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CD44 in Ovarian Cancer Progression and Therapy Resistance-A Critical Role for STAT3

Antons Martincuks1, Pei-Chuan Li1, Qianqian Zhao1

  • 1Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, United States.

Frontiers in Oncology
|December 18, 2020
PubMed

Insights

Ovarian cancer is deadly due to recurrence and chemoresistance. Targeting CD44 and STAT3 interactions may improve treatment by affecting tumor growth, spread, and the tumor microenvironment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Ovarian cancer is a lethal gynecologic malignancy with poor survival rates, often due to recurrence and chemoresistance.
  • CD44, a transmembrane receptor, is implicated in cancer progression, stem cell maintenance, and chemoresistance.
  • CD44 signaling interacts with pathways like signal transducer and activator of transcription 3 (STAT3), both crucial in ovarian cancer.

Purpose of the Study:

  • To review the functional crosstalk between CD44 and STAT3 in human malignancies, focusing on ovarian cancer.
  • To explore how CD44 and STAT3 influence tumor cell-intrinsic processes and the tumor microenvironment.
  • To summarize current CD44 therapeutic strategies and suggest improved ovarian cancer treatments.

Main Methods:

  • Literature review of existing evidence on CD44 and STAT3 interactions.
  • Analysis of their roles in cancer progression, metastasis, and chemoresistance.
  • Examination of their impact on the tumor microenvironment, including angiogenesis and immunosuppression.

Main Results:

  • CD44 and STAT3 intrinsically drive ovarian cancer progression and metastasis.
  • These proteins foster a pro-tumorigenic tumor microenvironment, promoting angiogenesis, immunosuppression, and metabolic reprogramming.
  • Evidence highlights the significant role of their crosstalk in treatment resistance.

Conclusions:

  • The interplay between CD44 and STAT3 is critical for ovarian cancer progression and therapeutic resistance.
  • Targeting this crosstalk offers a promising strategy for overcoming chemoresistance and improving patient outcomes.
  • Further research into combined therapeutic approaches targeting CD44 and STAT3 pathways is warranted.
Keywords:
CD44STAT3angiogenesischemoresistanceimmunosuppressionovarian cancertumor microenvironmenttumor progression

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