Effectors of mTOR-autophagy pathway: targeting cancer, affecting the skeleton

Area of Science:

• Skeletal Biology
• Cancer Therapy
• Cellular Biology

Background:

• Autophagy modulators are being explored for anti-cancer therapies.
• The effects of these modulators on normal tissues, particularly skeletal tissues, require careful evaluation.
• Understanding autophagy's role in skeletal physiology is crucial for assessing potential side effects.

Purpose of the Study:

• To review the role of autophagy in skeletal tissues in the context of anti-cancer therapy.
• To discuss the mTOR-autophagy pathway's involvement in various skeletal cell types.
• To examine potential side effects of targeting mTOR or autophagy in cancer treatment on skeletal health.

Main Methods:

• Review of preclinical studies on autophagy in cancer.
• Review of ongoing clinical trials related to autophagy and cancer.
• Discussion of recent genetic preclinical studies on autophagy in skeletal physiology.
• Focus on the mTOR-autophagy pathway in chondrocytes, osteoblasts, osteocytes, and osteoclasts.

Main Results:

• Inhibiting autophagy is unlikely to significantly reduce bone mass or worsen osteoporosis.
• Autophagy inhibition may lead to articular cartilage damage and osteoarthritis.
• Rapalogs may offer beneficial effects on articular cartilage.
• Modulating mTOR or autophagy during childhood could negatively impact adult height and bone mass acquisition.

Conclusions:

• Targeting autophagy for cancer therapy requires careful consideration of skeletal side effects.
• While bone mass may not be significantly affected by autophagy inhibition, articular cartilage health is a concern.
• Interventions affecting the mTOR-autophagy pathway during development may have long-term consequences on skeletal growth and mass.