How Cancer Uses an “Invisibility Cloak” - And How Kazia Therapeutics Is Trying to Remove It

We all know that cancer is caused by the rapid growth of tumor cells - but the ability for cancer to hide from the immune system is also a big challenge that scientists face when designing new therapies. In this episode of Rx for Biotech, host Chris Leidli speaks with John Friend, MD, CEO of Kazia Therapeutics, about a new approach to some of the most difficult-to-treat cancers, including glioblastoma, pediatric brain tumors, brain metastases, and triple-negative breast cancer. Dr. Friend uses a powerful metaphor throughout the conversation: many tumors develop something like an “invisibility cloak.” They adapt, resist treatment, avoid immune detection, and become harder for standard therapies to eliminate. Kazia Therapeutics is working to change that. The conversation centers on paxalisib, Kazia’s investigational brain-penetrant therapy designed to inhibit both PI3K and mTOR, two important cancer growth and survival pathways. John explains the PI3K pathway using a simple analogy: in cancer, this pathway can act like an accelerator stuck in the “on” position. By targeting PI3K and mTOR together, paxalisib is designed not only to take the foot off the accelerator, but also to apply the brakes. A major focus of the episode is glioblastoma, one of the most aggressive and difficult-to-treat brain cancers. John explains why glioblastoma has been so challenging for drug development, including tumor complexity, resistance, and the difficulty of getting drugs across the blood-brain barrier. Paxalisib was specifically designed to cross the blood-brain barrier—an essential feature for any therapy being developed for brain tumors. John also discusses Kazia’s expanding work in triple-negative breast cancer, where the company is studying paxalisib as an add-on to standard-of-care treatment with pembrolizumab plus chemotherapy. The goal is not simply to kill tumor cells directly, but to potentially reprogram resistant cancer cells, reduce circulating tumor cells, and make tumors more vulnerable to existing therapies and immune attack. Chapters 00:00 Intro: Paxalisib and the Blood-Brain Barrier 01:02 Meet John Friend, MD, CEO of Kazia Therapeutics 01:18 Kazia’s Australia and U.S. Footprint 03:31 From Practicing Physician to Oncology Drug Development 06:04 Why John Joined Kazia Therapeutics 08:50 Paxalisib and the PI3K/mTOR Pathway 09:40 The Accelerator and Brake Analogy for Cancer Growth 11:01 Why Glioblastoma Is So Difficult to Treat 12:58 The Blood-Brain Barrier Challenge 14:04 How Paxalisib Was Designed to Reach Brain Tumors 15:00 Safety, Tolerability, and On-Target Effects 17:55 Rethinking “More Is Better” in Cancer Drug Development 18:24 Combination Therapy and Cancer’s “Invisibility Cloak” 19:14 Paxalisib Clinical Data in Glioblastoma 21:26 Pediatric Brain Cancer and DIPG 23:28 Triple-Negative Breast Cancer and Unmet Need 25:08 Reprogramming Resistant Cancer Cells 27:16 Adding Paxalisib to Standard of Care in TNBC 28:10 Circulating Tumor Cells and Bench-to-Bedside Translation 29:08 Removing Cancer’s “Invisibility Cloak” 30:15 Kazia’s Pipeline Beyond Paxalisib 31:13 PD-L1, Checkpoint Inhibitors, and Immune Evasion 33:03 Cancer-Specific PD-L1 Protein Degradation 34:00 Key Milestones Ahead for Kazia Therapeutics 35:16 Future Opportunities in Breast Cancer and Colorectal Cancer 36:06 Commercialization, Platform Updates, and Long-Term Vision 37:05 Closing Thoughts 37:54 Rx for Biotech Listener Resources This conversation is especially relevant for patients, caregivers, clinicians, researchers, biotech investors, and anyone interested in the future of brain cancer treatment, glioblastoma research, triple-negative breast cancer, targeted oncology, immunotherapy resistance, and precision medicine. Subscribe to Rx for Biotech for conversations with biotech CEOs, physicians, scientists, and industry leaders developing the next generation of personalized medicines and advanced cancer therapies. This episode is for educational purposes only and should not be interpreted as medical advice. Investigational therapies discussed in this conversation have not necessarily been established as safe or effective by regulatory authorities.