I’m Fabrizio Fai, a PhD student at the Queen Mary University of London. At the time of writing this blog post, I am working at the Barts Cancer Institute in the Translational Cancer Metabolism (TCM) lab led by Dr Barrie Peck (https://www.bartscancer.london/staff/dr-barrie-peck/) and I am in my third and final year of PhD.
I was one of the attendees of the 2023 BACR-organized Conference “Trailblazers in Cancer Research: The Next Generation” where I won the best Poster Award!
I am always excited to participate in scientific communication events such as talks organized by and in my institute and conferences. This year's BACR conference was an amazing occasion where I was able to share some insights into my PhD project. It was held in a very central area of Manchester, easily accessible for people like me who came earlier in the day from London to attend the event. The Pendulum Hotel was a warm and welcoming venue, and the BACR staff ensured we had everything we needed to enjoy the experience. You can see a super smiley picture of me as a winner and read more about it in the paper that summarises the meeting in Biology Open (https://journals.biologists.com/bio/article/12/10/bio060121/333524/Trailblazers-in-cancer-research-the-next).
Personally, I thoroughly enjoyed interacting with people coming from different parts of the UK and exchanging personal experiences talking about academia, especially being at the soon end-point of my student career and asking for advice from more senior post-docs.
Since I have won for my poster presenting skills, I will try my best to keep this as short as a 3-minute pitch as I would do by explaining it in person!
I have started my PhD project stemming from a previous publication of my supervisor (https://pubmed.ncbi.nlm.nih.gov/27042297/), identifying the metabolic enzyme Stearoyl-CoA desaturase (SCD) as an appealing therapeutic target in breast and prostate cancer cells. SCD controls the first committed desaturation step in lipogenesis, a pathway vastly documented to be up-regulated in many cancers, among them the hormone-independent Triple Negative Breast cancers (TNBCs). Currently, there are no known and robust biomarkers that impart or predict sensitivity to SCD inhibition. Therefore, my project within the frame of the state-of-art literature was to discover and study possible biomarkers related to targeting SCD in TNBCs. Our findings indicate that the lipid transporter CD36 is lost in a small but significant proportion of human breast cancers and that SCD expression is significantly upregulated in these tumours. We used a pair of CRISPR-Cas9-engineered HAP1 cell lines to investigate how CD36 affects SCD expression and its inhibition. Interestingly, these cells are haploid and therefore represent a useful tool to explore the dichotomy between the presence/absence of the lipid transporter. We observed that CD36 loss imparted sensitivity to SCD inhibition (the small molecule inhibitor A939572 has been used), and this was especially evident in lipid-replete conditions. Furthermore, a small panel of six TNBC cell lines with a copy number gradient of CD36, ranging from one up to six, were also tested. In a similar manner, an inverse correlation between CD36 and SCD sensitivity was observed. Moreover, we demonstrated that this sensitivity was rescued by reinstating intracellular Monounsaturated Fatty Acids (MUFAs) levels via a CD36-independent mechanism. These represent the class of molecules that would be synthesized by SCD enzymatic reaction (in particular palmitoleate and oleate) and also a substrate of the lipid transporter CD36. Thus, SCD inhibition is effective in CD36-low cell lines and this is due to the deficiency of MUFAs. In conclusion, we have found that CD36 loss results in increased SCD activity and response to SCD inhibition in cancer cells. As SCD-targeted therapies enter clinical testing, for example, SSI-4 (Modulation Therapeutics), this study could provide the necessary tools and patient stratification rationale for validating CD36 loss as a biomarker for SCD inhibitors response in human TN
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