cases. No patient received brachytherapy. Acute complications were observed in 52% of cases and late complications in 8%. After an average follow-up of 2 years, 76% of patients are still being followed in good disease control status with a complete response in 83% of them, 11% local recurrence, and 6% distant metastases. The incidence of cutaneous ........

Nonmelanoma facial skin cancer: surgical planning for resection and reconstruction

Introduction The most effective treatment for nonmelanotic fascial skin cancer is surgical excision. Preoperative planning and a thorough grasp of reconstructive procedures, such as primary closure skin grafting, locoregional tissue flaps, remote tissue flaps, and free tissue transfer, are essential for the surgical therapy of these tumors. The choice of nonmelanoma skin cancer (NMSC) therapy is very specific to each patient and is influenced by the patient’s age, size, histologic subtype, and location of the disease. Treatment is to obliterate the lesion while maintaining normal tissue, function, and appearance. The ideas and methods of surgical excision and reconstruction of skin malignancies unique to the face were covered in this study. Patients and methods This study involved 98 patients of various ages and sexes. Of them, 89% had basal cell carcinoma and 11% had squamous cell carcinoma, both low-and high-risk tumors with varying sizes, locations, and histological subtypes. A safety margin of 3–5 mm is used for excision of low-risk malignancies and 5–10 mm for high-risk cancers. In 17 patients, skin grafts (split-thickness skin grafts and full-thickness skin grafts) are employed. 56 patients underwent local advancement, transposition, and rotational flaps; 15 patients underwent regional interpolation flaps; 6 patients sustained neck lymph node infiltration so they underwent cervical block dissection and distant pedicled flaps as latissimus dorsi muscle flaps; and 4 patients underwent cervical block dissection and free tissue transfer. Results Six patients experienced problems in the form of two partial graft and flap losses, two wound infections, and one scar retraction; however, with targeted care, they recovered well. Ninety-two percent of patients found the cosmetic outcomes satisfactory, and the functional outcome was good. Conclusion Wide excision and appropriate surgical reconstruction are ideal treatment modalities and may yield good aesthetic results or functional outcome, also the use of split-thickness skin grafts does not come as a first priority, where a lot of cases could have been treated with local flaps, as demonstrated in this consecutive series of treated patients. Treatment of NMSC on the face required a basic knowledge, presents a challenge to plastic surgeons, and is based on achieving the best oncological, functional, and cosmetic result. It is crucial to emphasize the need of patient education and appropriate tumor monitoring after NMSC therapy. A review of a big series of facial malignancy that may guide further studies cannot be understated.

Image Guidance Improves Freedom From Recurrence Rate After Superficial Radiation Therapy for Nonmelanoma Skin Cancer

Image Guidance Improves Freedom From Recurrence Rate After Superficial Radiation Therapy for Nonmelanoma Skin Cancer

IMMUNOHISTOCHEMICAL ASSESSMENT OF PROLIFERATION AND APOPTOSIS OF KERATINOCYTES AFTER A SINGLE FRACTIONAL IONIZING IRRADIATION

Radiation therapy for non-melanoma skin cancers is used by oncologists and radiologists in cases of ineffective surgical treatment and as adjuvant or palliative therapy. The creation of experimental models to study the proliferative-apoptotic balance of keratinocytes makes it possible to assess the degree and depth of post-radiation skin damage after exposure to electrons in order to select optimal doses in the clinic. The purpose of the study: immunohistochemical assessment of proliferation and apoptosis of keratinocytes after local electron irradiation of the skin. The experiment used male Wistar rats (n=50), which were divided into groups: I – control (n=20), which were injected with saline solution, and experimental rats, which received local electron irradiation of the skin of the outer surface of the thigh: II – 8 Gy (n=10; single), III – 40 Gy (n=10, single), IV – fractional 13 Gy for 6 days with a total focal dose of 78 Gy (n=10;). After completion of the experiment, a skin biopsy of the outer surface of the thigh was performed and an immunohistochemical study of histological preparations with antibodies to the Ki-67, caspase-3 and p53 antigens was performed. Analysis of skin fragments after irradiation showed a shift in the proliferative-apoptotic balance towards keratinocyte apoptosis: a decrease in the level of Ki-67 expression and an increase in the number of p53-positive cells. After a single irradiation with electrons at doses of 8 Gy and 40 Gy, a significant increase in keratinocytes stained positively with antibodies to caspase-3 was found - by 3.4 and 6.6 times, respectively, and with a fractional irradiation mode at a total dose of 78 Gy - by 11.6 times compared to the control group. Thus, local irradiation with electrons in single doses of 8 Gy and 40 Gy leads to a shift in the proliferative-apoptotic balance of keratinocytes towards their apoptosis, the activity of which is directly proportional to the dose of ionizing radiation, and the fractional mode (total focal dose of 78 Gy) leads to partial desquamation of the epithelium and inflammatory infiltration.

Dilute Intralesional 5-Fluorouracil for the Treatment of Squamous Cell Carcinomas and Keratoacanthomas: A Case Series.

Intralesional 5-fluorouracil (5-FU) is a promising, yet sparsely studied alternative to surgical treatment for nonmelanoma skin cancer (NMSC).1 Previous studies of intralesional 5-FU have reported concentrations ranging from 30 to 50 mg/mL. To the best of our knowledge, this case series represents the first reported use of intralesional 5-FU 10.0 mg/mL and 16.7 mg/mL for NMSC. A retrospective chart review identified 11 patients who received intralesional 5-FU 10.0 mg/mL and 16.7 mg/mL for 40 cutaneous squamous cell carcinomas and 10 keratoacanthomas. We describe the characteristics of these patients and calculate the clinical clearance rate of dilute intralesional 5-FU therapy for NMSC at our institution. Dilute intralesional 5-FU successfully treated 96% (48/50) of the study lesions, providing complete clinical clearance in 82% (9/11) of patients across a mean follow-up time of 21.7 months. All patients tolerated their treatments well with no reported adverse effects or local recurrences. The use of more dilute preparations of intralesional 5-FU for NMSC may be a means of reducing cumulative dose and dose-dependent adverse reactions while maintaining clinical clearance. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.5058.

Ruthenium(ii) polypyridyl complexes with π-expansive ligands: synthesis and cubosome encapsulation for photodynamic therapy of non-melanoma skin cancer

Ru(ii) complexes featuring two π-expansive benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine ligands are potent photosensitizers that can be encapsulated into cubosomes to achieve hybrid formulations with augmented biopharmaceutical properties.

Superficial radiation therapy for nonmelanoma skin cancer: A review

AbstractBackgroundThe high prevalence of nonmelanoma skin cancer (NMSC) has become a global health‐care burden. Various modalities have been established to treat NMSC, with surgery being the mainstay approach. Superficial radiation therapy (SRT) has been in use for over a century to treat various conditions. Recent discussion among the dermatological community has promoted the use of SRT for the treatment of NMSC.Materials and MethodsA literature search was conducted using electronic databases (Medline, Pubmed, Embase, CINAHL, EBSCO) and textbooks, in addition to the authors' clinical experience with SRT.ResultsMultiple retrospective medical record reviews have deemed SRT to be highly effective and associated with minimal side effects. Moreover, SRT yields superior cosmetic results. Over the past decade, SRT has become a mainstay of dermatologist treatment of NMSC due to the new technological advances of the devices. These advances include improved controllability, precision in delivery, additional safety precautions, and have sparked a resurgence in research and clinical evidence on SRT. Most recent data have revealed that the NMSC cure rate is about 93%–100% with excellent 5‐year follow‐up data. Image‐guided SRT using ultrasound guidance may additionally improve cure rates in the future.ConclusionSRT has shown to be an effective option for NMSC. It can also be effectively used in the management of keloids. The limitations across most studies encompass localized patient selection and a predominance of retrospective reviews in the literature. Additional research is warranted to further support SRT's efficacy in clinical practice.

REDD1 interacts with AIF and regulates mitochondrial reactive oxygen species generation in the keratinocyte response to UVB

Non-melanoma skin cancer (NMSC) incidence is rising, especially in high-risk, immunocompromised groups such as organ transplant patients, who often develop numerous, aggressive cutaneous squamous cell carcinomas. Identifying the pathways that support NMSC development will result in new approaches for prevention and therapy. Our goal is to define the function of REDD1 (Regulated in DNA Damage and Development 1) in the UVB stress response. REDD1 is rapidly induced by a variety of stressors to repress mechanistic target of rapamycin complex I (mTORC1), and it has been reported that REDD1 loss causes dysfunctional mitochondria with increased reactive oxygen species (ROS) and impaired oxidative phosphorylation (OXPHOS). We now show that knockout of REDD1 in human keratinocytes sensitizes them to UVB-induced apoptosis in an mTORC1-independent manner and intensifies mitochondrial ROS generation. Upon REDD1 knockout, we observe reduced levels of apoptosis inducing factor (AIF), a mitochondrial intermembrane space NADH oxidase that is required for electron transport chain Complex I biogenesis. Further, we show that keratinocyte REDD1 interacts with both AIF and the mitochondrial import protein CHCHD4, a direct binding partner of AIF that ensures functional OXPHOS. Our results support the hypothesis that REDD1 is part of a mitochondrial complex that protects cells from UVB-induced ROS toxicity and suggest novel therapeutic targets for prevention and therapy of NMSC.

Passively Scattered Proton Therapy for Nonmelanoma Skin Cancer with Clinical Perineural Invasion

PurposeTo report our experience with the delivery of passively scattered proton therapy in the management of nonmelanoma skin cancers with clinical perineural invasion.Materials and MethodsWe reviewed the medical records of patients who received definitive or postoperative proton therapy for nonmelanoma skin cancer with clinical perineural invasion at our institution and updated patient follow-up when possible. All patients were treated with curative intent with or without the delivery of concurrent systemic therapy. We report disease control rates and the rates of late toxicity among this cohort.ResultsTwenty-six patients treated between 2008 and 2017 were included in the analysis. Following proton therapy, the 3-year overall, cause-specific, and disease-free survival rates were 59%, 73%, and 60%, respectively. The 3-year local control, local regional control, and distant metastasis-free survival rates were 80%, 65%, and 96%, respectively. On univariate analysis, surgical resection before radiation therapy significantly improved local regional control rates at 3 years (55% versus 86%; P = .04). Grade 3+ late toxicities occurred in 13 patients (50%) and the most common toxicities included grade 3+ keratitis of the ipsilateral eye, which occurred in 4 patients (15%) and grade 3+ brain necrosis in 4 patients (15%).ConclusionProton therapy is effective in the management of nonmelanoma skin cancer with clinical perineural invasion. Although disease control and complication rates compare favorably to those previously published for photon-based radiation therapy, the risk for late toxicity is significant and patients should be appropriately counseled.

Radiation therapy of non-melanoma skin cancer of the pinna: an Italian 35-year experience.

Radiation therapy (RT) is a well-known alternative to surgery for the treatment of non-melanoma skin cancer (NMSC), especially in elderly people or in patients who cannot undergo or refuse surgical procedure. It has also a pivotal role in those areas, as pinna, where both function and cosmesis must be preserved. We report our experience in treating cutaneous carcinoma of the auricle with radiation therapy. We conducted a retrospective monocentric study on 363 NMSC of the auricle treated by conventional energy radiation therapy as a primary treatment or with adjuvant and salvage purpose. Tumors involving the external canal of the ear or regional lymph node at diagnosis were excluded. A complete response has been obtained in 95.5% with a 2- and 5-year cure rate respectively of 84% and 76%. Fifty-two tumors developed a central or marginal relapse. Aesthetic result was good or acceptable in the majority of the cases. No cartilage necrosis has been registered. Our experience confirms safety and effectiveness of RT on selected auricle carcinoma, affording good cosmetic and functional results.

Forecasting and optimization of the kilovoltage X-ray therapy office within the framework of clinical guidelines of the Association of oncologists of Russia (AOR) of the Ministry of health of the Russian Federation

One of the elements of the quality of medical care is its accessibility, which depends on the material and technical baseof the institution, as well as on the availability of stuff and work management. Implementation of the new clinical guidelines of the Association of Oncologists of Russia (AOR) for the treatment of non-melanoma skin cancer (NRC), revealedthe problem of increasing the load on stuff and equipment.Purpose of the study.To investigate and forecast the load of the kilovoltage X-ray therapy unit taking into account theupdated clinical guidelines for the treatment of patients with non-melanoma skin cancer using radiotherapy. Determinethe clinical and organizational changes in the technology of x-ray therapy for non-melanoma skin cancer within theday-hospital department for the skin cancer size more than 2 cm after implementation of new clinical guidelines andfraction regimes in compare with previously used schemes; derive a mathematical model of the work of the kilovoltagex-ray therapy room.Materials and methods. Data from the kilovoltage X-ray therapy office of radiotherapy unit No. 2 of the Sverdlovsk Regional Oncology Dispensary (SROD) were used. The average duration of radiotherapy sessions per patient was estimatedand calculated using timekeeping. The results were evaluated using correlation analysis. In order to forecast the use ofmaterial and human resources, an economic method of mathematical modeling was used.Results. The analysis of the kilovoltage X-ray therapy unit of radiotherapy department No. 2 of the SROD for 3 yearsshowed an increase from 10.4 to 17.3 in the average number of therapeutic fractions per patient after the implementation of the updated clinical guidelines. An increase in the average number of radiotherapy sessions leads to a doublingof the average bed-day of the patient's stay in the day-hospital. The formula was proposed for predicting the work of theunit. There is a clear correlation between the duration of treatment, the dynamics of hospitalization and the number oftreated patients. The calculated results obtained using a mathematical model fully correspond to the actual performanceof the radiotherapy room.Conclusion. To ensure optimal availability of medical care, it is necessary to match treatment technologies with availableresources of the organization. The introduction of new treatment programs may require both the expansion of staff(medical, nursing), and an increase in the number of units of medical equipment. The obtained mathematical modelof the kilovoltage X-ray therapy room allows to predict the optimal mode of work of employees while maintaining thequality and accessability of medical care.

Near-Infrared Radiation-Based Mild Photohyperthermia Therapy of Non-Melanoma Skin Cancer with PEGylated Reduced Nanographene Oxide.

Using a one-step thermal reduction and non-covalent chemical functionalization process, PEGylated reduced nanographene oxide (rGOn-PEG) was produced from nanographene oxide (GOn) and characterized in terms of particle size, dispersion stability, chemistry, and photothermal properties, in view of its use for photothermal therapy (PTT) of non-melanoma skin cancer. GOn infrared spectrum presented more intense bands assigned to oxygen containing functional groups than observed for rGOn-PEG. GOn C/O ratio decreased more than 50% comparing with rGOn-PEG and nitrogen was present in the latter (N at % = 20.6) due to introduction of PEG-NH2. Thermogravimetric analysis allowed estimating the amount of PEG in rGOn-PEG to be of about 56.1%. Simultaneous reduction and PEGylation increased the lateral dimensions from 287 ± 139 nm to 521 ± 397 nm, as observed by transmission electron microscopy and dynamic light scattering. rGOn-PEG exhibited ≈13-fold higher absorbance in the near-infrared radiation (NIR) region, as compared to unmodified GOn. Low power (150 mW cm−2) NIR irradiation using LEDs resulted in rGOn-PEG heating up to 47 °C, which is within the mild PTT temperature range. PEGylation strongly enhanced the dispersibility of rGOn in physiological media (phosphate buffered saline, fetal bovine serum, and cell culture medium) and also improved the biocompatibility of rGOn-PEG, in comparison to GOn (25–250 μg mL−1). After a single NIR LED irradiation treatment of 30 min, a decrease of ≈38% in A-431 cells viability was observed for rGOn-PEG (250 μg mL−1). Together, our results demonstrate the potential of irradiating rGOn-PEG using lower energy, cheaper, smaller, and safer LEDs, as alternative to high power lasers, for NIR mild hyperthermia therapy of cancer, namely non-melanoma skin cancer.

Updates and new perspectives in nonmelanoma skin cancer therapy: highlights from 'Immunotherapy Bridge'.

Over the last few years, extensive research has improved our understanding of tumor immunology and has enabled the development of novel treatments. The state of the art of immunotherapy in various types of malignancies was exhaustively discussed in the 'Immunotherapy Bridge' meeting, which was held in Naples on 4-5 December 2019. Highlights related to the immunological treatment of nonmelanoma skin cancer are the content of this article.

Four－fraction radiation therapy for non－melanoma skin cancer

【目的】皮膚癌に対して短期間での根治治療を目的として行った4分割放射線治療について報告する。

Inhibition of mTORC2 enhances UVB-induced apoptosis in keratinocytes through a mechanism dependent on the FOXO3a transcriptional target NOXA but independent of TRAIL

The primary cause of non-melanoma skin cancer (NMSC) is ultraviolet B (UVB) radiation. We have shown previously that mTORC2 inhibition sensitizes keratinocytes to UVB-induced apoptosis mediated by the transcription factor FOXO3a. FOXO3a is a key regulator of apoptosis and a tumor suppressor in several cancer types. Activation of FOXO3a promotes apoptosis through the coordinated expression of a variety of target genes, including TRAIL and NOXA. We hypothesized that in the setting of mTORC2 inhibition, the UVB-induced expression of these factors would lead to apoptosis in a FOXO3a-dependent manner. Using spontaneously immortalized human keratinocytes (HaCaT cells), we observed that both TRAIL and NOXA expression increased in cells exposed to UVB and the TOR kinase inhibitor Torin 2. Similar to knockdown of FOXO3a, NOXA knockdown reversed the sensitization to UVB-induced apoptosis caused by mTORC2 inhibition. In contrast, loss of TRAIL by either knockdown or knockout actually enhanced expression of nuclear FOXO3a, which maintained apoptosis. These surprising results are not due to faulty death receptor signaling in HaCaT cells, as we found that the cells undergo extrinsic apoptosis in response to treatment with recombinant TRAIL. Even more striking, TRAIL knockout cells were sensitized to recombinant TRAIL-induced apoptosis compared to wild-type HaCaT cells, with the largest increase occurring in the presence of mTORC2 inhibition. Taken together, these studies provide strong evidence that mTORC2 controls UVB-induced apoptosis by regulating NOXA expression downstream of FOXO3a. Moreover, FOXO3a transcriptional activation by mTORC2 inhibitors may be a valuable target for prevention or therapy of NMSC, especially in cases with low endogenous TRAIL.

Mohs Micrographic Surgery for Treatment of Non-melanoma Skin Cancer

The aims of this report are to review literature supporting the use of Mohs micrographic surgery for treatment of non-melanoma skin cancer and to address indications and potential limitations of this form of therapy for non-melanoma skin cancer. The first randomized controlled trial comparing standard excision to Mohs micrographic surgery for treatment of facial basal cell carcinoma has recently been published, demonstrating a lower recurrence rate after Mohs surgery compared to standard excision after a 5-year and 10-year follow-up period, supporting its use in the treatment of high-risk basal cell skin cancer. Mohs micrographic surgery is indicated for treatment of basal cell carcinomas and cutaneous squamous cell carcinomas at high risk of recurrence and for tumors located in areas where tissue conservation and/or functional preservation is desired.

A synthesis of the world's guidelines on photodynamic therapy for non-melanoma skin cancer.

Photodynamic therapy (PDT), using topically administered photosensitizing agents, is widely approved as a treatment for certain nonmelanoma skin cancers. As a tissue-sparing non-surgical modality, there is great potential for PDT to enhance the choice of therapies available to treat, and potentially prevent, skin cancer. Treatment-specific guidelines have assessed the evidence for various photosensitizing agents and light sources, dosimetry, and evaluate reported adverse effects. Discomfort is frequently experienced during treatment but no analgesia was required in most pivotal lesion-directed studies. Durability of response has been assessed with studies of PDT for basal cell carcinomas (BCC) extending to 5 years and beyond, 2 years for Bowen's disease and up to 1 year for actinic keratoses (AK). Disease-specific guidelines consider the place for topical PDT in routine clinical practice recognizing that PDT is typically office/clinic-based and usually initiated by specialists. Where updated guidelines are awaited, national and international consensus publications offer recommendations, including on the use of daylight to activate the photosensitizer for treating AK. Reviewed studies indicate equivalent efficacy of daylight PDT, but greatly reduced pain compared with conventional PDT. Guidelines and consensus publications also consider the place of PDT in treating skin lesions arising in organ transplant recipients and in the potential for PDT to delay/prevent the development of nonmelanoma skin cancers. There is now a substantial evidence-base to support the use of topical PDT in routine clinical practice with daylight PDT indicated for AK, providing suitable outside climate, whilst conventional PDT remains suitable for AK, Bowen's Disease, superficial and certain thin nodular BCC.

Proton Therapy for Nonmelanoma Skin Cancers With Clinical Perineural Invasion

Proton Therapy for Nonmelanoma Skin Cancers With Clinical Perineural Invasion

Abstract 123: A novel J-series prostamide mediates D-series prostamide-induced apoptosis in skin cancer: receptor-independent signaling

Abstract Non-melanoma skin cancer (NMSC) is the most common cancer in the United States. The absence of selective toxicity is a major problem that limits the utility of chemotherapeutic and radiation therapy for NMSCs. Our previous data showed that the endocannabinoid, anandamide, selectively induced apoptosis in non-melanoma skin cancer (NMSC) cells which overexpress cyclooxygenase-2. The cytotoxic effect of anandamide was mediated by the production of ethanolamide-conjugated D- and J-series prostaglandins (PGs), also known as prostamide D2 (PMD2) and prostamide J2 (PMJ2), respectively. The aim of the current study was to determine if tumorigenic keratinocytes are more sensitive to PMD2 than non-tumorigenic cells and to examine whether the cytotoxicity of PMD2 is mediated by its downstream metabolite PMJ2. To determine if PMD2 demonstrates preferential toxicity, tumorigenic (JWF2) and non-tumorigenic (HaCaT) keratinocytes were utilized. A significant reduction in cell viability was observed in JWF2 but not in HaCaT cells treated with PMD2. In tumorigenic keratinocytes, PMD2 induced apoptotic cell death, oxidative stress and increased the expression of apoptotic ER stress protein, C/EBP homologous protein-10 (CHOP10). In addition, use of the antioxidant, trolox, and ER stress inhibitor, salubrinal, inhibited the cytotoxic effect of PMD2. Furthermore, the use of prostaglandin D receptor (DP1 and DP2) antagonists did not inhibit PMD2-induced apoptosis indicating that the activity was mediated by a receptor-independent pathway. Similar effects were observed in keratinocytes treated with the structurally-related arachidonic acid metabolite, prostaglandin D2 (PGD2). Interestingly, PMD2 increased the production of J-series prostaglandins in both tumorigenic and non-tumorigenic keratinocytes. LC-ESI-MS/MS analysis detected ethanolamide- conjugated J series PG (15-deoxy, Δ12,14 prostamide J2, 15d-PMJ2) in PMD2-treated cell culture media. Since selective inhibitors of the J-series prostaglandins are not available, 15d-PMJ2 was synthesized to examine its direct activity. Exogenous 15d-PMJ2 mimicked the activity of PMD2 demonstrating preferential cytotoxicity towards tumorigenic compared to non-tumorigenic keratinocytes. In addition, 15d-PMJ2 induced oxidative stress, ER stress and apoptosis in tumorigenic keratinocytes. These findings suggest that the cytotoxicity of PMD2 is mediated by 15dPMJ2. Since PMD2 and its metabolite 15d-PMJ2 are preferentially toxic towards tumorigenic cells, PMD2 or 15d-PMJ2 may be an ideal topical treatment for NMSC that will elicit minimal toxicity in healthy surrounding skin cells. Citation Format: Eman Soliman, Daniel Ladin, Hussam Albassam, Ahmed E. Elhassanny, Andrew Morris, Allison Danell, Rukiyah Van Dross. A novel J-series prostamide mediates D-series prostamide-induced apoptosis in skin cancer: receptor-independent signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 123. doi:10.1158/1538-7445.AM2017-123

Oral therapy for nonmelanoma skin cancer in patients with advanced disease and large tumor burden: a review of the literature with focus on a new generation of targeted therapies.

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.