Mechanism of interactions between dietary isothiocyanates and anti-cancer drugs in triple negative breast cancer (BAOY_U26MEDCPRT)
Key Details
- Application deadline
- 5 October 2025 (midnight UK time)
- Location
- UEA
- Funding type
- Directly Funded (Home and International)
- Start date
- 1 February 2026
- Mode of study
- Full-time
- Programme type
- PhD
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Project description
Primary supervisor - Prof Yongping Bao
High consumption of cruciferous vegetables can reduce the risk of cancer. This protection has been attributed to isothiocyanates (ITCs) in such vegetables. However, isothiocyanates have been shown to possess hormetic effects (stimulation at low doses and inhibition at high doses) on cell growth. We have shown that high doses of isothiocyanates have anti-cancer effects on cell migration, invasion and angiogenesis. Interestingly, there are synergistic interactions between ITCs and anticancer drugs such as sorafenib and dasatinib (1,2).
Breast cancer is one of the most common malignancies in women. Particularly, triple negative breast cancer (TNBC) has a high rate of recurrence and is more challenging to treat due to the absence of oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. Therefore, TNBC is characterised by aggressive clinical behaviour, and inherent resistance to conventional chemotherapy. Recently, combinational therapy has become a cornerstone in cancer treatment to potentiate therapeutic effectiveness and overcome drug resistance and metastasis. For example, sorafenib, a novel multi-kinase inhibitor, is broadly used alone or in combination with other therapeutics to combat breast cancer (3). We have also shown a dietary ITC called sulforaphane (SFN) potentiates the efficacy of cisplatin (CDDP) against breast cancer in animal models (4).
In this PhD project, we will investigate:
The effect of combined treatment with ITCs and a selected anti-cancer drug (sorafenib or triptolide) on breast cancer will be studied using MDA-MB-231 and MCF-7 breast cancer cells, and a normal breast cell line MCF-10A. Cell viability assays, colony formation, and flow cytometry analysis will be used to assess the anti-cancer effects. The combination index will be calculated, and the selected pair of drugs which have synergy will be further studied.
Effects on cell migration, invasion, angiogenesis, and tumour microenvironment (TME) will be studied using a range of assays established in-house. The effects of drugs given alone will be compared with combined treatments.
Molecular mechanisms of interactions between ITCs and anti-cancer drugs in cancer therapy will be investigated. Antibody arrays, qRT-PCR, Western blotting assays and RNA sequencing (RNA-seq) will be employed to study the underlying mechanism of action.
Finally, a mouse xenograft model will be employed to assess the efficacy of the combinations of ITCs and anti-cancer drugs on cancer therapy.
A combination of ITCs and anti-cancer drugs could enhance cancer treatment efficacy and reduce toxicity or overcome chemoresistance, and improve understanding of the mechanism of bioactive phytochemicals in prevention and treatment of cancer (5). This study will provide useful information for a further clinical trial using combined therapy. Ultimately, the translational potential of these findings could markedly improve public health outcomes and quality of life, particularly for populations at high risk for this aggressive and treatment-resistant breast cancer subtype.
Entry requirements
The minimum entry requirement is 2:1. in Biological sciences; cell & molecular biology, oncology, biomedicine.
Funding
This project is jointly funded for three years by the Cancer Prevention Research Trust. Funding includes tuition fees at Home-fee rate, an annual stipend for maintenance starting at £20,780 in the academic year 2025/26, and £1,000 per annum to support research training.
Overseas applicants may apply but they are required to self-fund the difference in fee rates. Please see View Website for details of Home and International tuition fees.
References
Strusi G, Suelzu CM, Horwood N, Münsterberg AE, Bao Y. Phenethyl isothiocyanate and dasatinib combination synergistically reduces hepatocellular carcinoma growth via cell cycle arrest and oxeiptosi. In: Frontiers in Pharmacology, 2023 Oct 4:14:1264032. doi: 10.3389/fphar.2023.1264032
Strusi G, Suelzu CM, Weldon S, Giffin G, Münsterberg AE, Bao Y. Combination of phenethyl isothiocyanate and dasatinib inhibits hepatocellular carcinoma metastatic potential through FAK/STAT3/cadherin signalling and reduction of VEGF secretion, Pharmaceutics 2023, 15(10), 2390; https://doi.org/10.3390/pharmaceutics15102390
Wang Q, Cheng N, Wang W, and Bao Y. Synergistic action of benzyl Isothiocyanate and sorafenib in a nanoparticle delivery system for enhanced triple-negative breast cancer treatment. Cancers 2024; 16(9), 1695; https://doi.org/10.3390/cancers16091695
Xu Y, Han X, Li Y, Min H, Zhao X, Zhang Y, Qi Y, Shi Y, Qi S, Bao Y, Nie G. Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity. ACS Nano, 2019;13(11):13445-13455. doi:10.1021/acsnano.9b07032
Wang Q, Li D, Liu L, Shan Y, and Bao Y. Dietary isothiocyanates and anticancer agents: exploring synergism for improved cancer management. in Frontiers in Nutrition. 2024; 11:1386083. doi:10.3389/fnut.2024.1386083.