Breaking Through
Tumor Barriers™

The Hostile Tumor Microenvironment

Many solid tumors promote a hostile, immunosuppressive, fibrotic TME that limits tumor penetration capacity of antitumor immune cells and drug delivery—driving drug resistance and limiting durability of response to treatment.^1-4

TGF-β: A Central Driver of TME Barriers⁵

TGF-β is a key cytokine centrally implicated in progression, metastasis, and resistance in solid tumors, that drives⁵:

Fibrosis
Angiogenesis
Epithelial-mesenchymal transition (EMT) and associated EGFR inhibitor resistance
Immunosuppressive and immune-exclusive TMEs

By enacting a barrier to tumor penetration of immune cells, TGF-β expression drives resistance to legacy or surface-acting mechanisms, including chemo, radiation, EGFR, and immune checkpoint inhibitors (ICIs).^6-8

When TGF-β is left unchecked, the resulting hostile, protumoral activity limits the long-term durability and effectiveness of legacy therapies.^6-8

Tumor Penetration™: The Next Advancement

Localized locking of TGF-β breaks down TME barriers with the potential to promote tumor penetration capacity in tumors expressing TGF-β and may enable deep and durable outcomes for patients.⁵

Bicara is pioneering the science of Tumor Penetration in solid tumors™.

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EGFR, epidermal growth factor receptor; TGF-β, transforming growth factor-beta.

References: 1. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6:92. doi:10.1038/s41572-020-00224-3 2. Batlle E, Massagué J. Transforming growth factor-β signaling in immunity and cancer. Immunity. 2019;50(4):924-940. doi:10.1016/j.immuni.2019.03.024 3. Neuzillet C, Tijeras-Raballand A, Cohen R, et al . Targeting the TGFβ pathway for cancer therapy. Pharmacol Ther. 2015;147:22-31. doi:10.1016/j.pharmthera.2014.11.001 4. Chandler C, Liu T, Buckanovich R, Coffman L. The double edge sword of fibrosis in cancer. Transl Res. 2019;209:55-67. doi:10.1016/j.trsl.2019.02.006 5. O’Connell BC, Nair P, Nair R, et al. Ficerafusp alfa-driven tumor penetration via EMT and FMT inhibition in the tumor microenvironment. ESMO Congress 2025; October 17-21, 2025; Berlin, Germany. Poster 269eP. 6. Hernando-Calvo A, Carvajal RD, Paik PK, et al. Phase I clinical trial of the bifunctional EGFR/TGF-β fusion protein ficerafusp alfa (BCA101) alone and in combination with pembrolizumab for advanced solid tumors. Clin Cancer Res. 2025;31(22):4623-4632. doi:10.1158/1078-0432.CCR-25-0100 7. Jung AR, Jung C-H, Noh JK, Lee YC, Eun Y-G. Epithelial-mesenchymal transition gene signature is associated with prognosis and tumor microenvironment in head and neck squamous cell carcinoma. Sci Rep. 2020;10:3652. doi:10.1038/s41598-020-60707-x 8. Bredell MG, Ernst J, El-Kochairi I, Dahlem Y, Ikenberg K, Schumann DM. Current relevance of hypoxia in head and neck cancer. Oncotarget. 2016;7(31):50781-50804. doi:10.18632/oncotarget.9549