Targeting the JAK/STAT pathway in solid tumors.

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Aberrant activation of signal transducer and activator of transcription (STAT) proteins is implicated in solid tumor development and progression.
• STAT proteins, as transcription factors, are challenging to target directly for cancer therapy.

Purpose of the Study:

• To review the strategy of targeting Janus kinases (JAKs), upstream activators of STATs, for decreasing STAT activation in solid tumors.
• To summarize the preclinical and clinical evidence for JAK inhibitors in solid tumor treatment.

Main Methods:

• Review of preclinical studies in solid tumor cell line and in vivo models.
• Analysis of clinical trial data for JAK inhibitors in solid tumors.
• Examination of existing FDA-approved JAK inhibitors for potential repurposing.

Main Results:

• JAK inhibitors decrease STAT activation, cell proliferation, and survival in preclinical solid tumor models.
• JAK inhibitors demonstrate anti-tumor effects in vivo and sensitize tumors to other therapies.
• Ten JAK inhibitors are in clinical trials for solid tumors; two are FDA-approved for other conditions and well-tolerated.

Conclusions:

• JAK inhibition is a viable therapeutic strategy for targeting the JAK/STAT pathway in solid tumors.
• Further clinical trials are warranted to assess the efficacy of JAK inhibitors in solid tumor patients.