Researchers have found a potential new drug target for pancreatic neuroendocrine tumours (PanNETs). Their findings contribute to the development of a new class of drugs and further elucidation of cancer molecular pathways.

The team showed that removing the p110α from of the protein PI3K – either through drugs or genetic manipulation – ultimately killed the tumour.

Of all pancreatic cancers, PanNETs account for less than 5 percent and progress slower compared to exocrine tumours (the other major type of pancreatic cancer). They are characterised by abnormal growth and activity in the islet cells of the pancreas.

In effect, PanNETs overproduce hormones and cause hormone-related syndromes – a condition specifically called functional PanNETs. While non-functional PanNETs – where hormones aren’t overproduced – do exist, the vast majority of PanNETs are functional.

Symptoms of functional PanNETs include indigestion, jaundice, and diarrhea among others.

Typically, cancers involve the deregulation of the PI3K pathway which is directly involved in critical cell processes like division and survival. Either through constant activation, destruction of inhibitors or other genetic mutations, a faulty PI3K pathway is firmly associated with several cancers.

Much of the pharmacologic research on PanNETs have focused on targeting mTOR, another signaling protein in the PI3K pathway.
However, as cancer cells exploit other pathways, there have been increasing reports of resistance against this type of treatment.

Since PI3K has been established as a participant in around 16 percent of PanNETs, the researchers decided to explore that as a possible drug target. To do this, the research team used both live animal models and cell cultures. They deactivated p110α PI3K by using drugs or genetic inactivation.

The researchers found that treatment with a drug that targets all forms of PI3K (not just p110α) stops the growth of the tumor but not the development of new blood vessels.

It prompted the research team to try p110α-specific approaches. When only the p110α form of PI3K was deactivated (either through genetic mutations or using another drug), both growth and vascularization were halted.

Further, the p110α-specific drug also stopped the metastasis of the pancreatic tumor to the liver and lymph nodes.

According to Almira Cleofe, a researcher at the National Institute for Molecular Biology and Biotechnology, the current study is proof of the theory for an alternative path of treatment for PanNETs.

Further, that it proposes a substitute to the currently clinically available treatments makes the study very promising.

However, she continues, though valuable, the study needs further work. Future efforts should concentrate on a more robust experimental design and that produce more conclusive data to allow for an eventual drug development process. MIMS