Cancers, Vol. 12, Pages 455: Exon-4 Mutations in KRAS Affect MEK/ERK and PI3K/AKT Signaling in Human Multiple Myeloma Cell Lines

Cancers, Vol. 12, Pages 455: Exon-4 Mutations in KRAS Affect MEK/ERK and PI3K/AKT Signaling in Human Multiple Myeloma Cell Lines Cancers doi: 10.3390/cancers12020455 Authors: Susann Weißbach Sofia Catalina Heredia-Guerrero Stefanie Barnsteiner Lukas Großhans Jochen Bodem Hanna Starz Christian Langer Silke Appenzeller Stefan Knop Torsten Steinbrunn Simone Rost Hermann Einsele Ralf Christian Bargou Andreas Rosenwald Thorsten Stühmer Ellen Leich Approximately 20% of multiple myeloma (MM) cases harbor a point mutation in KRAS. However, there is still no final consent on whether KRAS-mutations are associated with disease outcome. Specifically, no data exist on whether KRAS-mutations have an impact on survival of MM patients at diagnosis in the era of novel agents. Direct blockade of KRAS for therapeutic purposes is mostly impossible, but recently a mutation-specific covalent inhibitor targeting KRASp.G12C entered into clinical trials. However, other KRAS hotspot-mutations exist in MM patients, including the less common exon-4 mutations. For the current study, the coding regions of KRAS were deep-sequenced in 80 newly diagnosed MM patients, uniformely treated with three cycles of bortezomib plus dexamethasone and cyclophosphamide (VCD)-induction, followed by high-dose chemotherapy and autologous stem cell transplantation. Moreover, the functional impact of KRASp.G12A and the exon-4 mutations p.A146T and p.A146V on different sur...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, around 20% of all patients with HBV reactivation developed HBV reactivation after 2 years from the initiation of therapy, unlike malignant lymphoma. This might be due to the fact that almost all of the patients received chemotherapy for a long duration. Therefore, a new strategy for the prevention of HBV reactivation in MM patients is required.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
CONCLUSION: All tested biosimilars demonstrated similar effectiveness and safety profiles in patients with hematological tumors undergoing PBSC mobilization; therefore, they can be used interchangeably. PMID: 31663634 [PubMed - as supplied by publisher]
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: J Clin Apher Source Type: research
Patients with Multiple Myeloma (MM) are enjoying significant improvement in overall survival as the result of advent of novel anti-myeloma agent that replace traditional chemotherapy, in addition to the increased use of transplant. The prices of novel agents, especially oral ones, have been rapidly escalating and there are well-described issues with affordability (Shih et al. JCO 2017). We therefore hypothesized that insurance status influences MM patients (pts) survival. National Cancer Database (NCDB), covering 70% of MM patient nationwide was utilized.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Historically at Princess Margaret Cancer Centre, cyclophosphamide and GCSF was the standard stem cell mobilization regimen used for transplant eligible multiple myeloma patients. Limitations to this regimen included chemotherapy associated toxicity such as febrile neutropenia, and unpredictability regarding the ideal planned apheresis start date. With the recent validation of open-vial sterility of plerixafor allowing for broader access at our centre (Seki et al. Can J Hosp Pharm 2017;70:270), an opportunity was identified to transition to a less toxic GCSF alone mobilization regimen.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Treatment of multiple myeloma (MM) with induction chemotherapy followed by autologous hematopoietic cell transplant (auto HCT) improves event-free survival and overall survival. This prolonged survival has unmasked long-term complications related to therapy that impact quality of life. Studies in other cancers have identified cognitive impairment related to chemotherapy treatment based on exposure or dose. To date, there are no studies evaluating the impact auto HCT may have on cognition in MM patients.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Hui Zhou, Xiaoyan Fu, Qian Li and Ting Niu* Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clin...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion In this section, we discuss the mechanisms responsible for lymphomagenesis in the various inborn errors of immunity and provide an overview of the treatment. Defects in Immune Responses That Predispose to Lymphomagenesis in PIDDs The complex immune mechanisms and their interplay that predisposes to neoplastic transformation of B or T cells and development of lymphomas in PIDD patients has not been fully elucidated. However, it is expected that the etiology in most cases is multifactorial and related to a dynamic regulation of immune response and environmental triggers (Figure 3). An underlying intrinsic susce...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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