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Stromal Mutations: Cause and Consequence in Cancer Biology Virtual Workshop

Visualization of dye labeled dideoxynucleotides generated from DNA fragments of different lengths and sequences

Research aimed at understanding stromal mutations at different stages of tumor evolution – from initiation to metastasis and treatment resistance – lags behind that of traditional cancer cell mutations. Notably, strategies on characterizing the stromal elements – within the mutation-signaling continuum – that are contributing to these various stages of tumorigenesis remain understudied, despite published (yet historical and anecdotal) evidence in support of this notion.

Studies on “stromal effects” are often limited to measuring and/or testing for short term/acute biological and biochemical reprogramming and remodeling events linked to stromal cell state(s), stromal landscape/fibrosis, and immune/inflammatory responses. Missing from the analyses is the longer-term implications and ramifications of stromal cell mutational status – be it somatic or germline and/or nuclear or mitochondrial.

With the recent technological advances in single-cell technologies, multiparameter imaging, and ability to integrate multi-omics with spatial tumor microenvironment context, the cancer research field is now well positioned to interrogate and detect stroma cell mutation(s) as an added – but missing – layer of cancer predispositions, and dynamic complexities.

The Stromal Mutations: Cause and Consequence in Cancer Biology Virtual Workshop was held on May 2 - 3, 2024 and brought together a community of tumor-stromal biologists and technology experts. The objectives of the meeting included:

  • Discuss the state of the science of stromal mutations.
  • Evaluate the technological advancements facilitating scientific progress in the field, along with challenges and limitations.
  • Reach a consensus on key priorities in the field of stromal cell states with an emphasis on pro-tumoral (or tumor suppressive) stroma function driving mutations across the nuclear-mitochondrial genomes.

Documents from the Workshop

Recordings from the Workshop

Day 1 Overview

  • Welcoming remarks - NCI Staff  
  • Overview of why the meeting was exploring stromal mutations (and other genomic alterations) - Dr. Edna (Eti) Cukierman (Fox Chase Cancer Center & Co-Chair of the Workshop)

Stromal Mutations & DNA Repair Session

  • Non-cell autonomous tumor microenvironment (TME) alterations from stromal cell mutations - Dr. Jan van Deursen (Jupiter Bioventures)
  • The role of aged stroma/microenvironment in cancer initiation and progression - Dr. Peter Adams  (Sanford Burnham Prebys)

Systemic Conditions Session

  • Stromal drivers of immune escape during breast tumor progression - Dr. Kornelia Polyak (DFCI)
  • Age-related stromal changes drive breast cancer - Dr. Sheila Stewart (WUSTL)
  • Cancer-associated but not cancer-specific: Activated fibroblasts - Dr. Boris Hinz (University of Toronto)

Day 1 Working Group Discussion 

  • Discussion about the impact of stromal mutations, the effects of germline mutations on the stroma vs. epithelium, and models/technologies to study stromal mutations - Workshop Participants 

Day 2 Overview

  • Overview of the intersection of new technologies, cancer mutations, tumor evolution, and cell plasticity - Dr. Kai Kessenbrock (UC Irvine & Co-Chair of the Workshop)
  • Technologies for investigating stromal mutations - Dr. Nick Navin (MD Anderson Cancer Center)

Tech, Cancer Mutation, Evolution & Plasticity Session

  • Genetic changes in non-epithelial cells of human body - Dr. Fuchou Tang (Peking University)
  • Single-molecule mutation analysis as a genome integrity measure - Dr. Alex Maslov (Albert Einstein College of Medicine)
  • Tracking clonality in tumors and their microenvironments - Dr. Ken Lau (Vanderbilt University)

Day 2 Working Group and Concluding Discussions

  • Discussion about the existence of stromal mutations, technologies for detecting stromal mutations, the role of mutations in the phenotypes of reprogrammed stromal cells, causes of stromal mutations, and mathematical models to understand stromal mutations - Workshop Participants 
  • Concluding discussion about opportunities and challenges in research focusing on the causes and consequences of stromal mutations in cancer biology -  Workshop Participants 
  • Summary & Closing Remarks - Drs. Edna (Eti) Cukierman & Kai Kessenbrock (Co-Chairs of the Workshop)

Social media posts related to the meeting can be found using #SMC3B.

DCB Contacts for the Workshop

For additional information about the Stromal Mutations: Cause and Consequence in Cancer Biology Virtual Workshop, please contact Dr. Mihoko Kai or Christina George. 

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