Joanne Siwan, co-director of the Preclinical and Translational Research Program at the Vall d’Hebronne Oncology Institute (VHIO).
According to recent statistics, the malignant melanoma is the main cause of death by skin cancer, more than 57,000 estimated deaths in 2020 all over the world. Given the increasing incidence of skin cancer, the need to develop more effective and specific treatments to improve outcomes for these patients is of paramount importance.
Publish an investigation in cancer research Directed by Joan SiwanCo-Director of the Preclinical and Translational Research Program at Val d’Hebron Oncology Institute (VHIO), with the support of the Spanish Association Against Cancer, has proven the efficacy of C1aa potent BRAF inhibitor that can cross the blood-brain barrier and penetrate the brain, achieving better results in preclinical models of the drugs currently in use, so it can become Effective course of treatment For patients with BRAF V600E/K metastatic melanoma.
“Our investigations showed surprising activity in Metastatic brain models. C1a achieved more effective exposure to the cerebral chamber and superior results compared to Other BRAF inhibitors. Our results have supported clinical validation of this new agent in setting up current treatments, and patients are already being recruited for a clinical trial that will test this compound. The positive result from the trial could provide a therapeutic alternative for patients with brain metastasis,” adds Joanne Siwan, Icrea Research Professor and Co-Director of the VHIO Preclinical and Transformational Research Program.
Tumors eventually become resistant Targeted therapies. In response to this predicted phenomenon, researchers also studied resistance mechanisms To help prevent a tumor from escaping the action of C1a, try to identify a Possible combination therapy strategy To prolong anti-tumor responses.
The immune system is involved in fighting tumors
Analysis of tumors that recurred after treatment with C1a showed that Reactivate MAPK It is the main mechanism of resistance in both peripheral and metastatic brain settings and that BRAF kinase domain replication is the dominant factor in resistance.
“These contributions will help Identify vital signs of response to treatment and, ultimately, to guide patient stratification in clinical trials,” says Esther Bonneville-Texdor, first co-author of this study and a member of the Gene Expression and Cancer Group at VHIO, led by Joanne Siwan.
In order to identify the mechanisms involved in C1a resistance, a text analysis subordinate resistant tumors An inflammatory phenotype was observed, indicating a clear effect on the immune system. Given that immune checkpoint inhibitors (ICIs) are already used clinically to treat melanoma, researchers discovered a combined approach with C1a and anti-PD1 antibodies.
The results showed that C1a also enhances Strong anti-tumor responses When combined with a PD1 antagonist, it significantly reduces Appearance of repetitions and resistance to C1a treatment. Therefore, the therapeutic combination of C1a with Blockade of immune checkpoints It can give new hope to this category of patients.
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