By Jonathan King, Cancer Center at Illinois
Estrogen receptor-positive breast cancer is the most common form of breast cancer, affecting approximately 75 percent of breast cancer patients. In advanced and metastatic form, it is lethal, claiming the lives of nearly 350,000 individuals annually. Presently, no drug is able to eradicate these advanced tumors.
Cancer Center at Illinois (CCIL) researchers Paul Hergenrother and David Shapiro are working to change that with the anticancer compound developed in their collaborative labs and now licensed for pre-clinical development.
The biotech company Oncoteq recently announced the licensing of the novel compound TEQ103 from Systems Oncology. TEQ103 is the product of the collaboration between CCIL researchers Hergenrother and Shapiro, who developed the molecules for the activation of anticipatory unfolded protein response (a-UPR), and Systems Oncology, who advanced the novel technology for clinical viability.
TEQ103 targets estrogen receptor alpha (ERα) positive breast cancer cells and kills only the cells with an activated stress response, the so-called a-UPR. “The a-UPR is already on in cancer cells and helps shield them from other anticancer drugs. Our compounds are unique in that they work by over-activating this pathway, switching into a lethal mode that kills the cancer cells.” Shapiro said. Presently, endocrine breast cancer treatments function by slowing tumor growth or modulating estrogen levels; however, the efficacy of current treatments falls short in eradicating advanced ERα-expressing breast cancers.
This compound emerging from the Hergenrother-Shapiro collaboration is their latest effort aimed at eradicating ERα-expressing breast cancer. As reported in 2020, Bayer AG licensed the breast cancer therapeutic ErSO for clinical development, which was born from Hergenrother and Shapiro’s cancer research. In 2021 and 2022, Hergenrother and Shapiro reported developments in two scientific papers, “A Small-Molecule Activator of the Unfolded Protein Response Eradicates Human Breast Tumors in Mice” in Science Translational Medicine and “Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer” in the Journal of Medicinal Chemistry.
The 2021 paper spoke of unprecedented tumor “eradication” in mouse models. “We’ve never seen a class of compounds that looks this good,” said Hergenrother. “It is really, really remarkable. This is a very promising compound for breast cancer treatment.”
Now in the hands of Oncoteq, this new compound will undergo pre-clinical drug development, with the goal of advancing the molecule to human clinical trials in late-stage metastatic breast cancer patients by 2025. “It’s great to find a partner in Systems Oncology, and now Oncoteq, that has the resources to take it all the way through to clinical trials,” explained Hergenrother.
“Metastatic breast cancer is still a major problem and needs much better treatments. I am thankful to work with great colleagues such as Professor Shapiro, and also Professors Tim Fan and Erik Nelson, to move these promising compounds forward to help patients. It’s a trailblazing experience, hopefully making it easier to advance the next technology coming out of the CCIL here at Illinois,” said Hergenrother.
The CCIL is home to a large collaborative of breast cancer researchers, working together and crossing disciplines to understand the causes of breast cancer, improve diagnostics, create more effective treatments with fewer side effects, and ultimately, save lives. As always, it takes a team of scientists to arrive at such a milestone as licensing a new cancer therapeutic. The labs of CCIL researchers Tim Fan and Erik Nelson have also provided instrumental research support in the development of the novel anticancer compound TEQ103.