Washington : Researchers have identified a potential biomarker and therapeutic target for gastric cancer, paving the way for diagnosis and possible treatments for the second deadliest cancer in the world.
Scientists have shown that the hormone receptor GHRH-R could be a potential biomarker for gastric cancer, enabling earlier diagnoses and better staging.
They also found that the GHRH-R antagonist MIA-602 inhibited gastric cancer in both cell lines and human xenografts.
“The GHRH receptor is both a biomarker that can confirm prognosis and a therapeutic target. Gastric cancer is the second deadliest in the world we need new approaches,” said Andrew V Schally from the University of Miami Miller School of Medicine in the US.
Though occurring less frequently than other cancers in the US, gastric cancer kills around 700,000 people worldwide each year, second only to lung cancer, researchers said.
The problem is two-fold: diagnoses are often delayed, allowing the cancer to spread, and there are few effective treatments.
Chemotherapy is often ineffective and surgery works best when the disease is caught early.
The two-pronged study combined epidemiology and lab work. Researchers studied nearly 1,000 tumours from patients in China and other parts of the world. They linked the prevalence of GHRH receptors with larger, more-aggressive tumours and lower overall survival.
“We found that measuring GHRH receptor overexpression could be very useful, both for prognosis and identifying the stage of the cancer,” said Schally.
The GHRH receptor also offers a potential therapeutic target. The receptor helps drive the aberrant growth associated with gastric and other cancers.
Schally and his collaborators have been working for many years to develop an inhibitor that will reduce or eliminate these signals, culminating in the peptide drug candidate MIA-602.
In the study, MIA-602 inhibited gastric cancer growth in cell lines and human tumour xenografts, decreasing both tumour size and weight.
Further research showed that MIA-602 works by mitigating a network of proteins controlled by PAK1, ultimately inhibiting the well-known inflammatory proteins STAT and NF- kappa B.
In addition, MIA-602 showed no evidence of side effects. While developing an effective agent against gastric cancer would be an enormous advance, MIA-602 may also benefit other patients.
“This compound is an efficient inhibitor for a variety of cancers, including lung, prostate, breast and brain,” said Schally.
Schally hopes the therapy will soon move forward into clinical trials
The study was published in the journal PNAS.