New Target, Drug Potential Found for Colon Cancer

LONDON – British scientists said they have found a new target for treating advanced bowel cancer which could also be used to identify tumors that will respond to Bristol Myers Squibb's cancer drug Sprycel.

In a study in the Journal of the National Cancer Institute, researchers from the Institute of Cancer Research (ICR) found that Sprycel, known generically as dasatinib and already used in other cancers, reduced bowel cancer cell growth in the lab by blocking the effects of an enzyme called lysyl oxidase, or LOX.

"The enzyme LOX is the one that is important for the cancer to spread, and if you block that then you can stop the cancer from growing," Janine Erler, who led the study, said in an interview.

Erler said this followed previous work in which her team found LOX played a role in the spread of breast cancer, leading them to suspect it may also be key in other tumors.

The latest study confirmed LOX was also important in bowel cancer growth and spread, Erler said, and showed cell growth increases in tumor cells with high levels of LOX, while low levels of LOX lead to limited cell growth.

The team also showed LOX was activating a molecule called SRC to promote cancer growth and spread, a finding that led them to look at Sprycel, which is known to block SRC function and is already being used to treat patients with chronic myeloid leukemia, or CML.

"Our findings have revealed two potential new avenues for combating advanced bowel cancer, either with existing SRC inhibitor treatments or with drugs currently being developed to target LOX," Erler said.

She said experimental drugs to block LOX were only in the earliest stages of development and were not yet ready for testing beyond the laboratory. But she said the findings should open up a way to explore using Sprycel or other SRC inhibitors to help colon cancer patients.

Bowel cancer, also known as colorectal or colon cancer, is the third most common cancer worldwide, causing 529,000 deaths a year. There are few effective drugs available for colon cancer which has spread, and patients have a poor prognosis.

Erler's study showed that a test for levels of LOX could be used to single out cancers whose SRC molecules are highly activated, therefore identifying patients most likely to benefit from treatment with Sprycel or other SRC inhibitors.

Pfizer's bosutinib, which is currently in late stage trials for CML, is also known to block SRC, as is Ariad's ponatinib, which is undergoing mid-stage testing.

Malcolm Dunlop of Britain's Medical Research Council (MRC), which funded the study, said finding a way to prevent the metastatic spread of tumors was crucial if doctors were going to be able to reduce the number of deaths from bowel cancer.

"The discovery that controlling the enzyme LOX could influence colorectal cancer cell growth is very encouraging," he said in a statement.