The science behind FORE-8394

If you are a FORE-8394 clinical trial participant or candidate, you probably have questions about how the drug works. Here are the key facts.

FORE-8394 targets cancer cells with BRAF mutations:
FORE-8394 is a small molecule that targets cancer cells with a mutated BRAF gene. Unlike conventional chemotherapy, this targeted therapy spares healthy cells, as their BRAF gene is not mutated.
Blocking mutant proteins can slow tumor growth:
Our cells’ BRAF gene contains instructions for making BRAF proteins. BRAF proteins are large molecules that work with other proteins to relay a signal that tells the cell that it’s time to grow and divide. Changes, or mutations, to the BRAF gene can cause the BRAF protein to keep this signal permanently on, meaning that affected cells may multiply uncontrollably and possibly form a cancerous tumor. FORE-8394 is designed to slow tumor growth by locking into and silencing mutant BRAF proteins, thereby switching off the rogue cell division signal.
Targeted therapy differs from chemotherapy:
FORE-8394 is designed to block only mutated BRAF proteins. Most BRAF mutations are not inherited; instead, they usually develop after birth and only in certain cells. FORE-8394 can slow tumor growth by blocking the multiplication of only these mutant cells, while sparing cells with normal BRAF genes. This selectivity means fewer side effects than traditional chemotherapies, which kill any rapidly reproducing cell, including healthy ones.
FORE-8394 differs from older BRAF-inhibitors:
Studies show that FORE-8394 is potentially safer and more effective than first-generation BRAF-inhibitors. These first-generation inhibitors only target the most common BRAF mutations, and paradoxically, can even amplify cancerous activity in certain mutant cells. By contrast, FORE-8394 appears to inhibit a wider range of BRAF mutations, both common and rare, and does not trigger the drug resistance seen with first-generation inhibitors.
For more information about the trial:

Fore is running a clinical trial open for BRAF fusions patients and BRAF mutant glioma patients, as detailed in the NCT02428712 study protocol.
For information about the study or to check suitability for enrolling as a new patient, please contact us via the attached form or at trials@fore.bio.