Nat Chem Biol: Reveals the molecular structure of the effective treatment of multiple myeloma with the drug Pomadamine.

October 6, 2020 // -- Multiple myeloma is a type of leukocyte cancer that usually occurs within 5 years, and clinicians often use the drug thalidomide and its structurally similar drugs (e.g. To treat patients with multiple myeloma, the drug Pomadamine usually brings some therapeutic benefits to patients with multiple myelomas that are resistant to amines, but researchers do not yet know the specific molecular mechanisms behind it.
Photo Source: In a recent study published in the international journal Nature Chemical Biology, scientists from the Tokyo Institute of Technology and others revealed the molecular mechanisms behind the therapeutic benefits of the drug pomadamine, which they found triggers the breakdown of the ARID2 protein, which Promoting gene expression that is critical to the growth of multiple myeloma cells, so destroying ARID2 inhibits cancer cell growth and proliferation and can bring therapeutic benefits to patients. In this study, researchers revealed the molecular mechanisms by which Pomadamine works, and they also gained an in-depth understanding of the clinical importance of ARID2 and its associated proteins in the context of multiple myeloma.
To reveal how pomadamine affects multiple myeloma cells, scientists conducted a series of experiments on multiple myeloma cells in culture, which showed that the treatment of multiple myeloma cells with pomadamine may reduce ARID2 levels in cells, while high concentrations of pomadamine and long-term exposure time can continue to reduce ARID2 The level of ARID2 promotes the expression of the MYC gene, which is important for the growth of myeloma cells and reduces myC levels in cells with positamine when treating cells with lower ARID2 levels, and the paper also reveals how the use of pomatamin affects the levels of ARID2 and MYC in myeloma cells at different times.
The results of this paper may better explain why pomadamine is effective in helping to fight multiple myeloma, and interestingly, in reducing ARID2 levels and the expression of myc genes, amine may not be as effective as posamine, which may also explain why some patients benefit more from the treatment of pomadamine; Poor prognosis is directly related, and its level is higher in patients with recurring or resuscable multiple myeloma, and the higher level of expression of ARID2 in the patient's body means that the survival rate of patients with high levels of ARID2 is lower than in patients with lower levels of ARID2 expression, i.e. ARID2 may serve as a useful prognostic marker to help predict the overall survival of patients with multiple myeloma.
final researcher Yamamoto said the results of this paper may help explain the molecular mechanism by which pomadamine brings therapeutic benefits to patients with multiple myeloma who are resistant to amines, and could also help scientists design new ways to treat patients with multiple myeloma. The researchers believe that ARID2 may be a potential target to help overcome multiple myelomas that are resistant to amines, and later researchers will continue to delve into finding new ways to improve the therapeutic benefits and prognosis of patients with multiple fatal cancers.
() Original source: Yamamoto, J., Suwa, T., Murase, Y. et al. ARID2 is a pomalidomide-dependent CRL4CRBN substrate in multiple myeloma cells. Nat Chem Biol (2020).doi:10.1038/s41589-020-0645-3.