Exploiting genomic vulnerabilities in lung cancer for therapeutic targeting

BJMO - volume 17, issue 4, june 2023

P. Giron PhD, J. De Grève MD, PhD


(Belg J Med Oncol 2023;17(4):132–4)


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Simply the B(r)east: Endothelial cell heterogeneity in health and disease

BJMO - volume 17, issue 3, may 2023

V. Geldhof MD, PhD


This thesis aimed to unveil new insights into breast cancer (BC) vasculature, since this could potentially have a large clinical impact. To do so, single-cell RNA-sequencing was performed on the breast cancer vasculature and tumour microenvironment. The analysis revealed novel interactions between immune cells and endothelial cells (ECs), and identified a capillary EC subtype, called lipid processing ECs (LIPECs), expressing genes regulated by PPAR-γ. Retrospectively, this study uncovered breast cancer-specific clinical benefits of PPAR-γ agonist (metformin) treatment, positively correlated with LIPEC abundance. In conclusion, these findings unravelled heterogeneity in breast ECs, and raise the question of whether targeting specific EC subtypes is a potential avenue for BC treatment.

(Belg J Med Oncol 2023;17(3):88–90)

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Immune cell and extracellular vesicle-based biomarkers for gynaecologic cancers

BJMO - volume 17, issue 2, march 2023

L. Lippens PhD, K. Vandecasteele MD, PhD, A. Hendrix PhD, H. Denys MD, PhD


Immune checkpoint blockade has shown great potential in oncology. However, only a fraction of patients benefits from this therapy. Furthermore, severe immune-related adverse events occur in a part of the patients, and financial toxicity cannot be underestimated. It is therefore important to develop predictive biomarkers to differentiate responders from non-responders. Tumour tissue samples offer a large amount of information as anti-tumour immunity is regulated through multiple factors in the tumour microenvironment. The potential of tumour-infiltrating immune cells was investigated to predict response to therapy and survival. In contrast to tissue biopsies, liquid biopsies allow for collection in a less invasive manner, allow for repetitive sampling during therapy, and offer information on all cancer cells in the tumour as well as metastases at distinct locations in the body. Extracellular vesicles (EVs) present in the circulation are a spatiotemporal fingerprint of the cell of origin. Therefore, EV-derived information has the potential to be used for diagnosis, prognosis, treatment selection and evaluating treatment response. However, the clinical application of EVs is currently hampered by a lack of sensitive, high-throughput and fast EV analysis techniques.

(BELG J MED ONCOL 2023;17(2):63–5)

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Patient selection strategies throughout the renal cell carcinoma disease spectrum

BJMO - volume 17, issue 1, january 2023

E. Roussel MD, PhD


The present doctoral thesis manuscript aims to inform disease prognosis and guide therapeutic decision-making at all stages of the renal cell carcinoma disease spectrum. Novel imaging methods to improve pre-surgical characterisation of renal masses were developed, as well as prediction models for the estimation of postoperative renal function. Next, four molecular subtypes of clear cell renal cell carcinoma were described, their underlying disease biology and their implications in both the localised and metastatic settings. Moreover, the potential candidates for cytoreductive surgery were described, as well as the morbidity accompanying such procedures in the metastatic setting.

(BELG J MED ONCOL 2023;17(1):31–2)

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Traveling the prostate cancer timeline in chase of treatment paradigms: Can we cure the incurable?

BJMO - volume 16, issue 7, november 2022

C. Berghen MD, PhD, S. Joniau MD, PhD, K. Rans MD, G. De Meerleer MD, PhD


When prostate cancer (PCa) patients are diagnosed as ‘incurable’, most patients still have many years to live and often undergo a continuum of burdensome and expensive systemic treatments that can impair quality of life. Due to the active promotion of new systemic therapies in the treatment of metastatic and/or castrationrefractory PCa patients, other treatment modalities such as modern radiotherapy (RT) have been considered as therapies that relieve symptoms, without offering any possibility of cure or additional quality of life-adjusted life years. This PhD thesis investigated whether the implementation of modern RT in previously non-RT indications could prove otherwise. To achieve this, the PCa timeline was followed in search of treatment paradigms, and re-introduced RT in different disease settings. Firstly, the addition of elective para-aortic lymph node radiotherapy was investigated in patients diagnosed with locally advanced pN1 prostate cancer, with local treatment of the prostate (bed) and pelvic lymph nodes, along with 24 months of ADT, in the prospective multicentric PART study. Secondly, a large retrospective study was performed, focused on patients with oligorecurrent prostate cancer who were treated with metastasis-directed therapy (MDT). Finally, the use of MDT was investigated in patients diagnosed with oligoprogressive metastatic castration-resistant prostate cancer (mCRPC), while continuing otherwise successful ongoing systemic treatment. Will this approach lead to a substantial postponement of next-line systemic treatment (NEST)?

(BELG J MED ONCOL 2022;16(7):363–6)

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Role and usefulness of an outpatient clinic for patients on oral anticancer therapy: 5-year experience in a general hospital in Belgium and review of the literature

BJMO - volume 16, issue 3, may 2022

N. Kizilmese PharmD, M. Baert PharmD, S. Thevelin PhD, PharmD, K. Eeckhaut MSN , T. Hendrickx PharmD


Oral anticancer therapy (OACT) is increasingly used for the treatment of cancer patients in the outpatient setting. Even for outpatients, clinical pharmacists (CPs) can provide in-depth patient education to ensure correct medication intake and effective management of adverse drug events (ADEs). It is currently unclear if this type of medication counselling can improve the care of outpatients on OACT. In 2010, a multidisciplinary outpatient clinic for patients on OACT (Raadpleging voor patiënten op Orale antitumorale Therapie Sint-Lucas, ROTS) was initiated at Sint-Lucas general hospital in Belgium. The ROTS outpatient service focuses on providing specialised counselling, support, and follow-up (by visit, phone, or mail) to provide a costeffective therapy and improve patients’ adherence in close collaboration with all healthcare providers (HPs). The CPs provided different interventions in the outpatient clinic. This report aims to evaluate the role and usefulness of this outpatient service. Specific objectives included a) number and type of interventions to assure safe, effective and cost-effective drug therapy, b) survey for adherence and satisfaction about counselling for patients, and c) satisfaction survey for physicians about the collaboration. Over a first five year period, a total of 2,974 interventions were performed on 181 patients, mainly consisting of ADE assessment and management, medication reconciliation and review, and adherence review and reinforcement, mostly by direct contact with the patients or remote via e-mail or telephone. In a recent survey, patients and HPs perceived these interventions as very useful, and the satisfaction rate about the provided information and ADEs management was high. In conclusion, our approach to setting up an outpatient service is well accepted by patients and HPs, showing the feasibility of integrating clinical pharmacy services in the multidisciplinary approach to the treatment of cancer patients.

(BELG J MED ONCOL 2022;16(3):133–41)

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Paving the way for immunotherapy in pancreatic cancer by exploring a novel combination immunotherapy consisting of a CD40 agonist and interleukin-15

BJMO - volume 15, issue 3, may 2021

J.R.M. Van Audenaerde PhD, G. Roeyen MD, PhD, M. Peeters MD, PhD, E.L.J.M Smits PhD


Pancreatic Ductal Adenocarcinoma (PDAC) has the worst 5-year survival of all cancer types. Treatment options for these patients are limited and consist mainly of chemotherapy. However, the unique tumour microenvironment with its dense, fibrotic shield causes resistance to current and novel therapies. Tackling this stromal shield is therefore deemed crucial for making progress in PDAC treatment. We investigated in this thesis the potential of Natural Killer (NK) cells to address this high medical need. Firstly, our systematic review revealed strong evidence of their importance in PDAC and how the tumour renders them into a suppressed and less functional state. Based on this information, we sought to stimulate NK cells in such way that they attack both tumour and surrounding stroma. We show that, upon stimulation with IL-15, NK cells are capable of killing both pancreatic cancer and stellate cells, the drivers of the stromal reaction, in a contact-dependant manner. Increased expression of NKG2D and TIM-3 receptors was partially responsible for this enhanced killing. Furthermore, in our search to potentiate IL-15 stimulation, we combined this with an immune priming CD40 agonist and demonstrated profound anti-tumour effects and prolonged survival in PDAC mouse models. Increased intra-tumoral cytotoxic T cells, NK cells and reduced T regulatory cells combined with increased cross-presenting dendritic cells in the tumour draining lymph nodes are the main effectors of the observed anti-tumour effects. Summarised, our data provide a strong rationale for NK cell-driven cancer immunotherapy where immune stimulation is combined with immune priming. Initiation of an early-phase clinical trials with this novel combination immunotherapy for PDAC patients is warranted.

BELG J MED ONCOL 2021;15(3):128-31

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