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A doctor talking to a woman. A doctor talking to a woman.

Soft tissue sarcoma

A rare cancer.

A major clinical challenge.

An arrow pointing downward.

Unraveling the Science of Soft Tissue Sarcoma

The interplay between tumor and stroma may contribute to poor survival outcomes in cancer.1,2 Soft tissue sarcoma (STS) is among the most distinct and complex types of cancer.3 In recent decades, therapeutic advancements have been limited and there has been minimal change in overall survival.4-6 How can we better understand the nature of this disease? The stroma—not just the tumor—may be a factor.1

What makes soft tissue sarcoma so clinically challenging?

A rare and complex cancer.

Soft tissue sarcomas (STSs) are a group of rare, malignant solid tumors of more than 50 histologic subtypes that arise from connective tissues of the body.3,7

STS presents in many ways.

Diagnosis can be especially challenging due to its clinical and pathological diversity.3,8

  • Tumors often present as a growing painless mass, and symptoms can go unrecognized or misinterpreted for a period of time before diagnosis3,9
  • 40% to 50% of patients diagnosed will develop metastatic disease10

Therapeutic advancements have been limited.

In recent decades, there has been minimal change in overall survival, and few therapeutic options have been developed to address the unique challenges of the disease.4-6

Estimated survival graph Estimated survival graph

Estimated 5-year observed survival at stage IV is 10% to 20%12

* Includes heart cancer, which comprised <1% of sarcoma types.11

Stroma tumor

Where does the stroma end and the tumor begin?

A relationship born from a common lineage.

Cells in the STS tumor and stroma all originate from a mesenchymal cell type.13,14

In contrast to typical carcinoma pathology, studies have demonstrated that some sarcoma subtypes show a very limited distinction between the tumor and stroma.15

  • Sarcoma tumor cells may not appear in clusters and may be more evenly distributed in the microenvironment15

Sarcoma (leiomyosarcoma)15

Tumor microenvironment with less distinction between the tumor and stroma

Stroma tumor

Carcinoma (breast)15

Clustered tumor cells with more distinction between the tumor and surrounding stroma

Stroma tumor

Interplay and signaling pathways in cancer.

Tumor cells do not act in isolation, but instead subsist with stromal components that can include fibroblasts, endothelial cells, pericytes, leukocytes, and extracellular matrix.16

Crosstalk between tumor cells and stromal cells may contribute to tumorigenesis, from origin to progression and development of metastases.1,14

  • Growth factors expressed on tumor cells and stromal cells bind to receptors and can induce autocrine and paracrine signaling in cellular pathways2,17
  • In STS, growth factors and receptors linked to mesenchymal biology are expressed on tumor cells and stromal cells, and are associated with a poor prognosis16,17
  • Shared and overlapping biological features among tumor and stromal cells are an important area of ongoing research in STS5,16,17

Lilly Oncology is working to unravel the science of STS by improving our understanding of the relationship and shared signaling pathways between the stroma and the tumor.2

Sights on Sarcoma

Dr. Brian Van Tine offers insights into the challenges of STS, and discusses how enhanced research efforts can hold real promise for patients.

Sights on Sarcoma

Dr. Gina D'Amato discusses the poor prognosis and limited options for patients with metastatic disease and explores the biological factors that may play a role in its progression.

References

  1. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19:1423-1437.
  2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.
  3. Fletcher CDM, Sundaram M, Rydholm A, Coindre JM, Singer S. Soft tissue tumours: Epidemiology, clinical features, histopathological typing and grading. In: Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press; 2002:12-18.
  4. Ravi V, Patel S, Benjamin RS. Chemotherapy for soft-tissue sarcomas. Oncology. Cancer Network. http://www.cancernetwork.com/oncology-journal/chemotherapy-soft-tissue-sarcomas. Published January 15, 2015. Accessed September 23, 2015.
  5. Quesada J, Amato R. The molecular biology of soft-tissue sarcomas and current trends in therapy. Sarcoma. 2012:1-16. doi:10.1155/2012/849456.
  6. American Cancer Society. Sarcoma: Adult soft tissue cancer. http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/ detailedguide/sarcoma-adult-soft-tissue-cancer-what-is-cancer. Atlanta, GA: American Cancer Society. Updated March 2015. Accessed September 16, 2015.
  7. Comprehensive Cancer Center, University of Michigan Health System. Sarcoma awareness. http://www.mcancer.org/sarcoma/sarcoma-awareness. Accessed October 18, 2015.
  8. Grimer R, Judson I, Peake D, Seddon B. Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010:1-15. doi: 10.1155/2010/506182.
  9. National Cancer Institute: PDQ® Adult soft tissue sarcoma treatment. Bethesda, MD: National Cancer Institute. http://www.cancer.gov/types/soft-tissue-sarcoma/patient/adult-soft-tissue-treatment-pdq. Updated April 2, 2015. Accessed September 16, 2015.
  10. Italiano A, Mathoulin-Pelissier S, Le Cesne A, et al. Trends in survival for patients with metastatic soft-tissue sarcoma. Cancer. 2011;117:1049-1054.
  11. SEER Cancer Statistics Factsheets: soft tissue including heart cancer. National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/statfacts/html/soft.html. Accessed December 7, 2015.
  12. Nedea EA, DeLaney TF. Hematology/Oncology Clinics of North America: Sarcoma and skin radiation oncology. Hematol Oncol Clin North Am. 2006;20:401-429.
  13. Rocchi L, Caraffi S, Perris R, Mangieri D. The angiogenic asset of soft tissue sarcomas: a new tool to discover new therapeutic targets. Biosci Rep. 2014;34:651-661.
  14. Grisendi G, Bussolari R, Veronesi E, et al. Understanding tumor-stroma interplays for targeted therapies by armed mesenchymal stromal progenitors: the Mesenkillers. Am J Cancer Res. 2011;1:787-805.
  15. Tomlinson J, Barsky SH, Nelson S, et al. Different patterns of angiogenesis in sarcomas and carcinomas. Clin Cancer Res. 1999;5:3516-3522.
  16. Pietras K, Östman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res. 2010;316:1324-1331.
  17. Heldin CH. Targeting the PDGF signaling pathway in tumor treatment. Cell Commun Signal. 2013;11:1-18. doi:10.1186/1478-811X-11-97.