China
Africa
Explore chapters and articles related to this topic
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Experimentally, sonidegib has also demonstrated significant efficacy in preclinical models of many other cancer types including solid (e.g., melanoma, pancreatic, breast, small-cell lung, medulloblastoma, ovarian, stomach, esophageal, and glioblastoma multiforme) and hematological (e.g., acute and chronic myeloid leukemias) cancers.
Targeted Therapy for Cancer Stem Cells
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Rama Krishna Nimmakayala, Saswati Karmakar, Garima Kaushik, Sanchita Rauth, Srikanth Barkeer, Saravanakumar Marimuthu, Moorthy P. Ponnusamy
HH signaling is an important pathway during embryogenesis and development that communicates the information to embryonic cells required for proper cell differentiation [55, 56]. The major molecules of HH signaling that regulate the activation and repression of this pathway are Sonic, Desert and Indian, their receptor Patched, transmembrane protein Smoothened (SMO), and three Gli transcription factors (Gli 1-3) [57]. Experimental studies on samples from mouse, patient, and cancer cell lines have shown the activation of abnormal HH signaling in CSCs of various cancers, including multiple myeloma, glioblastoma, colon cancer, chronic myeloid leukemia (CML), etc.[49]. HH signaling plays an essential role in epithelial to mesenchymal transformation (EMT); for example, knockdown of Gli resulted in decreased CSCs’ viability, motility, clonogenicity, and self-renewal in claudin-low breast CSCs [58]. As HH signaling plays a significant role in CSCs self-renewal and regulation, inhibiting HH signaling can thus interrupt CSCs stemness and induce their differentiation, which is desirable for cancer treatment. Researchers have developed numerous therapeutic agents for targeting the HH pathway. Vismodegib is the first FDA approved HH inhibitor developed by Genentech, which targets SMO and is used for the metastatic basal cell carcinoma treatment [59, 60]. At present, Vismodegib in clinical trials is used as monotherapy or in combination with other therapeutic agents to treat several cancers, such as metastatic pancreatic cancer, metastatic prostate cancer, recurrent glioblastoma, acute myeloid leukemia, small cell lung cancer and medulloblastoma [61]. Sonidegib is another FDA approved HH inhibitor in 2015, which also targets the SMO and is used for the treatment of adult patients with locally advanced BCC [62]. However, the drug has grade 1/2 adverse effects, comprising nausea, anorexia, vomiting, muscle spasms, fatigue and grade 3/4 adverse effects, such as weight loss, hyperbilirubinemia, myalgia and dizziness [62]. Several phase I/II trials of Sonidegib to treat other solid tumors and hematological malignancies are still underway [61]. Other inhibitors targeting the HH signaling that were tested in clinical trials include SMO inhibitors (BMS-833923, Glasdegib, and PF-5274857) and Gli inhibitor (arsenic trioxide). Along with these, a monoclonal antibody 5E1 which inhibits the binding of all three HH mammalian ligands to PTCH is also developed [63]. However, this antibody has not yet been entered in clinical trials.
Efficacy and safety of sonidegib for the management of basal cell carcinoma: a drug safety evaluation
Published in Expert Opinion on Drug Safety, 2023
Alessia Villani, Massimiliano Scalvenzi, Giuseppe Micali, Francesco Lacarrubba, Lucia Genco, Angelo Ruggiero, Luigi Fornaro, Gianluca Guerrasio, Luca Potestio
Skin cancers are increasing worldwide, leading to new treatment challenges [36–39]. Among these, BCC are the most common [40]. The goal of the management of these types of tumors should be the right therapeutic approach at the diagnosis, in order to avoid the evolution to laBCC or metastatic BCC [41]. Currently, many treatments are available based on the clinical features and patients’ characteristics [41]. Globally, the surgical treatment still remains the gold-standard for the majority of BCCs [41]. However, there are some forms of BCCs, the so-called ‘difficult-to-treat’ BCC, where surgery is not a therapeutic option [42]. The management of these forms of BCCs is challenging. Indeed, chemotherapy showed a low response rate and a low duration of response while the use of immunotherapy is currently under investigation [42,43]. In this scenario, new knowledge on the pathogenesis of BCC, particularly the HH-pathway, led to the development of new effective and oral drug [44,45]. Currently, two HH-inhibitors have been approved: vismodegib and sonidegib. Vismodegib has been used for longer time allowing the availability of several data in terms of effectiveness and safety deriving from clinical trials and real-life experiences [44–49]. On the contrary, despite data from clinical trials about the use of sonidegib are consistent [26–29], evidence from real-life are scant [30–35]. Thus, we investigated the efficacy and safety of sonidegib, in order to point out its strengths and limitations in daily clinical practice.
Emerging therapeutic options for periorbital and orbital cutaneous basal and squamous cell carcinomas
Published in Orbit, 2023
Edward J. Wladis, Stephen H. Wrzesinski, Michael I. Rothschild, Alejandro P. Adam
Based on reports that suggested that higher response rates may be achieved more rapidly with fewer side effects with sonidegib than with vismodegib,24 DeGiorgi et al. recommended a particular protocol for ocular adnexal basal cell carcinomas. Specifically, they recommended the use of 200 mg of oral sonidegib daily for four monthly cycles. If the patient experiences a complete response, sonidegib could be reduced to 200 mg daily for one week, followed by a three-week holiday until toxicity develops. However, if the four cycles resulted in a partial response with surgically resectable disease, the authors recommend surgery. In the presence of a partial response with disease that cannot be resected, the authors advise using 200 mg every other day and reassessing after three cycles.
Expert opinion on sonidegib efficacy, safety and tolerability
Published in Expert Opinion on Drug Safety, 2021
Alessia Villani, Gabriella Fabbrocini, Claudia Costa, Sonia Sofia Ocampo-Garza, Aimilios Lallas, Massimiliano Scalvenzi
The use of Hh inhibitors has been shown to be efficacious in reducing tumor size, in most cases up to complete remission [36]. Moreover, positive results have also been reported in the case of patients with NBCCS, as BCCs regression and absence of progression have been described in many patients. Sonidegib showed to be an effective and safe drug in elderly people with underlying medical conditions, such as multiple myeloma, despite the occurrence of related adverse events. Several AEs related to the drug and laboratory abnormalities, the majority being of grade 1–2 of severity, have been described [37,38]. AEs usually appear after a few weeks from the beginning of treatment, so patients must be informed and educated to better manage these AEs and regular follow-up visits are required in order to promptly treat them avoiding treatment discontinuation [39].