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Heligenics has launched a precision test to select among three commonly used drugs for HER2 positive breast cancer tumors: Tykerb (GSK’s laptinab), Nerlynx (Puma Biotechnology’s neratinib), and Tukysa (Seagen’s tucatinib).

The test is based on Heligenic’s proprietary GigaAssay technology, which “produces mutation/function maps of all mutations,” the company reports. The test can currently be used to determine which of these three therapies, alone or in combination, are most likely to work in patients with human epidermal growth factor receptor 2 (HER2) positive tumors. It also tells whether the tumor is resistant to one or all.

“This test is a great example of the future of personalized drug therapy,” said Jerome Rotter, a board member of Heligenics and Director of Translational Genomics and Population Sciences at the Lundquist Institute / Harbor-UCLA.

The World Health Organization reports that in 2020, there were 2.3 million women diagnosed with breast cancer and 685 000 deaths globally. As of the end of 2020, there were 7.8 million women alive who were diagnosed with breast cancer in the past five years, making it the world’s most prevalent cancer. Up to 20 percent of women with breast cancer have tumors with high levels of HER2.

Multiple drugs are available to treat breast cancer, however most patients eventually become drug resistant and there is no systematic approach to identifying the variants that cause target-derived drug resistance.

Heligenics says its GigaAssay technology can rapidly determine which of the 10,000s of possible mutants would make a breast cancer patient’s tumor susceptible to a particular drug. The test also identifies which of these variants produce resistance. The company’s aim, according to their press release, is to “transform analysis of biopsies to create a data-driven approach to treatment.”

The GigaAssay is a massively parallelized platform for assaying molecular functions of single cells in culture without the need for mechanical separation of the cells.  It was developed at the University of Nevada Las Vegas in the Schiller Laboratory of Applied Bioinformatics.

It was originally developed to provide an accurate, high-throughput functional assay of transcriptional activity of Tat mutants in human cells for HIV research. Tat enhances HIV-1 replication.

In that study, each cell was infected with one virus from a library encoding thousands of Tat mutant proteins, with each viral particle encoding a random unique molecular identifier. The team demonstrated proof of concept by measuring transcription of a GFP reporter in an engineered reporter cell line driven by binding of the HIV Tat transcription factor to the HIV long terminal repeat.

The company has now expanded its work to breast cancer, with the test for response to these three drugs.

In their paper about the Tat work, the team writes “Although many high-throughput screens have been developed, there is no platform to broadly assesses molecular functions and cell processes in the context of human or mammalian cells.”

They add that, “Most high-throughput technologies identify cellular components such as DNA, RNA, or protein species, and some assess intermolecular interactions. CRISPR/Cas9 and RNAi genome-wide screens identify genes necessary for cellular or organismal processes. Pathways and networks are often predicted from the resulting data, but these experiments only indicate a role for a gene, and do not conclusively assess mechanisms of action.”

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