The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma

• Published in: International journal of molecular sciences Vol. 25; no. 13; p. 6991
• Main Authors: Malamos, Panagiotis, Papanikolaou, Christina, Gavriatopoulou, Maria, Dimopoulos, Meletios A, Terpos, Evangelos, Souliotis, Vassilis L
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.06.2024
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Cell cycle; combination therapy; DDR/MAPK interplay; Disease; DNA Damage; DNA damage response (DDR); DNA Repair; Drug dosages; Drug resistance; Gene expression; Genomes; Humans; Kinases; MAP Kinase Signaling System; Medical prognosis; Medical research; mitogen-activated protein kinase (MAPK); Mitogen-Activated Protein Kinases - metabolism; Multiple myeloma; multiple myeloma (MM); Multiple Myeloma - genetics; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Plasma; Proteins; Signal transduction; Stem cell transplantation; mitogen-activated protein kinase (MAPK); combination therapy; DDR/MAPK interplay; multiple myeloma (MM); DNA damage response (DDR)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25136991

The DNA damage response (DDR) network and the mitogen-activated protein kinase (MAPK) signaling pathway are crucial mechanisms for the survival of all living beings. An accumulating body of evidence suggests that there is crosstalk between these two systems, thus favoring the appropriate functioning of multi-cellular organisms. On the other hand, aberrations within these mechanisms are thought to play a vital role in the onset and progression of several diseases, including cancer, as well as in the emergence of drug resistance. Here, we provide an overview of the current knowledge regarding alterations in the DDR machinery and the MAPK signaling pathway as well as abnormalities in the DDR/MAPK functional crosstalk in multiple myeloma, the second most common hematologic malignancy. We also present the latest advances in the development of anti-myeloma drugs targeting crucial DDR- and MAPK-associated molecular components. These data could potentially be exploited to discover new therapeutic targets and effective biomarkers as well as for the design of novel clinical trials. Interestingly, they might provide a new approach to increase the efficacy of anti-myeloma therapy by combining drugs targeting the DDR network and the MAPK signaling pathway.