• Why multiple myeloma returns

    From ScienceDaily@1:317/3 to All on Tue Mar 1 21:30:38 2022
    Why multiple myeloma returns
    State-of-the-art protein analyses reveal new treatment target for bone
    marrow cancer

    Date:
    March 1, 2022
    Source:
    Charite' - Universita"tsmedizin Berlin
    Summary:
    Multiple myeloma, the most common type of bone marrow cancer
    in Germany, almost always returns, even after initial treatment
    success. In the majority of cases, the reasons behind this treatment
    resistance (e.g., genetic mutations) and the subsequent return of
    the disease, remain unknown. According to new research, it is the
    increased production of a specific protein which diminishes the
    cancer's sensitivity to treatment.



    FULL STORY ========================================================================== Multiple myeloma is a cancer which affects 'plasma cells', a type
    of immune cell found in the bone marrow. This cancer can weaken the
    immune system, cause kidney damage, and weaken bones, which may lead to fractures. Average survival rates have improved considerably thanks to
    new treatment options. These include lenalidomide and pomalidomide, drugs
    which are often successful in forcing the cancer into remission. In nearly
    all cases, however, the cancer will become increasingly less susceptible
    to these drugs, meaning it develops drug resistance. When cancer growth eventually resumes despite treatment, the patient's prognosis is poor.


    ========================================================================== Using latest improvements for a method known as proteomics, an interdisciplinary team of researchers in Berlin was able to decode a
    previously unknown mechanism which can cause this type of relapse. "We
    were able to show that production of CDK6, a cell division-promoting cell
    cycle regulator, is particularly high once the cancer has become resistant
    to treatment," explains one of the study's two co-leads, Prof. Dr. Jan
    Kro"nke of the Department of Hematology, Oncology and Cancer Immunology
    on Campus Benjamin Franklin. "Based on our data, we believe that CDK6 inhibition could represent a new treatment approach in relapsed multiple myeloma." Despite extensive DNA sequencing studies, treatment resistance
    in multiple myeloma has only rarely been linked to changes at the genetic level, such as gene mutations or gene deletions. "This suggests that
    the changes taking place within the cancer cell which would explain this relapse must take place at a different level," says the study's second
    co-lead, Dr. Philipp Mertins, an MDC researcher who heads the Proteomics Platform at both the MDC and the BIH. He continues: "The cancer cells'
    growth potential may also be subject to various means of control at the
    protein level. Here, we observed this type of effect in relation to the
    protein CDK6." The researchers employed cutting-edge mass spectrometry technology in order to establish whether changes at the protein level
    are responsible for the cancer becoming resistant to treatment. Using
    both pre- and post-relapse samples from patients with multiple myeloma,
    the researchers were able to quantify more than 6,000 different proteins.

    Comparing cancer cells collected before and after relapse, the researchers found that a range of proteins were present at either higher or lower concentrations post-relapse. Using statistical and bioninformatics
    analyses, the researchers were able to trace the majority of these
    effects back to a single protein: cyclin-dependent kinase 6, or CDK6,
    an enzyme which controls the cell's entry into the cell division phase
    of the cell cycle.

    As a first step, the researchers used cell cultures to demonstrate that
    CDK6 plays a key role in the development of treatment resistance in
    multiple myeloma. "When we artificially increased the amount of CDK6
    present inside cultured myeloma cells, they lost their susceptibility
    to the drugs lenalidomide and pomalidomide," explains the study's first
    author, Dora Ng, a researcher at the Department of Hematology, Oncology
    and Cancer Immunology on Campus Benjamin Franklin. She adds: "However,
    when we also added a CDK6 inhibitor, the drugs became effective again
    and the cancer cells died. This shows that CDK6 inhibition enables at
    least a partial reversal of the myeloma cells' treatment resistance."
    The researchers were then able to confirm this effect in an animal model,
    where the combination of pomalidomide with a CDK6 inhibitor significantly improved the odds of survival. "These data suggest that patients with treatment- resistant multiple myeloma may also benefit from the addition
    of CDK6 inhibitors," says Prof. Kro"nke, a researcher at the German
    Cancer Consortium's (DKTK) translational research center in Berlin, who
    is being funded via the DFG's Emmy Noether Program. "Further studies will
    be needed in order to test this hypothesis. One advantage is that some
    CDK6 inhibitors have already been authorized for use in the treatment of
    breast cancer." The study's second first author, Dr. Evelyn Ramberger,
    was responsible for performing the project's protein analyses. A postdoc
    at Charite' and the MDC/ BIH Proteomics Platform, she is convinced
    that the technology holds enormous benefits for the field of cancer
    research: "We want to continue pursuing this new approach of using modern, comprehensive protein analyses to study cancer tissues -- both in multiple myeloma and other cancers. We hope this will unveil further treatment
    targets and biomarkers for use in personalized cancer medicine," she says.

    ========================================================================== Story Source: Materials provided by
    Charite'_-_Universita"tsmedizin_Berlin. Note: Content may be edited for
    style and length.


    ========================================================================== Journal Reference:
    1. Yuen Lam Dora Ng, Evelyn Ramberger, Stephan R. Bohl, Anna Dolnik,
    Christian Steinebach, Theresia Conrad, Sina Mu"ller, Oliver Popp,
    Miriam Kull, Mohamed Haji, Michael Gu"tschow, Hartmut Do"hner,
    Wolfgang Walther, Ulrich Keller, Lars Bullinger, Philipp Mertins,
    Jan Kro"nke. Proteomic profiling reveals CDK6 upregulation
    as a targetable resistance mechanism for lenalidomide in
    multiple myeloma. Nature Communications, 2022; 13 (1) DOI:
    10.1038/s41467-022-28515-1 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220301131117.htm

    --- up 1 day, 10 hours, 50 minutes
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)