Targeting Mutant KRAS Gene Signaling to Slow Tumor Growth

Brian Frenzel is a San Francisco Bay Area based entrepreneur who works in the drug discovery and development field and serves as the CEO of Tosk, Inc. Tosk is dedicated to improving outcomes for cancer patients by developing drugs that block the adverse side effects of existing, widely used, cancer treatments and drugs that block the activity of genes that drive many cancers. Brian Frenzel believes that these efforts have the potential to address the unmet medical needs of more than half of all cancer sufferers.

One example of such a program at Tosk centers on a class of genes know as KRAS which regulate cell growth by functioning as “on/off switches” for the production of proteins that signal cells to grow and divide (proliferate) or to mature and take on specialized functions (differentiate). When KRAS genes mutate, they can get stuck in the “on” position, resulting in uncontrolled cell growth leading to cancer. KRAS genes drive as many as 30 percent of all cancers, including a third of lung cancers, nearly half of colon cancers, and nearly all pancreatic cancers. Despite numerous efforts of pharmaceutical companies and government and academic research laboratories, targeting KRAS genes with drugs to stop or slow their activity has proven very difficult, and KRAS has developed a reputation as being “undruggable.”

Tosk’s innovative approach centers on the KRAS variants that are responsible for most KRAS-driven cancers, known as G12D and G12V. These genes are is also associated with a decrease in the efficacy of EGFR-inhibiting cancer drugs such as Erbitux® in 40 percent of those who are otherwise candidates to receive such therapy. As an indicator of the importance of this work, the US National Cancer Institute has provided Tosk with over $2 million in grant funding support.

Why Fruit Flies Are Used to Understand Diseases and Discover Drugs

Based in Northern California, Brian Frenzel is a longtime new product discovery and development executive in the life sciences industry. Brian Frenzel currently serves as CEO of Tosk, Inc. a company that utilizes fruit flies (Drosophila melanogaster) to discover new cancer drugs.

While fruit flies have an outward appearance that scarcely resembles humans, roughly 60 percent of fly genes can also be found in humans in a similar form with similar function. If you consider genes that cause disease, 75% of the genes that cause disease in humans can be found in Drosophila, and that percentage increases to 90% if you look at genes that can trigger cancer.

At the same time, it is much easier to analyze the fruit fly genome than that of a human, since there are only eight chromosomes in the fly compared to 46 chromosomes in humans and 40 in mice. Consequently, the fly genome was the first to be fully mapped, accomplished in 2000.

Equally importantly for pharmaceutical research, flies are a very inexpensive whole animal discovery tool. Many hundreds of drug candidates can be tested in Drosophila at the same cost as a single test in a rodent.

Head and Neck Cancer Symptoms and Treatments

California resident, Brian Frenzel graduated from the Stanford University Graduate School of Business, where he obtained a master of business administration specializing in corporate finance. He is also a former officer in the US Navy, where he served as a department director and taught undergraduate and graduate level courses in mathematics and physics at the US Navy Nuclear Power School. Brian Frenzel currently serves as the chief executive officer of Tosk, Inc., a company that develops treatments for head and neck and other cancers.

Head and neck cancer is a life-threatening condition that accounts for approximately four percent of all cancers in the US. Cancers that are known collectively as head and neck cancers usually begin in the squamous cells that line the mucosal surfaces of the head and neck, for example, those inside the mouth, throat, and larynx. Head and neck cancer can also occur in the sinuses, the tongue, the nose, and the salivary glands. There has been slow, but steady, progress in the treatment of head and neck cancer over the years, resulting in a five-year survival rate of about 50% in the US.

The most common treatments for head and neck cancer are surgery, using lasers or excision, radiation therapy, using high energy x-rays or beams of protons to kill cancer cells in the tumors, and chemotherapy, using drugs such as cisplatin and methotrexate. These methods can be used alone or in combination. Recent advances in immunotherapies, which activate the patient’s immune system to fight the cancer, are also used in later stage head and neck cancer. The most common of these are the recently approved drugs, pembrolizumab (Keytruda) and nivolumab (Opdivo).