Biomarkers Of Response To Cyclin D - CDK4/6 Targeted Therapies In Human Cancers

Separation of cancer patients in different subgroups based on these biomarkers will allow personalized treatment, which will save time, money and improve treatment efficacy.These markers provide inclusion/exclusion criteria for clinical trials, which will save time, money and increase success rate.

Cancer specimens from individual patients can be tested for the alterations in the relevant predictive biomarkers of sensitivity/resistance via several techniques such as SNP arrays, southern blot analysis, RNA sequencing, ELISA, and antibody-based methodology.  If alterations were found, these patients can be considered as appropriate or inappropriate candidates to receive CDK-4/6 inhibitor based therapies as a part of their treatment.  Clinical trials testing new CDK-4/6 inhibitors may use these sensitivity/resistance biomarkers as inclusion/exclusion criteria to maximize efficacy signal.

UCLA researchers have identified a list of genetic markers that have not previously been implicated in tumor susceptibility or resistance to CDK-4/6 inhibition.

20170067116

State Of Development

• 9 genetic response markers associated with sensitivity or resistance to CDK-4/6 inhibition are identified.  
• These biomarkers were analyzed in 12 different cancer types. The candidate biomarkers predictive of sensitivity were sufficiently frequent and associated with sensitivity in 6 of the 12 cancer histologies. The candidate biomarkers predictive of resistance were sufficiently frequent and associated with resistance in 6 of the 12 cancer histologies.  
• These biomarkers are in the pre-clinical, experimental phase and need functional validation and validation in clinical cohorts.

Background

Cancer is a leading cause of death worldwide and the number of new cases is expected to rise by 70% in the next 2 decades. Many cancers have a higher chance of cure if detected earlier and treated adequately. Because cancer describes a complex and heterogeneous group of diseases, standardized treatment across all patients has been proved to be ineffective. Instead, personalized medicine has emerged as an important tool in guiding treatment decisions.

Cyclin-dependent kinases (CDK) control cell cycle transition and have long been considered as promising targets for cancer therapies. However to date, several cdk inhibitors have been evaluated in cancer medicine without significant clinical activity. Clinical trials are currently underway with CDK-4/6 inhibitors and most have been designed as “biomarker independent”. As a result, these trials may show little or no efficacy compared to those enriched for patients with genomic biomarkers of susceptibility to CDK-4/6 inhibition.

Related Materials

von Euw E M, Conklin D, Rong H M, et al. Identification of markers of sensitivity and resistance to palbociclib (PD0332991) in melanoma[J]. Cancer Research, 2014, 74(19 Supplement): 1321-1321.

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Tech ID/UC Case

27272/2014-522-0

Related Cases

2014-522-0

USA

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