gdc-0449 and Carcinoma

A wide range of treatments is now available for nonmelanoma skin cancer, including 5-fluorouracil, ingenol mebutate, imiquimod, diclofenac, photodynamic therapy, methotrexate, cetuximab, vismodegib, and radiotherapy. All are associated with high clinical and histologic response rates. However, some tumors do not respond due to resistance, which may be primary or acquired. Study of the resistance processes is a broad area of research that aims to increase our understanding of the nature of each tumor and the biologic features that make it resistant, as well as to facilitate the design of new therapies directed against these tumors. In this second article, having covered the topical treatments of nonmelanoma skin cancer, we review resistance to other nonsurgical treatments, such as monoclonal antibodies against basal and squamous cell carcinomas, intralesional chemotherapy, photodynamic therapy, and radiotherapy.

Topics: Anilides; Antigen-Presenting Cells; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma; Cetuximab; Clinical Trials as Topic; Combined Modality Therapy; Drug Resistance, Neoplasm; ErbB Receptors; Humans; Injections, Intralesional; Keratoacanthoma; Meta-Analysis as Topic; Methotrexate; Neoplasm Proteins; Neoplastic Stem Cells; Patched-1 Receptor; Photochemotherapy; Photosensitizing Agents; Pyridines; Radiation Tolerance; 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

The aim of this study was to describe the disease and treatment and to alert health professionals for the identification of signs and symptoms and the need for an early diagnosis in patients with xeroderma pigmentosum (XP).. An 8-year-old male patient was referred to the Joana de Gusmão Hospital (HIJG) in 2021 for evaluation and specialized care. Previously, the child was followed in his place of origin by oncologic and palliative care, where he was submitted to surgeries and chemotherapy. He was admitted to the HIJG using vismodegib, acitrein, tramadol, and solar protective measures. On physical examination, there were tumors and disseminated macular verrucous and ulcerated lesions. The imaging examination showed solid and expansive lesions on the face, and atelectasis and fibroscarring changes in the lung. The histopathological report proved the existence of melanocanthoma, carcinoma, and pyogenic granuloma. After the evaluation of the case, no surgery, chemotherapy, or radiotherapy was performed. It was decided to maintain the palliative treatment and to continue the use of tramadol for pain, and vismodegib and acitretin were used to control carcinomas and prophylactic measures.. The XP is a rare disease of autosomal recessive inheritance whose mechanism comes from failure in the DNA repair by exposure to ultraviolet rays, resulting in lesions on the skin and mucous membranes. They start as sunburns and can progress to melanosis, areas with altered pigmentation, premature aging, poikiloderma, and areas of high risk for neoplasms.

Topics: Carcinoma; Child; DNA Repair; Humans; Male; Skin Diseases; Skin Neoplasms; Tramadol; Xeroderma Pigmentosum

Given the gut microbiome's rise as a potential frontier in cancer pathogenesis and therapy, leveraging microbial analyses in the study of breast tumor progression and treatment could unveil novel interactions between commensal bacteria and disease outcomes. In breast cancer, the Hedgehog (Hh) signaling pathway is a potential target for treatment due to its aberrant activation leading to poorer prognoses and drug resistance. There are limited studies that have investigated the influences of orally administered cancer therapeutics, such as Vismodegib (a pharmacological, clinically used Hh inhibitor) on the gut microbiota. Using a 4T1 mammary carcinoma mouse model and 16 S rRNA sequencing, we longitudinally mapped alterations in immunomodulating gut microbes during mammary tumor development. Next, we identified changes in the abundance of commensal microbiota in response to Vismodegib treatment of 4T1 mammary tumor-bearing mice. In addition to remodeling gut microbiota, Vismodegib treatment elicited an increase in proliferative CD8

Topics: Animals; Carcinoma; CD8-Positive T-Lymphocytes; Disease Models, Animal; Gastrointestinal Microbiome; Hedgehog Proteins; Mice

Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

Topics: Adult; Anilides; Antineoplastic Agents; Carcinoma; Carcinoma, Basal Cell; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Multimodal Imaging; Neoplasm Invasiveness; Positron-Emission Tomography; Pyridines; Skin Neoplasms; Treatment Outcome