Antiangiogenic and antiapoptotic treatment in advanced melanoma

Melanoma is one of the most aggressive forms of skin cancer. Currently available treatments have little overall impact on survival rates of patients with advanced melanoma. Advances in the understanding of the molecular pathways related to tumor growth and metastatic spread have resulted in the development of targeted therapies designed to act on specific genes or molecules of these pathways. Newly introduced agents that target the process of angiogenesis or inhibit antiapoptotic proteins have been investigated in melanoma. Although the use of these agents as monotherapy has yielded disappointing results, their impact on survival when combined with cytotoxic chemotherapy agents is currently under investigation. Larger phase III trials are needed to clarify the optimal clinical benefit that can be expected of this class of agents. (C) 2013 Elsevier Inc. All rights reserved

Evolving Treatment Landscape of <i>HER2</i>-mutant Non-Small Cell Lung Cancer: Trastuzumab Deruxtecan and Beyond

Successful targeting of HER2-activating mutations in DESTINY-Lung02 phase II study has led to the approval of the antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) as second-line treatment in patients with non-small cell lung cancer (NSCLC). Despite the impressive results, several matters need to be addressed, including the clinical activity of T-DXd in patients with disease in the central nervous system as well as the role of T-DXd in the context of HER2 overexpression. Additionally, data regarding novel agents used to target HER2 continue to accumulate. This review highlights the challenges and unanswered questions that have emerged after the approval of T-DXd in patients with HER2-mutant NSCLC

Somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor and tyrosine kinase inhibitor response to TKIs in non-small cell lung cancer: An analytical database

Background: After the discovery of somatic mutations in the tyrosine kinase domain (exons 18-24) of the epidermal growth factor receptor (EGFR) correlating with responses of non-srnall cell lung cancer (NSCLC) to the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, there has been increasing interest in utilizing this molecular marker for treatment selection. We aimed to analytically catalogue the Mutational spectrum of somatic Mutations in EGFR and format a database allowing correlation of specific mutations with clinico-pathologic factors and response to TKIs. Methods: A computerized search of MEDLINE (January I 2004 to,June 30, 2007) was performed to identify articles reporting on NSCLC patients harboring somatic mutations in EGFR. Demographic, clinico-pathologic, Mutational, and response data were extracted and tabulated. Results: A total of 202 eligible articles were identified. We report data on 12,244 patients with 3381 somatic EGFR mutations. The majority Of mutations have been reported on only one occasion (158 of 254, 62.2%), and only nine Mutations occur at a rate of L858R and delE746-A750 account for 32.84% and 24.28% of all mutations, respectively; with 50% of mutations being exon 19 deletions or “deletional-insertions.” There is a clear association between the presence of Mutations and response to TKI. Conclusions: We have generated a free access, nonprofit online analytical database of somatic EGFR mutations in NSCLC. Cumulative information will be made available through a routine update of both database tables and associated graphical representations. Direct updates and Submissions through the online site (www.somaticmutations-EGFR.org) are encouraged, as are comments and suggestions

Therapeutic Effect of mRNA SARS-CoV-2 Vaccine on Melanoma Skin Metastases

A unique case of multiple metastatic melanoma skin nodules regression in a heavily pretreated, 72-year-old Caucasian female, after administering the second dose of the SARS-CoV-2 mRNA Pfizer-BioNTech vaccine, is presented. Two days after vaccination, all her melanoma skin nodules became painful and were significantly reduced in size. Physical examination and ultrasound imaging confirmed the patient’s observation. The effect was sustained, and further reduction of the nodules occurred after the third vaccine dose. One of the reduced nodules was removed, histologically examined, and its histopathology was compared to that of another such nodule removed and examined earlier. Distinct differences were observed between the two histopathologies, with the most notable the unexpected finding of the absence of infiltrating lymphocytes in the reducer nodule’s melanoma tissue. Based on this observation, the possible immunological mechanism(s) leading to the vaccine’s effect are speculated. More possible is the vaccine’s antitumor and apoptotic activity via stimulation of the Tol Like Receptors 3, 7, and 8, and (downstream) the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway of the non-lymphocytic immune effector cells