Cancers, Vol. 11, Pages 1779: Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia

Cancers, Vol. 11, Pages 1779: Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia Cancers doi: 10.3390/cancers11111779 Authors: Katja Seipel Karin Schmitter Ulrike Bacher Thomas Pabst Amplification and overexpression of the myeloid cell leukemia differentiation protein MCL1 and the murine double minute protein MDM2 have been reported in various human tumors as well as hematological malignancies including acute myeloid leukemia (AML). While MCL1 is an anti-apoptotic member of the BCL-2 family proteins, MDM2 is an important cellular inhibitor of the p53 tumor suppressor. The key oncogene in AML is the FLT3 growth factor receptor gene. FLT3 signaling pathways including the MAPK cascade (RAS-RAF-MEK-ERK) are highly active in AML cells, leading to induced protein translation and cell proliferation as well as reduced apoptosis. Consequently, combined administration of MCL1-, MDM2-, and MEK-inhibitors may present a promising anti-leukemic treatment strategy. Here, we assessed the MCL1-antagonist S63845, the MDM2-inhibitor HDM201, and the MEK1/2-inhibitor trametinib as single agents and in combination in a variety of AML cell lines and mononuclear cells isolated from patients with hematological malignancies centered on myeloid leukemia, some lymphatic leukemia, as well as some lymphomas, for their ability to induce apoptosis and cell death. We observed a considerably varying anti-leukemic efficacy of the MCL1-inhibitor S6...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

Related Links:

Publication date: October 2020Source: Clinical Lymphoma Myeloma and Leukemia, Volume 20, Issue 10Author(s): Prajwal Dhakal, Elizabeth Lyden, Kate-Lynn E. Muir, Zaid S. Al-Kadhimi, Lori J. Maness, Krishna Gundabolu, Vijaya Raj Bhatt
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
esco Albano Immunomodulatory drugs (IMiDs) are analogs of thalidomide. They have immunomodulatory, antiangiogenic and proapoptotic properties and exert a role in regulating the tumor microenvironment. Recently IMiDs have been investigated for their pleiotropic properties and their therapeutic applications in both solid tumors (melanoma, prostate carcinoma and differentiated thyroid cancer) and hematological malignancies. Nowadays, they are applied in de novo and relapsed/refractory multiple myeloma, in myelodysplastic syndrome, in del5q syndrome with specific use of lenalidomide and B-cell lymphoma. Several studies hav...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
CONCLUSIONS: There was no convincing evidence of an increased risk in any hematological malignancy when interpreting the results from both series of analyses. PMID: 32818321 [PubMed - as supplied by publisher]
Source: Transfusion - Category: Hematology Authors: Tags: Transfusion Source Type: research
Advanced Hodgkin lymphoma (HL) are treated with two different chemotherapy regimens (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine [ABVD] or bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, and prednisone [BEACOPP]) that have two different toxicity profiles. In this pooled analysis of four randomized trials comparing these two regimens, and with a median follow ‐up of 7 years, progression‐free survival is significantly superior with the BEACOPP regimen. The 7 years overall survival was 84.3% for ABVD and 87.7% for BEACOPP. The main caus...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
In conclusion, we identified AML methylation subtypes and their marker genes, these results may help to excavate potential targets for clinical therapy and the development of precision medicine for AML patients.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
We hypothesized that higher Charlson comorbidity index(CCI) predicts worse one-month mortality and overall survival(OS) in patients ≥60 years with acute myeloid leukemia(AML). In our National Cancer Database study, patients with CCI 0 were more likely to receive chemotherapy and undergo upfront hematopoietic cell transplant. One-month mortality and OS were significantly worse with CCI 1 or ≥2, compared to CCI 0.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research
By CHADI NABHAN, MD, MBA, FACP “The goal for me and for my clinical and research colleagues is to put ourselves out of a job as quickly as possible”. This is how Mikkael Sekeres ends his book “When Blood Breaks Down” based on true stories of patients with leukemia. I share Mikkael’s sentiments and have always stated that I’d be happy if I am out of a job caring for patients with cancer. To his and my disappointment, this wish is unlikely to ever come true, especially when dealing with leukemia. With almost 15 years of experience, Sekeres possesses a wealth of knowledge and pati...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: Medical Practice Physicians Book Review Chadi Nabhan hematology Mikkael Sekeres Oncology When Blood Breaks Down Source Type: blogs
We examined the outcomes of 818 adult patients with relapsed/refractory acute myeloid leukemia (R/R AML) treated at MD Anderson Cancer Center between 2002 –2016. Complete remission rates decreased from 14% after first salvage, to 9% after second salvage, and 3% after third salvage. Strategies that improve initial response and decrease the likelihood of relapse are needed to achieve long-term remission for AML.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research
CONCLUSION: The findings in this study provide evidence that DHODH inhibitors perturb the proliferation of non-cancerous cells via a distinct mechanism compared to cancerous cells. These results may lead to strategies for overcoming the impact on non-cancerous cells during treatment with DHODH inhibitors, leading to better therapeutic window in patients. PMID: 32525770 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research
Publication date: Available online 21 April 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Samah Fathy Semary, Mahmoud Hammad, Sonya Soliman, Dina Yassen, Marwa Gamal, Doaa Albeltagy, Nayera Hamdy, Sonia Mahmoud
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
More News: Acute Leukemia | Acute Myeloid Leukemia | Cancer | Cancer & Oncology | Genetics | Hematology | Leukemia | Lymphoma