Your new experience awaits. Try the new design now and help us make it even better

REVIEW article

Front. Oncol.

Sec. Pediatric Oncology

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1663975

Pediatric Tumor Microenvironment: Developmental Dynamics and Therapy Resistance

Provisionally accepted
Noreen Grace GeorgeNoreen Grace George1Bhavika RishiBhavika Rishi1Himanshu DhandaHimanshu Dhanda1Gratial Theres JosephGratial Theres Joseph1Sandeep Kumar SwainSandeep Kumar Swain1Manpreet KaurManpreet Kaur1Neetu KushwahaNeetu Kushwaha1Raj KamalRaj Kamal1Pranay TanwarPranay Tanwar2Sufian ZaheerSufian Zaheer3Shamsuz ZamanShamsuz Zaman4Amitabh SinghAmitabh Singh3Fouzia SirajFouzia Siraj4*Aroonima MisraAroonima Misra1*
  • 1ICMR-National Institute of Child Health & Development Research, New Delhi, India
  • 2All India Institute of Medical Sciences New Delhi, New Delhi, India
  • 3Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
  • 4ICMR-Centre for Cancer Pathology, New Delhi, India

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

The tumor microenvironment (TME) in pediatric cancers is profoundly shaped by the unique biological 18 context of childhood development. Unlike adult tumors, pediatric malignancies arise in growing 19 tissues, where evolving immune systems, dynamic stromal elements, and distinct hormonal and 20 microbial influences converge to create highly specialized tumor-supportive niches. This review 21 explores how developmental processes interact with tumor biology to drive immune evasion, therapy 22 resistance, and disease progression. Key mechanisms such as extracellular matrix remodeling, 23 metabolic reprogramming, and epigenetic plasticity are highlighted as critical contributors to treatment 24 failure. Also, the recent advancements in nanomedicine, circulating markers makes it possible for 25 interventions to be more precise and age-informed. The integration of developmental biology along 26 with tumor ecosystem can emphasis the necessity of developing treatment plans that take into account 27 risks and advantages associated with pediatric TME.

Keywords: pediatric tumor microenvironment, therapeutic resistance, immune checkpoint inhibition, ECM, Developmental oncology

Received: 11 Jul 2025; Accepted: 14 Oct 2025.

Copyright: © 2025 George, Rishi, Dhanda, Joseph, Swain, Kaur, Kushwaha, Kamal, Tanwar, Zaheer, Zaman, Singh, Siraj and Misra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Fouzia Siraj, fouziasiraj2009@gmail.com
Aroonima Misra, dr.aroo.2402@gmail.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material