‘Repurposing’ malaria drug to treat castrate-resistant prostate cancer

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Kolkata: Tapping into the trend of repurposing old approved drugs to treat totally different diseases — a strategy that led to the development of Viagra, researchers at IIT-Kanpur have shown how a malaria drug can be used to tackle drug resistance in metastatic prostate cancer.

The procedure is targetted towards tackling resistance to anti-androgen drugs.

The team at the Molecular Oncology Lab of the Department of Biological Sciences and Bioengineering, Indian Institute of Technology – Kanpur, used the well-known malaria drug, Artesunate to restore sensitivity of prostate cancer cells to the medication Bicalutamide, an anti-androgen.

“This study for the first time provides a compelling pre-clinical rationale that Artesunate could disrupt androgen receptor antagonist or anti-androgen drugs-resistance observed in patients who don’t respond to Androgen Deprivation Therapy (ADT), and progress to metastatic castration-resistant prostate cancer (mCRPC),” Bushra Ateeq, Assistant Professor and Intermediate Fellow, Wellcome Trust-DBT India Alliance, at the IIT-Kanpur, told IANS.

Androgens (also considered as a steroid) such as testosterone are known to promote male characteristic traits and reproductive activity.

Prostate cancer cells also need androgen for their growth, in the early stages of the disease.

These types of prostate cancers are known as “androgen-dependent” or “androgen-sensitive”.

ADT (the first-line of treatment) works by starving these cancerous cells of androgen to inhibit their development, explained Ateeq.

Unfortunately, invariably most of these patients develop resistance (to ADT) and become mCPRC.

Metastatic prostate cancer is an aggressive stage that is treated with a range of hormonal therapies.

This stage is associated with a poor prognosis and on average the survival time for these patients is only 16-18 months, Ateeq said.

“It has been reported that prostate cancer among Indian men is usually of higher grade and more likely to be metastatic at diagnosis as compared to Western counterparts,” she said.

Artesunate, which is an FDA — and World Health Organization (WHO) — approved anti-malarial drug, derived from sweet wormwood (Artemisia annua), could be used to restore the sensitivity of the mCRPC condition to anti-androgens or ADT, she said.

“We for the first time have shown that the Artesunate in combination with Bicalutamide, could reduce cell proliferation, invasion and motility of the castrate-resistant prostate cancer cells.”

“Most importantly, this combinatorial therapy demonstrates very promising regression (>95 per cent reduction) in the tumour burden and reduced migration of cancer cells to lungs and bones in the tumour-bearing mice,” Ateeq explained.

Elaborating on the strategy of repurposing old approved drugs in the face of escalating costs for developing new cancer drugs, the scientist said the strategy is widely accepted as the safety profiles of these older drugs are well known and accepted in the clinic, and are also inexpensive for conducting clinical trials.

“There are quite a few inspirational success stories about drug repurposing, such as sildenafil, an angina medication, which is now marketed as Viagra for treating erectile dysfunction. Azidothymidine is a failed chemotherapy drug, is another such example, which is now widely used for treating HIV,” she said.

“In our pre-clinical mouse model study, we haven’t observed any signs of toxicity upon administering the drug combination. However, there is an immediate requirement for conducting the well-planned clinical trials using Artesunate in combination with anti-androgens for mCRPC patients,” Ateeq added.

The study is published in the journal Neoplasia and is co-authored by Jessica J. Nunes, Swaroop K. Pandey, Anjali Yadav and Sakshi Goel.

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