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: Supportive Care in Cancer - Category: Cancer & Oncology Source Type: research
AbstractMultiple myeloma (MM) is diagnosed and monitored by correlating panel of test results including serum Protein electrophoresis (SPE), Immunofixation electrophoresis (IFE), serum Free Light chain (sFLC) measurements. This audit is aimed to evaluate the prevalence of non-correlation and discrepancies amongst the three investigations (SPE/IFE/sFLC) for assessment of MM. 106 MM patients were reviewed over 16  months in a tertiary cancer care center by the availability of 3 serum test results (SPE/IFE/sFLC). Patients were divided into 2 groups: group1, newly diagnosed MM patients who were yet to receive myeloma spec...
Source: Indian Journal of Clinical Biochemistry - Category: Biochemistry Source Type: research
CONCLUSIONS: LenMT dose correlated with efficacy and toxicity. High rates of dose reductions during CT argue against a high starting dose. However, continuous up- and down-titration for each patient to the current maximum tolerated dose is prudent. PMID: 32817078 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Conclusions: Patients with mm could benefit from a consistent tst testing policy coupled with subsequent ltbi therapy. However, universal testing might not be required. A targeted program combining evaluation of host risk factors, imaging findings, and screening tests might optimize ltbi diagnosis and management, and thus be effective in preventing the development of active tb in at-risk patients with mm. PMID: 32669929 [PubMed - in process]
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Conclusion: These results showed 212Pb-daratumumab to have efficacy in xenografted mice, with significant tumor regression and increased survival. This study highlights the potency of α-RIT in MM treatment.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Source Type: research
Chandran K Nair, Vineetha Raghavan, Atanu Bhattacharjee, Anju R KurupJournal of Cancer Research and Therapeutics 2020 16(1):88-93 Introduction: The impact of rapid reduction in paraprotein levels, with induction chemotherapy in myeloma, on treatment outcomes is less clear. There are very few studies in transplant ineligible patients treated with novel agents, correlating an early reduction in paraprotein with survival duration. Methods: In this retrospective analysis of newly diagnosed multiple myeloma, ineligible for stem cell transplant, paraprotein levels at baseline and 3 months were noted with percentage reduction. ...
Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
High-dose (HD) chemotherapy followed by autologous blood stem-cell transplantation (ASCT) is the standard treatment for multiple myeloma (MM) patients. However, the collection of sufficient peripheral blood st...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
tis The power of immunotherapy in the battle of Multiple Myeloma (MM) started with allogeneic stem cell transplantation, and was rediscovered with immunomodulatory drugs and extended with the outstanding results achieved with targeted antibodies. Today, next to powerful antibodies Elotuzumab and Daratumumab, several T-cell-based immunotherapeutic approaches, such as bispecific antibodies and chimeric antigen receptor-transduced T-cells (CAR T-cells) are making their successful entry in the immunotherapy arena with highly promising results in clinical trials. Nonetheless, similar to what is observed in chemotherapy, MM ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Conclusions: Our data show that baseline GPS correlates with rates of relapse and refractory disease in MM patients undergoing autologous transplantation. In a multivariate analysis, these effects were proven to hold prognostic capabilities beyond and independent from established prognosticators. These results require further validation in a prospective setting.
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
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