‘Undruggable’ cancers treated by slowing growth could be 'holy grail', researchers say

Cancers which have been written off as “undruggable” by scientists because they appear impervious to conventional treatments have had their growth slowed or even reversed by an experimental new drug.

Lab experiments with lung, skin, colon and pancreatic cancer cells found the recently discovered drug could drastically slow their growth, with similar effects seen in test in animals.

It works by targeting a major pathway in cancer growth where DNA mutations have broken the system for telling cells when to start and stop dividing, jamming it on and sending growth into overdrive.

This can happen in a variety of ways and these defects – in the RAS/MAPK cell division pathway – are found in around half of all human cancer cases, but no drug has yet been able to target them.

“RAS/MAPK is one of the most important cancer signalling pathways, but so far most attempts to develop targeted drugs against this pathway have ended in failure, which has led some people to start calling it a ‘holy grail’ of cancer therapy,” said Dr Trever Bivona, senior author of the study in Nature Cell Biology and an oncologist at the University of California in San Francisco.

Instead of targeting the cells to prevent this rampant growth, Dr Bivona and his team identified that in some of these cancers, cells are simply hypersensitive to growth signals.

This is driven by a molecule called SHP2, which switches on the growth pathway and a drug which can block this step could prevent the whole chain of unchecked cell division from launching.

In a partnership with the drug discovery group Revolution Medicines, they trialled new chemicals on various cell types and found one, called RMC-4550 could drastically slow growth, or even kill cancer cells.

“We were able to demonstrate that this compound successfully suppressed the RAS pathway in the rodent tumour models and that this not only slowed tumour growth but even led to tumour regression in some cases, with minimal side effects in the animals,” Dr Bivona said.

“This was very exciting to me because it meant that the compound was not just arresting cell growth but actually killing cancer cells.”

Revolution Medicines is now hoping to launch human trials next year, first to test if the drug is safe and whether its effects are replicated.

“The implications of being able to block SHP2 are broad and may extend to more types of cancer than seen in the present study,” Dr Bivona added. “Almost every major oncogene I can think of coopts this pathway in one way or another, and many of these cancers currently have no effective targeted therapies or eventually develop resistance to available targeted therapies.”