Enzyme-targeting drug stops tumour growth in multiple cancers

Researchers at the Peter MacCallum Cancer Centre have used a pioneering new drug to control the growth of tumours and overcome existing drug resistance in multiple cancer types, publishing their results in the journal Cancer Discovery.

An enzyme critically associated with tumour growth, called cyclin-dependent kinase 2 (CDK2), has long been a target for researchers but it has been incredibly difficult to create a therapeutic drug that can successfully inhibit it. The new research describes a potent and selective CDK2 inhibitor called INX-315, developed by US-based company Incyclix Bio, which has shown control of tumour growth in two groups of cancer in preclinical models.

INX-315 works in a group of cancers with amplification of the CCNE1 gene, which comprises a variety of cancers including some ovarian, gastro-oesophageal and uterine cancers. The amplification of this gene is linked to an increase in CDK2 activity. INX-315 inhibits CDK2 and blocks aberrant cell proliferation, which causes the growth of these tumours.

“Our study shows, for the first time, that inhibiting CDK2 pharmacologically is a very promising strategy,” said Peter Mac’s Associate Professor Shom Goel, senior author of the study.

“We are excited by this research because these cancer types with amplification of the CCNE1 gene generally carry a poor prognosis and are notoriously unresponsive to current therapies.”

Additionally, the drug works in breast cancers that have acquired resistance to CDK4/6 inhibitors, which are used to treat many patients with metastatic breast cancer. INX-315 can overcome this resistance, also stopping cancer cell division.

“Breast cancers often develop resistance to CDK4/6 inhibitors over time; however, in our study, we show that this resistance can be driven by CDK2, and that INX-315 works to combat this,” Goel said.

“The research also sheds light on important questions related to cell cycle biology and drug resistance in cancer, and is the first published paper describing the effects of a CDK2 inhibitor in cancer.”

Co-senior author Patrick Roberts, the CEO of Incyclix Bio, described CDK2 as “a critical target in oncology with broad clinical potential across multiple cancer types, including treatment-resistant cancers”. With INX-315 now entering clinical development with a first-in-human trial led by a Peter Mac clinician researcher, Roberts said he is excited to bring a new therapeutic option to patients with difficult-to-treat cancer.

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