2023-07-26 14:31:59
“In this study we have identified the maximum tolerated dose and the recommended dose for a phase II trial. Regarding safety, it has been shown manageable toxicity dose dependent and preliminary antitumor activity has been observed especially in patients with salivary gland tumors” explain it Irene Branahead of the Head and Neck Tumors Group of the VHIOy of the UITM-CaixaResearch of the VHIOmedical oncologist at Vall d’Hebron University Hospital who led the study.
What is epigenetics?
«To understand what epigenetics is, we could say that genes are the ingredients of a recipe and the epigenetic marks would be the recipe instructions: what ingredients to use, in what proportion…» explains the Maria Vieitoresearcher of the VHIO Head and Neck Tumors Group and of the UITM-CaixaResearch of the VHIO, medical oncologist of the Vall d’Hebron University Hospital.
the drug JNJ-64619178developed by the pharmaceutical Janssen Research & Developmentis a very potent and selective inhibitor of the PRMT5 protein involved in the binding of epigenetic marks to the DNA sequence.
«PRMT5 plays a regulatory role in the progression of human cancers since it activates the expression of genes associated with the proliferation, invasion and migration of cancer cells as a switch and its overexpression is an indicator of poor prognosis in many types of human cancer » explains Vieito.
“Recent studies have shown that PRMT5 inhibition has antitumor effects in preclinical models of various types of tumors. Therefore, the inhibition of PRMT5 is an attractive clinical target for the treatment of malignant tumors”, adds la Braña.
First human clinical study
The Molecular Cancer Therapy Research Unit (UITM) – CaixaResearch, directed by Elena Garralda, has led the first human clinical trial of this drug. In the study participated ninety patients with various types of solid tumors advanced patients who had received an average of three lines of systemic therapy. The most common tumor types were adenoid cystic carcinoma (28.9%), pancreatic cancer (14.4%), prostate cancer (13.3%), and uveal melanoma (8.9%). All received the drug JNJ-64619178.
Regarding safety, the most frequent adverse effects were hematological and gastrointestinal and they presented greater frequency and severity with increasing dose. The drug was well tolerated above tolerability that present other drugs with an epigenetic mechanism.
Antitumor activity in patients with adenoid cystic carcinoma
“JNJ-64619178 demonstrated preliminary antitumor activity especially in patients with adenoid cystic carcinoma” he states Vladimir Galvaoresearcher of the UITM-CaixaResearch and co-author of the study. “This is a rare tumor of the salivary glands that is resistant to chemotherapy, so we currently do not have an effective treatment for these patients.”
The case of a patient with a rare pancreatic cancer who had not responded to previous treatments stands out and who, since the start of the trial four years ago, keeps disease under control.
“The results of this trial point to the need for further research in the biomarker identification for the selection of patients who could benefit from a treatment based on PRMT5 inhibition» concludes Irene Braña.
Translational research model
One of the main lines of research of the VHIO Head and Neck Tumors Group is the development of epigenetic drugs capable of turn off genes involved in cancer development. The group works closely with the Cancer Molecular Therapy Research Unit (UITM) – CaixaResearch which is financed by the «la Caixa» Foundation and that allows the development of a truly translational research model with the aim of bringing scientific knowledge closer to clinical practice.
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