RAS Signaling Pathway in Cancer Therapy
A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".
Deadline for manuscript submissions: 16 August 2024 | Viewed by 5618
Special Issue Editor
Special Issue Information
Dear Colleagues,
Mutations in one of the RAS genes are found in a quarter of all human cancers. Since their discovery, researchers have attempted to develop therapeutic strategies to inhibit RAS oncoproteins, either directly or indirectly; however, it was not until 2021 that the first inhibitor that blocks one of the mutant isoforms of KRAS (KRASG12C) in its inactive state was finally approved. Moreover, other strategies are currently being developed, including those that inhibit this oncoprotein in its active form or approaches to target other mutant isoforms. Given that RAS signaling plays a critical role in several cellular activities such as cell proliferation, a deeper understanding of RAS signaling in cancer, but also in development or homeostasis, is urgently required to further improve the therapeutic options for patients with tumors harboring RAS mutations.
The scope of this Special Issue is to further advance our understanding of the unique requirements for RAS signaling in distinct contexts such as tumor initiation, growth, or maintenance. Genetic studies in particular, although not exclusively, have the potential to uncover novel vulnerabilities that may ultimately expand the therapeutic options for patients with acquired or even intrinsic resistance. More importantly, genetic studies can also provide knowledge regarding essential requirements for RAS signaling in more universal contexts, with the final goal being to keep the therapy-related toxicities as low as possible.
Dr. Matthias Drosten
Guest Editor
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
Keywords
- RAS signaling
- MAPK pathway
- RAS effectors
- KRAS inhibitors
- resistance
- drug combinations
- tumor growth mechanisms
- signaling pathways
- toxicity
Planned Papers
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: Preclinical therapeutic efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR inhibition in neuroblastoma
Authors: Stacey Stauffer; Jacob S. Roth; Edjay R. Hernandez; Joshua T. Kowalczyk; Nancy E. Sealover; Norris Lam; Katie E. Hebron; Xiaolin Wan; Amy James; Kristine A. Isanogle; Lisa A. Riffle; Lilia Ileva; Xiaoling Luo; Jin-Qiu Chen; Noemi Kedei; Robert L. Kortum; Haiyan Lei; Jack F. Shern; Joseph D. Kalen; Elijah F. Edmondson; Matthew D Hall; Simone Difilippantonio; Carol J. Thiele; Marielle E Yohe
Affiliation: National Cancer Institute
Abstract: Activating mutations in the RAS/MAPK pathway are observed in relapsed neuroblastoma. Pre-clinical studies indicate these tumors have an increased sensitivity to inhibitors of the RAS/MAPK pathway such as MEK inhibitors. MEK inhibitors do not induce durable responses as single agents, indicating a need to identify synergistic combinations of targeted agents to provide therapeutic benefit. We previously showed preclinical therapeutic synergy between a MEK inhibitor, trametinib, and a monoclonal antibody specific for IGF1R, ganitumab in RAS-mutated rhabdomyosarcoma. Neuroblastoma cells, like rhabdomyosarcoma cells, are sensitive to inhibition of the RAS/MAPK and IGF1R/AKT/mTOR pathways. We hypothesized that the com-bination of trametinib and ganitumab would be effective in RAS-mutated neuroblastoma. In this study, trametinib and ganitumab synergistically suppressed neuroblastoma cell proliferation and induced apoptosis in cell culture. We also observed a delay in tumor initiation and prolongation of survival in heterotopic and orthotopic xenograft models treated with trametinib and ganitumab. However, growth of both primary and metastatic tumors was observed in animals receiving the combination of trametinib and ganitumab. Therefore, more preclinical work is necessary before testing this combination in patients with relapsed or refractory RAS-mutated neuroblastoma.