The synergy between alkylating agents and ERCC1-XPF inhibitors is p53 dependent.

Background: DNA repair plays a major role in maintaining genomic stability, thus limiting the transformation of normal cells into cancer cells. However, in cancer patients treated with DNA-targeting drugs, DNA repair can decrease efficacy by removing the damage generated by such molecules that is needed to induce pharmacological activity. Inhibiting DNA repair thus represents an interesting approach to potentiating the activity of chemotherapy in this setting.

Looking for the unexpected in purine and pyrimidine metabolism.

In June 2023, the Purine and Pyrimidine Society (PPS) organized the 20 biennial symposium on Purine and Pyrimidine metabolism (PP23). The symposium was organized in Los Angeles, California, USA, by Pr Caius Radu affiliated to UCLA. The scientific program covered various topics such as inborn errors, cancer, immunity, enzymatic reactions, drug development etc and was presented at 9 sessions over three days.

Clinical use of biomarkers in the field of cytotoxic nucleoside analogues.

Objectives: Cytotoxic nucleosides (gemcitabine, cytarabine…) are used for the treatment of various malignancies. Their activity is dependent on the interaction with several proteins and enzymes of nucleotide metabolism. It has for a long time been hypothesized that the clinical activity of nucleoside analogues can be predicted by studying corresponding genes or gene products in clinical samples.

A systemically administered detoxified TLR4 agonist displays potent antitumor activity and an acceptable tolerance profile in preclinical models.

Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for immunostimulation in cancer therapy. Although LPS possess anti-tumor activity, toxicity issues prevent their systemic administration at effective doses in humans. We first demonstrated that LPS formulated in liposomes preserved a potent antitumor activity upon systemic administration in syngeneic models, and significantly enhance the antitumor activity of the anti-CD20 antibody rituximab in mice xenografted with the human RL lymphoma model.