Malaria drug brings new hope for glioblastoma patients

Malaria drug brings new hope for glioblastoma patients

4794 3196 Anna Stelling, PhD

Glioblastoma is a very aggressive form of cancer. Even though there is a low number of patients who live longer than 5 years after diagnosis – a statistic that researchers are currently trying to understand – the majority of patients have a life expectancy between 12 and 15 months after the time of diagnosis.1 Glioblastoma multiforme (GBM) is a particularly aggressive form that lacks effective therapy options. Patients frequently acquire resistance to the current standard of care (SOC) treatment, which is radiation combined with the chemotherapeutic agent temozolomide (TMZ). And though recurrence is also frequent, there may still be hope.2 Yetirajam Rajesh (School of Medical Science and Technology, Indian Institute of Technology, India and Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, USA) and his team recently published a study showing that an anti-malaria drug can reverse acquired resistances – but how?2

Anti-malaria drug found to inhibit oncogenic protein

The upregulation of heat shock proteins (HSPs) was previously found to play a major role in GBM development and in the mechanism of resistance to radiation and TMZ treatment. This role can be attributed to their ability to regulate extracellular matrix (ECM) composition, as well as epithelial-mesenchymal transition (EMT).3 Dr Rajesh’s team found that the most upregulated HSP, HSPB1, is transcriptionally regulated by the Friend leukaemia integration (Fli-1) signalling network.2,4 This link animated the researchers to formulate their further hypothesis: inhibition of Fli-1 could have anti‑tumoural effects in GBM. To that end, the team initiated a screening for potential Fli-1 inhibitors. Their finding was a big surprise – lumefantrine, an FDA-approved anti-malaria drug, appeared to be a potent Fli-1 inhibitor.2

Induction of apoptosis in resistant GBM

Continuing their research with their newly found Fli-1 inhibitor, the researchers found that lumefantrine was able to suppress tumour growth and induce apoptosis in both non-resistant and resistant GMB cell lines. The same effects were observed in vivo. Resistant and non-resistant GMB cells were transplanted into the brains of mice and treated with lumefantrine. And indeed, the treatment also proved to be effective in this model, leading to a significant induction of apoptosis and growth suppression.2

The next steps – repurposing an approved drug

The finding was unexpected, yet opens possibilities of changing treatment options for patients with glioblastoma in the future. The researchers point out that lumefantrine could be “easily repurposed for management of GBM”, as it is already approved by the FDA. 2 Dr Rajesh also stresses that researchers should generally look more into the vast amount of available and approved drugs to find new opportunities for patients. Though Dr Rajesh and his team took the first step towards a new treatment, future research is still warranted to confirm its possible implications for patients with glioblastoma.


References
  1. Alexander BM, Cloughesy TF. J Clin Oncol. 2017;35:2402–9
  2. Rajesh Y et al. Proc Natl Acad Sci USA. 2020;117:12324–31
  3. Rajesh Y et al. Exp Cell Res. 2017;359:299–311
  4. Rajesh Y et al. Oncotarget. 2020;11:1097–108
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