Categories: CombinationSmart

Smart combination therapy for liver cancer tackles drug resistance

Credit: CC0 Public Domain

Liver cancer is one of the most common cancer types worldwide and is especially common in China. A collaborative effort between researchers at the Netherlands Cancer Institute and Shanghai using CRISPR/Cas has led to the discovery that insensitivity to a liver cancer drug can be prevented if it is given in combination with a second drug.

Finding the alternative pathway in the cancer cell

More and more —known as targeted therapy—inhibit the effects of DNA errors in the cell. Unfortunately, cancer cells often are—or become—resistant to these drugs. They then continue to divide via an alternative signaling route in the cell. Molecular cancer researcher Rene Bernards exposes these routes in cancer cells by blocking all routes off, one by one, using genetic techniques such as CRISPR/Cas.

Bernards first discovered one of these pathways in 2012. He wanted to know why a specific drug did nothing for a particular form of colon cancer that is difficult to treat, while working fine for melanoma involving exactly the same DNA mutation. Then he figured out that combining the first drug with a second blocks this pathway, a revolutionary discovery, which has led to a life-extending combination that is now used worldwide. It also led to a search for other alternative signaling pathways as well as new combination therapies for other types of cancer.

Combination therapy for liver cancer overcomes resistance

This week, Bernards, his Shanghai-based postdoc Haojie Jin, and their colleagues in Europe and China describe a similar resistance mechanism, in in the journal Nature. They discovered why the drug lenvatinib, one of the few targeted drugs on the market for liver cancer, shows no effect at all in 75-80 percent of patients.

The interferer turned out to be EGFR, a growth factor receptor, that—as the researchers observed—is activated in liver as soon as the drug lenvatinib is administered, thereby spurring cell division. In mouse models, the researchers then witnessed that precisely those tumors that were resistant to lenvatinib from the start, did indeed activate the EGFR.

But they also discovered that it is possible to override this resistance in as well as mice by combining lenvatinib with another drug, gefitinib, which inhibits EGFR. This is an existing that is already being used to treat lung cancer, for example.

Six hundred beds for liver cancer

Liver cancer is relatively rare in the West, although certain lifestyle factors have led to an increase in its occurrence. In Africa and Asia, however, liver cancer, mainly as a result of hepatitis B and C, is a major problem, and half of the world’s deaths related to liver cancer occur in China. Because Rene Bernards holds a part-time chair at Jiao Tong University in Shanghai postdoc Hoajie Jin’s home university, they were able to immediately set up an first-in-human clinical study at the Eastern Hepatobiliary Surgery Hospital in Shanghai. This hospital alone has 600 beds for patients with cancer.

Proof-of-concept study

This phase 1 proof-of-concept study involved twelve patients who previously did not respond to treatment with lenvatinib and who had large amounts of EGFR in their tumor. A significant reduction of the tumor was observed in four of the twelve. The cohort of patients is now being expanded to thirty. After that, larger clinical studies are needed before this can be us

Read More

News Bot

Share
Published by
News Bot

Recent Posts

Biggest U.S. earthquake in more than 50 years strikes Alaska—here’s what we can learn

ScienceNewsThe magnitude 8.2 earthquake did little damage, and it provides an opportunity for scientists to…

45 mins ago

Jamie Lee Curtis Shares Her and Christopher Guest’s 25-Year-Old Child Is Transgender

Jamie Lee Curtis Reacts to Viral 2021 Golden Globes LookJamie Lee Curtis has revealed that…

46 mins ago

The Epic Story of Princess Diana’s Wedding Dress: 3 Months, 25 Feet of Train and a Major Fashion Legacy

Fox Photos/Getty Images"Hello, it's me."  So was the greeting that couturier David Emanuel heard on the…

46 mins ago

Gymnast Suni Lee Wins Gold as Teammate Simone Biles Cheers Her in Tokyo Olympics Stands

A golden moment for Suni Lee! The gymnast won the individual all-around competition at the…

46 mins ago

Selling Sunset’s Chrishell Stause and Jason Oppenheim Reveal They’re Dating

Chrishell Stause & Jason Oppenheim Are DATING!Chrishell Stause and Jason Oppenheim are sailing off into…

46 mins ago

Watch Married at First Sight’s Jessica and Austin Reveal They Are Expecting a Baby

In a sneak peek at Married at First Sight: Couples’ Cam, Jessica documented the moment…

46 mins ago