Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment
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Published on: December 1, 2023
Jill W Ivey1, Mohammad Bonakdar2, Akanksha Kanitkar1
1Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University, Blacksburg, VA 24061, USA.
Abstract:
Tumors are highly heterogeneous at the patient, tissue, cellular, and molecular levels. This multi-scale heterogeneity poses significant challenges for effective therapies, which ideally must not only distinguish between tumorous and healthy tissue, but also fully address the wide variety of tumorous sub-clones. Commonly used therapies either leverage a biological phenotype of cancer cells (e.g. high rate of proliferation) or indiscriminately kill all the cells present in a targeted volume. Tumor microenvironment (TME) targeting represents a promising therapeutic direction, because a number of TME hallmarks are conserved across different tumor types, despite the underlying genetic heterogeneity. Historically, TME targeting has largely focused on the cells that support tumor growth (e.g. vascular endothelial cells). However, by viewing the intrinsic physical and chemical alterations in the TME as additional therapeutic opportunities rather than barriers, a new class of TME-inspired treatments has great promise to complement or replace existing therapeutic strategies. In this review we summarize the physical and chemical hallmarks of the TME, and discuss how these tumor characteristics either currently are, or may ultimately be targeted to improve cancer therapies.
Insights
Tumor heterogeneity challenges cancer therapies. Targeting the tumor microenvironment (TME) offers a promising strategy by exploiting conserved physical and chemical hallmarks for improved treatment outcomes.
Area of Science:
- Oncology
- Cancer Biology
- Therapeutic Development
Background:
- Tumors exhibit significant heterogeneity across multiple scales, complicating effective cancer therapies.
- Current treatments often lack specificity, targeting either general cancer cell phenotypes or indiscriminately eliminating cells.
- The tumor microenvironment (TME) presents conserved hallmarks across diverse tumor types, offering a potential therapeutic target despite genetic variations.
Purpose of the Study:
- To review the physical and chemical characteristics of the TME.
- To discuss current and potential therapeutic strategies targeting TME hallmarks.
- To explore TME-inspired treatments as complementary or alternative cancer therapies.
Main Methods:
- Literature review of TME characteristics.
- Analysis of therapeutic approaches targeting TME components.
- Discussion of the potential of TME-inspired treatments.
Main Results:
- Identified key physical and chemical hallmarks of the TME.
- Highlighted conserved TME features across different cancers.
- Discussed the evolution of TME targeting from cellular components to intrinsic properties.
Conclusions:
- The TME's physical and chemical properties represent viable targets for novel cancer therapies.
- Exploiting TME hallmarks can overcome tumor heterogeneity challenges.
- TME-inspired treatments hold promise for enhancing existing therapeutic strategies and developing new ones.
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