UC San Diego Health Sciences News

Liver cancer: paradigm or paradox

For most patients diagnosed with hepatocellular carcinoma (HCC), a main type of liver cancer, survival is typically measured in months. It’s an incredibly fast-moving disease: Tumors can double in size every 60 to 90 days, a time period that, coincidentally, also reflects the mean survival rate of diagnosed, symptomatic patients.

And yet, in mouse models of the HCC, the genes known to drive oncogenesis also appear to possess suppressive powers as well. They both spur and block development of the disease. It’s a confounding contradiction – and one that must be resolved before truly effective therapies – let alone a cure – can be found for HCC.

In a review published in the February issue of the journal Cancer Cell, Gen-Sheng Feng, PhD, professor of pathology and molecular biology in the University of California, San Diego School of Medicine, argues that the conflicting roles of molecules in hepatocarcinogenesis are not really paradoxical, but rather evidence that the approach to studying and treating HCC requires a paradigm shift.

“In mouse models, we’ve found that if you over-activate certain genes, you cause liver cancer. We’ve also discovered that if you delete those genes, that causes cancer. The liver is a far more complicated organ than people once thought. It requires far more complicated remedies.”

Part of that complication lies in the nature of the liver itself. Unique among organs, the liver is capable of total regeneration: It can completely repair damaged tissue without scarring. For example, within two weeks of a partial hepatectomy – a procedure to surgically remove up to two-thirds of a diseased organ – the remaining liver may reconstitute its original mass.

But that sort of ability (a necessity given its job of filtering out toxins and other undesirables in the bloodstream and its singularity – it has no back-up twin like the kidneys or lungs) comes at a price, said Feng. “Anything that causes cell death in the liver can induce cancer through the regenerative process.”

In other words, cancer is essentially a disease of cell growth run amok. And few places in the body are more fertile for cell growth than the.

Traditional chemotherapy for liver cancer is generally ineffective. Some drugs work, but not for long. The disease soon recurs. Feng suggests that complete eradication of cancerous liver cells requires a cocktail of drugs aimed at multiple targets in liver cells. The liver functions by achieving homeostasis or an equilibrium of many factors, some likely unknown. Effective treatment will also require a complex pharmaceutical balancing act.

Doing so will take time, which HCC patients lack. The incidence and fatality rates for HCC are rising, unlike other types of cancer. It’s the third most common cancer worldwide. For diagnosed patients, there’s no time to spare.