The new year has begun with two papers announcing progress against relatively rare, but unusually deadly, triple-negative breast cancers. Since it is estimated these will be responsible for hundreds of thousands of deaths in the course of the year, success for one or both approaches can't come fast enough.
The last few decades have seen amazing progress against breast cancers, with survival rates soaring. However, much of this has been done by finding ways to block the hormones or growth factors that encourage breast cancers to grow. Triple-negative breast cancers, on the other hand, get their name because they test negative to estrogen, progesterone, and human epidermal growth factor receptors, leaving nothing obvious to block. They only account for around 15 percent of breast cancers, but have become a much larger proportion of deaths.
As the easier problems were solved, however, focus turned to the harder ones and two teams have shown success in pre-clinical trials, with at least one of the approaches also having potential against certain cancers elsewhere in the body.
At the moment triple-negative breast cancers are treated using drugs called RAF and MEK inhibitors. These usually work well against the tumors at first. Unfortunately, the cancers often quickly develop resistance to these drugs. In Cell Reports a team based at Mount Sinai Health System, New York have announced that drugs known as SHP2 inhibitors slow, and potentially stop, the development of resistance in cancers in human cell cultures and in mice.
Some pancreatic, lung, and colorectal cancers have the same underlying cause as triple-negative breast cancers, and the paper's authors hope the same approach will prove effective against these. It's unlikely there will ever be a single cure for cancer, since cancer is so many different diseases, but an effective treatment for several different forms would be as close as any one line of research is likely to get.
The failure rate for potential medications to make it from preclinical enthusiasm to widespread use is high enough it doesn't pay to get too excited about any one approach, so its best to have some spares. Just one day after the paper on SHP2 inhibitors came out, Princeton University's Professor Yibin Kang announced the potential of the protein Tinagl1 in the journal Cancer Cell. Tinagl1 blocks two of the pathways triple-negative cancer cells use to grow and spread beyond the initial tumor to take hold in organs where they become lethal.
Tinagl1 is a naturally occurring protein. Kang and colleagues noticed samples of breast cancers with lower Tinagl1 gene expression were associated with more rapid progression and shorter survival times. They found engineering mouse cancer cells to express more Tinagl1 slowed their growth. Even more encouragingly, Tinagl1 given to mice with mammary cancers slowed the growth of the tumors and stopped the cancer spreading to the lungs – even in cases where spreading had already begun.
“People have tried to block the spread of this form of cancer but attempts so far have failed because if you try one approach, the cancer cells compensate by finding a way to escape," Kang said in a statement. “With this new approach, the treatment blocks both pathways at the same time.”
There may be much further to go, but this is a promising start to the year.
