Dr Ali A Suwaidan
About
Biography
Dr Ali Suwaidan is a Consultant Medical Oncologist at the Royal Surrey NHS Foundation Trust and currently serves as Divisional Research Lead for Oncology. He is an Honorary Clinical Senior Lecturer at the University of Surrey. His specialist interests include the management of thoracic malignancies, hepatopancreatobiliary cancers (including liver, pancreatic, biliary tract and gallbladder cancers), and neuroendocrine tumours and carcinomas.
Dr Suwaidan completed his training in Internal Medicine and Medical Oncology at leading UK institutions, including University Hospitals of Leicester NHS Trust and the Royal Marsden NHS Foundation Trust. Alongside his clinical practice, he has an established academic and research background in translational and clinical research. He completed a Master’s degree at the University of Leicester and doctoral research at King’s College London, where his work focused on targeting DNA damage response pathways to enhance anti-cancer immune responses.
His research has been supported by prestigious national funding bodies, including Cancer Research UK and the National Institute for Health and Care Research (NIHR), and has led to multiple national and international awards. These include the European Society for Medical Oncology (ESMO) Merit Award and the RCSI Alumni Inspiring Excellence Award, recognising his contributions to cancer research, innovation, and medical education.
Publications
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most hard to treat malignancies, characterised by significant immune evasion and resistance to current systemic agents. Despite substantial progress in understanding tumour immunology across other cancer types, PDAC continues to exemplify an immunologically "cold" tumour, where a desmoplastic stroma, inadequate T-cell infiltration, and complex immunosuppressive networks combine to impede effective anti-cancer immunity. This review summarises current knowledge on the mechanisms underlying immune escape in PDAC, including aberrant antigen presentation, stromal–immune crosstalk, recruitment of regulatory T cells and myeloid-derived suppressor cells, and the metabolic and hypoxic constraints imposed by the tumour microenvironment. We also discuss recent advances in preclinical and clinical studies aiming to overcome these barriers, ranging from stromal modulation and targeting immune checkpoints to integrating radiotherapy, chemotherapy, and DNA damage response modulation to enhance immunogenicity. Special emphasis is placed on the emerging concept of therapeutic replication stress and its potential to induce immunogenic cell death and reshape the tumour immune landscape. We outline the mechanistic basis for treatment resistance of PDAC and discuss strategies to convert the malignancy from an immune-resistant to an immune-responsive state.
Background
The IMbrave150 trial established atezolizumab plus bevacizumab (ATE/BEV) as a first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC), demonstrating improved overall survival (OS) and progression-free survival (PFS) over sorafenib. Ongoing real-world data collection are needed to assess ATE/BEV effectiveness and safety.
Methods
Retrospective data were collected from 3 oncology centres in the Midlands, UK, with local audit committee approval. Eligible patients were required to have a diagnosis of HCC confirmed by histological biopsy wherever feasible.
Results
As of August 2025, 332 patients were included in analysis, with a median time to follow-up of 12 months [95% CI: 10.1 – NA]. The median OS was 16.5 months [95% CI: 14.2 – 20.7], with a 6-month OS of 76.8% [95% CI: 71.6 – 82.5]. The median PFS was 12.3 months [95% CI: 10 – 16.3], with a 6-month progression-free survival of 70.8% (95% CI: 64.6 - 77.6). The objective response rate (ORR) was 42.9%, with 100 partial or complete responses (95% CI: 42.5% - 56.1%). 190 of 233 (81.54%) patients discontinued the treatment at time of analysis, with a median time to discontinuation of 6.5 months (95% CI: 5.9 – 8.3 months). Reasons for discontinuation included progression (47.4%), toxicity (22.6%) and liver decompensation (17.9%). 91 of 233 (39.06%) patients received a second-line therapy after stopping ATE/BEV. Adverse events of any grade occurred in 96 patients (41.2%); 54 patients (23.2%) had ≥ grade 3 toxicity that warranted treatment cessation of combination ATE/BEV. 74 patients (31.8%) experienced ATE-related adverse event, all grade 2 or above. 26 patients (11.2%) experienced a BEV-related toxicity ≥ grade 3 toxicity. Within, we report the spectrum of presentations related to toxicity from each treatment.
Conclusions
In this real-world multicentre UK cohort, ATE/BEV demonstrated survival outcomes comparable to IMBrave 150 trial data, with manageable toxicity and a substantial proportion of patients proceeding to second-line therapy. These findings support the robustness of ATE/BEV as first-line standard of care in unresectable HCC beyond clinical trial settings.
Background
HCC is the most common primary liver cancer and a major cause of cancer deaths globally. In the UK, its rising incidence (∼7,500 cases/year) is linked to increasing chronic liver disease. Advances in systemic therapies, including targeted agents and immunotherapy, have improved outcomes, but real-world data on treatment patterns and outcomes remain limited.
Methods
This retrospective cohort study included adults with histologically or clinically diagnosed HCC who received systemic therapy between January 2019 and June 2024. Patients were identified via electronic records and ChemoCare at University Hospitals of Leicester NHS Trust. Data on demographics, liver function (Child-Pugh), tumour stage (BCLC), treatment regimens, and outcomes (time to discontinuation [TTD], progression-free survival [PFS], overall survival [OS]) were analysed using descriptive and Kaplan-Meier statistics.
Results
Among 102 HCC patients, 42 received primary systemic anti-cancer therapy (SACT), while 60 underwent trans-arterial chemoembolization (TACE). 17 TACE patients later received SACT, with 13 treated in Leicester, bringing the total SACT cohort to 55. The median age was 69.3 years (range 47.4–88.7), with 88.9% male. Most had ECOG 0–1 (87%) and well-preserved liver function (79.6% Child-Pugh A). Advanced disease was common (57% BCLC C, 30% B, 13% A). First-line treatments included sorafenib (51.8%), atezolizumab-bevacizumab (31.5%), and lenvatinib (16.7%). Atezolizumab-bevacizumab had the highest response (35%) and disease control rates (76.5%), with the longest TTD (162 days) vs. lenvatinib (138 days) and sorafenib (57 days). Survival outcomes favuored atezolizumab-bevacizumab, with median PFS of 8.6 months vs. 5.0 (lenvatinib) and 2.8 (sorafenib) (p < 0.001). Median OS was longest for atezolizumab-bevacizumab (16.6 months) vs. lenvatinib (6.7) and sorafenib (6.4) (p = 0.0011).
Conclusions
This real-world study highlights variability in HCC treatment outcomes. Atezolizumab-bevacizumab demonstrated superior efficacy, aligning with IMbrave150 study findings. These results support integrating and sequencing newer therapies in clinical practice.
Background: In advanced head and neck squamous cell carcinoma (HNSCC), immune checkpoint inhibitors are only effective in 15-20% of cases. Defects in replication stress response represent a promising avenue for enhancing the therapeutic efficacy of immunotherapy through DNA damage and the release of immunostimulatory DNA. MUS81, a DNA structure-specific endonuclease involved in resolving replication stress, is upregulated in many cancer types including HNSCC, and MUS81-associated cytosolic DNA is implicated in triggering cGAS-STING mediated innate immunity. The objectives of this study were to assess the impact of targeting MUS81 on HNSCC cell sensitivity to cisplatin, and investigate its role in enhancing immunotherapy response in HNSCC, through the cell viability and cell cycle analysis, differential gene expression, and DNA release within small extracellular vesicles (exosomes).
Methods and Results: We used HNSCC cell lines and patient-derived organoids (PDOs) to investigate the consequences of CRISPR/Cas9-mediated MUS81 knockout (KO). We demonstrated that MUS81 KO increased HNSCC cell sensitivity to cisplatin, inducing a G2/M cell cycle arrest. Transcriptomic analysis of differentially expressed genes (DEG) in MUS81 KO vs control cells highlighted upregulation of ANXA6 (tumor suppressor gene encoding for Annexin A6), MACROH2A2 (involved in the quiescent phenotype acquisition of malignant HNSCC cells) and CDA (encoding for cytidine deaminase, implicated in replication stress). MUS81 KO was also associated with downregulation of LCP1 (encoding for lymphocyte cytosolic protein 1, upregulated in oral cancer and controlling cellular proliferation, invasiveness, and migratory activities). Gene Set Enrichment Analysis (GSEA) of RNA-seq data, revealed positive enrichment in MUS81 KO cells treated with cisplatin in genes involved in the hallmark interferon alpha (Normalized Enrichment Score (NES) 3.03, p-value < 0.001) and interferon gamma (NES 2.83, p- value < 0.001) pathways, indicative of innate and adaptive immune responses. Additionally, the pathway of hallmark inflammatory response was positively enriched (NES 2.22, p < 0.001). In addition, cisplatin treatment in MUS81 KO was associated with notable alterations in the concentration and length of exosomal DNA, with implications for immune response modulation within the tumor microenvironment.
Conclusions: Our study underscores the potential significance of MUS81 as a novel therapeutic target in HNSCC. In addition to sensitizing HNSCC cells to chemotherapeutic agents, targeting MUS81 may influence the dynamics of the tumor microenvironment, thereby enhancing the prospects of immunotherapy in this context. Further in-depth investigations are imperative to validate these observations and facilitate the development of innovative therapeutic strategies tailored to targeting MUS81 in HNSCC.
hioredoxin-interacting protein (TXNIP) is commonly considered a master regulator of cellular oxidation, regulating the expression and function of Thioredoxin (Trx). Recent work has identified that TXNIP has a far wider range of additional roles: from regulating glucose and lipid metabolism, to cell cycle arrest and inflammation. Its expression is increased by stressors commonly found in neoplastic cells and the wider tumor microenvironment (TME), and, as such, TXNIP has been extensively studied in cancers. In this review, we evaluate the current literature regarding the regulation and the function of TXNIP, highlighting its emerging role in modulating signaling between different cell types within the TME. We then assess current and future translational opportunities and the associated challenges in this area. An improved understanding of the functions and mechanisms of TXNIP in cancers may enhance its suitability as a therapeutic target.
Introduction
Patients with gastrointestinal (GI) cancers have an increased risk of serious complications and death from SARS-CoV-2 infection. The immunogenicity of vaccines in patients with GI cancers receiving anti-cancer therapies is unclear. We conducted a prospective study to evaluate the prevalence of neutralizing antibodies in a cohort of GI cancer patients receiving chemotherapy following SARS-CoV-2 vaccination.
Materials and Methods
Between September 2020 and April 2021, patients with cancer undergoing chemotherapy were enrolled. At baseline (day 0), days 28, 56, and 84, we assessed serum antibodies to SARS-CoV-2 spike (anti-S) and anti-nucleocapsid (anti-NP) and concomitantly assessed virus neutralization using a pseudovirus neutralization assay. Patients received either the Pfizer/BioNTech BNT162b2, or the Oxford/AstraZeneca ChAdOx1 vaccine.
Results
All 152 patients enrolled had a prior diagnosis of cancer; colorectal (n = 80, 52.6%), oesophagogastric (n = 38, 25.0%), and hepato pancreatic biliary (n = 22, 12.5%). Nearly all were receiving systemic anti-cancer therapy (99.3%). Of the 51 patients who did not receive a vaccination prior to, or during the study, 5 patients had detectable anti-NP antibodies. Ninety-nine patients received at least one dose of vaccine prior to, or during the study. Within 19 days following the first dose of vaccine, 30.0% had anti-S detected in serum which increased to 70.2% at days 20-39. In the 19 days following a second dose, anti-S positivity was 84.2% (32/38). However, pseudovirus neutralization titers (pVNT80) decreased from days 20 to 39.
Conclusion
Despite the immunosuppressive effects of chemotherapy, 2 doses of SARS-CoV-2 vaccines are able to elicit a protective immune response in patients’ ongoing treatment for gastrointestinal cancers. Decreases in pseudoviral neutralization were observed after 20-39 days, re-affirming the current recommendation for vaccine booster doses.
Clinical Trial Registration Number
NCT04427280.