New hopes for pancreatic tumor from an antipsychotic drug

February 15, 2017, National Research Council of Italy
Molecular model of the drug (in gray) in interaction with some structures of the disordered proteins (in green and orange). Credit: National Research Council of Italy

Ductal carcinoma is the most common pancreatic tumor. Its recovery rates are low, not only due to difficulties of early diagnosis, but also because of the absence of a specific pharmacological treatment. New hopes are coming from a study published in Scientific Reports by the Nanotechnology Institute of CNR, unit of Rende, in collaboration with a team of French and Spanish researchers. A molecule long used to treat anxiety has been found to interfere with the activity of a protein involved in the cancer development process.

Pancreatic cancer is one of the most lethal tumors, and up until now, the only drugs available to fight it are generic chemotherapy treatments. The protein Nupr1 belongs to the special class of 'intrinsically disordered proteins' and its involvement in pancreatic cancer pathology was demonstrated in the 1990s by a French team at the National Institute of Health in Marseille. A molecule capable of inhibiting this protein has been found through a study at the Institute of Nanotechnology of the National Research Council of Italy (Cnr-Nanotec).

"The research has been performed starting from the screening of more than 1000 drugs already approved for various therapeutic indications," says Bruno Rizzuti of Cnr-Nanotec in Rende. "The combined use of experimental techniques and computer simulations has allowed us to identify some of those drugs capable of interacting with the protein Nupr1. In vitro experiments have afterwards shown that the selected compounds were able to lower the vitality of tumor cells, reduce the ability of migration, and completely suppress the possibility of colony formation. The most effective compound has been tested in vivo on human cells transplanted on mice, and proved to completely arrest the development of the disease. The molecule– known as trifluoperazine, and used until now only for its anti-psychotic action – has demonstrated an antitumor efficacy even higher than the most powerful chemotherapy treatments available. Furthermore, this study shows that this new molecule constitutes not only an alternative to such previously known drugs, but can be combined with them to increase the overall therapeutic effect."

'In vitro' decrease of the proliferation of tumor cells with the use of the drug, compared with the use of two typical chemotherapy drugs, or in the absence of a treatment. Credit: National Research Council of Italy

Additionally, this work is an important step on the research into proteins with disordered structure. "According to one of the dogmas of classical biology," says Rizzuti, "the conformation of a protein should be unique and well defined to allow each of these 'molecular machines' to carry out a specific function. Disordered proteins overturn the validity of this principle, and due to their flexible structure, are able to perform multiple functions of cell communication and regulation. However, the absence of well-defined structural elements appeared to be an insurmountable obstacle to proceed to a rational design of selective drugs to hinder their action."

The demonstration of the possibility of identifying active molecules that inhibit disordered proteins is an important step forward from the point of view of basic research, because it changes completely the scenario in the fight against numerous pathologies. In fact, it opens up the concrete possibility of multiplying the number of molecular targets that could be hit through a focused use of pharmaceuticals.

'In vivo' decrease of the tumor growth with the use of the drug (10 mg/kg dose), compared with a reduced dose or in the absence of a treatment. Credit: National Research Council of Italy

Explore further: Reason for pancreatic cancer's resistance to chemotherapy found

More information: José L. Neira et al. Identification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma, Scientific Reports (2017). DOI: 10.1038/srep39732

Related Stories

Reason for pancreatic cancer's resistance to chemotherapy found

November 21, 2016
A pioneering University of Liverpool research team have published a study that identifies the mechanism in the human body that causes resistance of pancreatic cancer cells to chemotherapy.

The PI3K protein: A potential new therapeutic target in pancreatic neuroendocrine tumors

June 20, 2016
Researchers at the Institute of Biomedical Investigation of Bellvitge (IDIBELL), led by Dr. Mariona Graupera, have unveiled the potential therapeutic benefit of a selective inhibitior of the PI3-kinase (PI3K) protein in pancreatic ...

Biologists discover peptides that inhibit metastatic spreading in pancreatic cancer

November 10, 2015
Due to their rapid metastatic spread, pancreatic tumors are among the most aggressive types of cancer. Only three to five percent of patients have a survival rate of five years. A team of KIT researchers has now established ...

Recommended for you

Pregnant? Eating broccoli sprouts may reduce child's chances of breast cancer later in life

August 16, 2018
Researchers at the University of Alabama at Birmingham have found that a plant-based diet is more effective in preventing breast cancer later in life for the child if the mother consumed broccoli while pregnant. The 2018 ...

Scientists discover chemical which can kill glioblastoma cells

August 15, 2018
Aggressive brain tumour cells taken from patients self-destructed after being exposed to a chemical in laboratory tests, researchers have shown.

Three scientists share $500,000 prize for work on cancer therapy

August 15, 2018
Tumors once considered untreatable have disappeared and people previously given months to live are surviving for decades thanks to new therapies emerging from the work of three scientists chosen to receive a $500,000 medical ...

PARP inhibitor improves progression-free survival in patients with advanced breast cancers

August 15, 2018
In a randomized, Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, the PARP inhibitor talazoparib extended progression-free survival (PFS) and improved quality-of-life measures over ...

New clues into how 'trash bag of the cell' traps and seals off waste

August 15, 2018
The mechanics behind how an important process within the cell traps material before recycling it has puzzled scientists for years. But Penn State researchers have gained new insight into how this process seals off waste, ...

RUNX proteins act as regulators in DNA repair, study finds

August 15, 2018
A study by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has revealed that RUNX proteins are integral to efficient DNA repair via the Fanconi Anemia (FA) ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.