On the just occurred World Cancer Day, we had the opportunity to reflect on the growing body of research in cancer development, immune modulation, and drug resistance.
Several studies focus on HMGB1 protein particular influence in cancer. Under normal conditions, HMGB1 maintains genomic stability and supports cellular homeostasis. However, in the context of cancer, HMGB1 undergoes significant functional shifts, influencing tumor progression, immune evasion, and therapy response.
HMGB1 in NSCLC: a driver of malignancy and drug resistance
Lung cancer remains one of the most challenging malignancies to treat, and NSCLC accounts for nearly 85% of all cases. Despite advances in therapy, resistance to chemotherapy remains a major hurdle.
A research published on Springer Nature has established HMGB1 as a major contributor to the progression and chemoresistance of non-small cell lung cancer (NSCLC). Elevated HMGB1 expression is associated with increased tumor aggressiveness, higher levels of inflammatory mediators, and enhanced resistance to cisplatin-based chemotherapy.
- HMGB1 levels were significantly elevated in malignant pleural effusions (MPE) compared to benign pleural effusions (BPE), highlighting its potential for disease progression.
- Recurrent tumor tissues showed increased expression of HMGB1, drug-resistance proteins (such as P-glycoprotein), and anti-apoptotic markers, suggesting a role in tumor survival and adaptation.
- HMGB1 overexpression enhanced NSCLC cell proliferation, invasion, and resistance to cisplatin, while HMGB1 inhibition reversed these effects.
- HMGB1 localization correlated with drug resistance: In a xenograft model, high HMGB1 expression was found in the cytoplasm, co-localizing with drug-resistance proteins, whereas lower HMGB1 levels remained confined to the nucleus.
These findings reinforce HMGB1’s role in NSCLC progression and drug resistance,highlighting the need for targeted approaches to disrupt its tumor-promoting functions.
Given its involvement in these critical processes, HMGB1 represents an attractive therapeutic target. Potential strategies to counteract its tumor-promoting effects include: HMGB1 inhibitors to block its extracellular signaling and Targeting P-gp interactions to prevent chemotherapy resistance.
HMGBiotech Srl provides comprehensive information to facilitate informed decision-making for researches with HMGB1.
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Read the full article about the study:
https://hereditasjournal.biomedcentral.com/articles/10.1186/s41065-023-00294-9
