The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Growth Differentiation Factor 15 (GDF15) is an emerging biomarker and therapeutic target in oncology.
• Elevated GDF15 levels correlate with poor prognosis in various solid tumors, including colorectal, gastric, pancreatic, breast, lung, prostate, and head and neck cancers.
• GDF15 influences tumor progression via PI3K/AKT, MAPK/ERK, and SMAD2/3 signaling, promoting metastasis, immune evasion, and chemoresistance.

Purpose of the Study:

• To review the literature on the role of GDF15 in solid tumors.
• To emphasize the specific role of GDF15 in head and neck cancers.
• To explore therapeutic strategies targeting the GDF15-GFRAL axis.

Main Methods:

• Narrative literature review.
• Focus on GDF15 in solid tumors, particularly head and neck squamous cell carcinoma (HNSCC).
• Analysis of therapeutic targeting of the GDF15-GFRAL axis.

Main Results:

• GDF15 overexpression in HNSCC is associated with aggressive phenotypes, radioresistance, and poor response to chemotherapy and immune checkpoint inhibitors (ICIs).
• GDF15 contributes to metastasis and therapy resistance in colorectal, pancreatic, and prostate cancers.
• Therapeutic targeting of GDF15-GFRAL axis showed promise: ponsegromab improved cachexia outcomes, and visugromab with nivolumab enhanced immune response in ICI-refractory tumors.

Conclusions:

• Further research is needed to fully understand GDF15's role across malignancies.
• Refining patient selection for GDF15-targeted therapies is crucial.
• Evaluating combinatorial approaches with existing cancer treatments is warranted.