Innovative therapy that “tricks” and destroys cancer cells advances to clinical trial

11 Apr 2022
Innovative therapy that “tricks” and destroys cancer cells advances to clinical trial

A novel therapy studied at the Medical College of Wisconsin (MCW) Cancer Center has led to a clinical trial for the treatment of glioblastoma, a rare and aggressive form of brain cancer, yet the most common primary brain tumour in adults.

Despite decades of research globally, only incremental gains have been made to extend or enhance quality of life for patients with glioblastoma. Treatment options are limited and typically include a combination of surgery, radiation therapy, and chemotherapy.

Now, a new clinical study open at Froedtert & the Medical College of Wisconsin will evaluate an alternative treatment that is administered orally.

The treatment evolved from years of research led by Christopher Chitambar, MD, and his lab to study iron-dependent processes in cancer biology and the mechanisms by which gallium compounds target iron metabolism and block malignant cell growth.

In preclinical studies, Drs. Chitambar and Kathleen Schmainda, PhD, discovered that when administered intravenously, gallium maltolate (GaM) significantly slowed the growth of glioblastoma in a rat brain tumour model.

Additional studies showed that GaM, administered orally to glioblastoma-bearing rats, significantly reduced the size of their tumours and prolonged survival.

GaM, originally developed by Harvard and Stanford educated scientist Lawrence R. Bernstein, PhD, is an orally available form of the metal gallium, which, in the body, shares many chemical properties with the highly oxidized form of iron, Fe(III).

Numerous studies examining the relationship between iron and cancer show that increased levels of iron in the body can be associated with increased cancer risk and severity, due to cancer cells’ dependence on iron to multiply and spread.

Because of gallium’s similarity to Fe(III) (the form of iron cancer cells take up), cancer cells take up gallium instead of iron, preventing their multiplication, ultimately leading to their death.

“The discovery that GaM has anticancer activity against glioblastoma in pre-clinical studies is extremely exciting; it opens the door for developing it as a drug for treatment of glioblastoma in patients,” says Christopher Chitambar, MD, Emeritus Professor of Medicine and Biophysics, Division of Haematology and Oncology at MCW.

“The anticancer mechanism of GaM applies to other solid tumours as well,” he adds.

Source: Medical College of Wisconsin