How Neoadjuvant Chemotherapy Reshapes Therapeutic Niches in Soft Tissue Sarcomas

About the Project

Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignancies arising from connective tissues such as muscle, fat and nerve sheaths. Comprising more than 100 histological subtypes, STS share a common therapeutic challenge: many patients eventually develop recurrent or progressive disease despite chemotherapy. Neoadjuvant chemotherapy is used in selected patients prior to surgery to reduce tumour bulk, yet the impact of treatment on the biological composition of the tumour remains incompletely understood.

Tumours are not homogeneous masses of cells but complex ecosystems in which cancer cells interact with immune cells, stromal fibroblasts and the extracellular matrix (ECM). The spatial organisation of these components shapes how tumours respond to therapy and how disease progresses. Despite this, most therapeutic target selection has been driven by overall protein abundance, without considering the spatial context in which targets exist or how that context changes after treatment.

ECM remodelling is a key feature of sarcoma biology that influences immune-cell trafficking, drug delivery and target accessibility. Antibody-drug conjugates (ADCs), bispecific antibodies and other emerging targeted agents are entering the sarcoma landscape, but their efficacy may depend not only on target expression but on the spatial architecture of the tumour microenvironment.

The Huang Lab has established a unique proteomic resource from more than 800 clinically annotated sarcoma specimens — the largest proteomic dataset of its kind in soft tissue sarcoma. This project will harness this resource, together with spatial proteomics, digital pathology and multiplexed immunofluorescence, to define how neoadjuvant chemotherapy reshapes therapeutically actionable niches. It will provide the first systematic characterisation of treatment-induced changes in target accessibility and their microenvironmental context, with direct implications for the rational selection of therapies.

Candidates must have, or be on track to receive, a First- or Upper Second- class Honours degree (or a Masters) in Cancer Biology, Biochemistry, or a related biomedical science and have experience in molecular and cellular biology techniques, and must have a basic knowledge of cancer biology and quantitative data analysis.

References

1. Burns, J., Wilding, C.P., Krasny, L., et al. (2023) 'The proteomic landscape of soft tissue sarcomas', Nature Communications, 14, 39486.
2. Cancer Genome Atlas Research Network (2017) 'Comprehensive and integrated genomic characterization of adult soft tissue sarcomas', Cell, 171(4), pp. 950-965.
3. Davis, S., Scott, C., Oetjen, J., et al. (2023) 'Deep topographic proteomics of a human brain tumour', Nature Communications, 14, 7800.
4. Elhanani, O., Ben-Uri, R. and Keren, L. (2023) 'Spatial profiling technologies illuminate the tumor microenvironment', Cancer Cell, 41(3), pp. 404-420.
5. Liu, Y., Dai, Y. and Wang, L. (2026) 'Spatial omics at the forefront: emerging technologies, analytical innovations, and clinical applications', Cancer Cell, 44(1), pp. 24-49.
6. Winkler, J., Abisoye-Ogunniyan, A., Metcalf, K.J. and Werb, Z. (2020) 'Concepts of extracellular matrix remodelling in tumour progression and metastasis', Nature Communications, 11, 5120.
7. Vyas, M. and Demehri, S. (2022) 'The extracellular matrix and immunity: breaking the old barrier in cancer', Trends in Immunology, 43(6), pp. 423-425.
8. Prakash, J. and Shaked, Y. (2024) 'The interplay between extracellular matrix remodeling and cancer therapeutics', Cancer Discovery, 14(8), pp. [contact details available in the full listing].
9. Mullard, A. (2024) 'The antibody-drug conjugate market continues its rapid expansion', Nature Reviews Drug Discovery, 23(1), pp. 3-5.
10. Majzner, R.G. and Mackall, C.L. (2018) 'Tumour antigen escape from CAR T-cell therapy', Cancer Discovery, 8(10), pp. [contact details available in the full listing].