Hippo Signaling Pathway

The Hippo pathway is a network of proteins inside cells that controls when cells grow, divide, and die. It acts as a built-in brake on cell multiplication, helping keep organs at the right size and preventing tumors. When this pathway is broken, cells can multiply out of control, which is one of the central problems in mesothelioma.

Origin

The pathway was first discovered in fruit flies in the 1990s and early 2000s, where mutations caused massive tissue overgrowth, flies that looked unusually large and skin-folded, prompting researchers to name the core gene 'Hippo' after the hippopotamus. The same pathway was later identified in humans and connected to cancer biology, including mesothelioma, in the late 2000s and 2010s.

Significance in Asbestos Context

The Hippo pathway is one of the most frequently disrupted systems in pleural mesothelioma. The gene NF2 (also called Merlin) and the gene LATS2, both core members of this pathway, are commonly mutated or deleted in mesothelioma tumors, which switches off the body's normal brake on cell growth. When the brake is off, a protein called YAP becomes overactive and drives tumor cells to keep dividing. Understanding this pathway matters to patients because it is now a major target of clinical trials: drugs called TEAD inhibitors and YAP inhibitors are being tested specifically in mesothelioma patients whose tumors have NF2 or LATS2 changes. If your tumor has been genetically tested, ask your oncologist whether Hippo pathway alterations were found and whether a clinical trial targeting this pathway is appropriate for you.

Example Sentence

The molecular report on her pleural biopsy showed an NF2 mutation, indicating Hippo pathway disruption, which made her eligible for a clinical trial of a TEAD inhibitor.

Related Terms

NF2, BAP1, YAP/TAZ, TEAD Inhibitor, Pleural Mesothelioma, Tumor Suppressor Gene

Notes

• Ask your oncologist whether your tumor has had molecular or genomic testing, and specifically whether NF2, LATS1, LATS2, or YAP alterations were identified.
• If Hippo pathway alterations are present, ask about open clinical trials of TEAD inhibitors (such as VT3989 or IAG933). These are among the most active areas of mesothelioma drug development.
• Request a copy of any tumor sequencing report (often called NGS, FoundationOne, Tempus, or Caris) for your personal records; these reports can also support your legal claim by documenting the specific biology of your disease.
• Hippo pathway changes are most common in pleural mesothelioma but have also been reported in peritoneal mesothelioma, relevant to either diagnosis.