The MYC Oncoprotein: A Potential Target for All Human Malignancies
Cancer remains a formidable adversary in the ever-evolving landscape of global health challenges. The World Health Organization (WHO) report underscores this, revealing more than 19.3 million new cases and 10 million deaths in 2021—the projected 47% increase in the cancer-related burden by 2040 highlights an urgent need for more effective therapies. Despite notable advances in oncology, the stark reality is that only about 7% of cancer patients benefit from all FDA-approved targeted therapies. This significant gap primarily arises from the complex physiological roles of most oncogenic drivers and their intrinsic undruggability.
A prime example is the MYC oncogene, which is deregulated in up to 70% of human malignancies and is associated with aggressive, hard-to-treat cancers. MYC accelerates tumor growth and compromises immune checkpoint efficacy, fostering resistance to various targeted therapies. The development of effective MYC-targeted therapies could be a game-changer in cancer treatment. Yet, it is hindered by the critical cellular roles of MYC and the challenges in selectively targeting it with small molecules. This has been a persistent hurdle since the cloning of this formidable oncogene by Dr. J. Michael Bishop’s research group more than four decades ago, with targeted therapies against MYC-driven tumors still in their infancy.
Anticancer Bioscience: A Pioneer in MYC-Synthetic Lethal Therapy
Anticancer Bioscience (ACB), a trailblazer in precision oncology, is addressing this unmet medical need with its focus on synthetic lethal cancer therapies. Founded by Dr. Dun Yang and mentored by Nobel laureate Dr. J. Michael Bishop, ACB integrates innovative strategies across basic research, translational studies, and drug development. This holistic approach is pivotal in crafting advanced cancer therapies stemming from breakthroughs in basic cancer research.
ACB’s innovative approach to exploiting MYC overexpression vulnerabilities opens a new frontier in targeting previously inaccessible areas while preserving MYC’s essential physiological functions. The crux of synthetic lethal therapy lies in leveraging an oncogenic alteration without directly targeting it. This method exploits the vulnerabilities that cancer cells inadvertently expose because of relying on specific oncogenic drivers for survival and proliferation. This unique vulnerability offers a strategic target for interventions that selectively induce apoptosis in cancer cells instead of normal cells. Notable successes include the treatment of BRAC1/2-deficient cancer with PARP inhibitors, showcasing the potential of synthetic lethality.
During his postdoctoral work at the University of California, San Francisco, Dr. Dun Yang laid the foundation for ACB’s focus on MYC-synthetic lethal therapies. Working alongside Dr. J. Michael Bishop, Dr. Yang co-discovered a therapeutic synthetic lethal interaction between overexpression of MYC and disablement of the chromosomal passenger protein complex. This groundbreaking discovery has inspired ACB to develop next-generation MYC-synthetic lethal therapies. ACB’s dedication to synthetic lethal drug discovery is both a scientific choice and a strategic imperative, targeting MYC’s vulnerabilities to fulfill a critical medical need and potentially revolutionizing cancer treatment.
Drug-GPT and MIPS-guided Lead Discovery and Optimization
In its quest to develop groundbreaking therapies, ACB has curated unique compound libraries, including a comprehensive natural products library and a synthetic GUNS-DF compound library. These real libraries, augmented by an AI-driven virtual small-molecule library, are instrumental in identifying novel lead compounds. ACB mainly employs two proprietary approaches for lead discovery and optimization: DrugGPT, an AI platform designed for generating and screening drug-like molecules, and MIPS, mechanism-informed phenotypic screening assays. These innovative tools are central to ACB’s strategy in identifying and fine-tuning potent MYC-synthetic lethal drug candidates, focusing on compounds that trigger MYC-primed lethality, induce proliferative arrest, and modulate the tumor immune microenvironment.
Sole-in-Class MYC-Synthetic Lethal Drug Candidates
ACB has made significant strides in its MYC-synthetic lethal cancer therapy program, developing several classes of unique compounds effective against MYC-overexpressed cancers. A key achievement is the development of JMBI-001, a potent, orally bioavailable small-molecule drug candidate targeting MKLP2-mediated cellular processes. JMBI-001 is a multifaceted inhibitor, inducing autonomous cancer cell death and activating systemic anti-tumor immunity. In preclinical models, JMBI-001 demonstrated remarkable growth inhibition across many tumors, outperforming first-line and immune checkpoint therapies in several mouse tumor models. This efficacy, coupled with a promising safety profile and validated pharmaceutical (PD) markers, positions JMBI-001 as a strong contender for clinical trials.
Expanding the Army of Therapeutics against MYC Tumors
As ACB approaches clinical trials, the challenge of drug resistance, common in molecularly targeted therapies, is a key focus. To combat this, ACB is exploring additional MYC-synthetic lethal compounds with diverse scaffolds to inhibit MKLP2 and pursuing dual-action compounds targeting MKLP2 and either an immune checkpoint protein or the MYC oncoprotein. This proactive approach is underpinned by ACB’s advanced AI-driven drug discovery technology, significantly expediting the design of multi-targeting compounds.
Visionary Leadership and Collaborative Impact
Under Dr. Yang’s visionary leadership, ACB stands as a paragon of innovative, science-driven biotechnology committed to developing first-in-class drugs. Their collaboration with the J. Michael Bishop Institute of Cancer Research ensures a seamless transition of breakthroughs in basic research to practical clinical applications. This synergy is crucial in developing cutting-edge cancer therapies and addressing urgent and unmet medical needs. ACB’s journey, characterized by innovation and a dedication to developing first-in-class drugs, echoes its unwavering vision: to profoundly impact the lives of cancer patients globally. Their recent advances in the MYC-synthetic lethal therapy program herald a new era in targeted cancer therapy.
ACB’s business model seamlessly integrates basic cancer research with translational studies, bridging the gap between academic discoveries and clinical applications. Their collaboration with the J. Michael Bishop Institute of Cancer Research ensures the rapid transformation of breakthroughs into tangible treatments. This partnership is pivotal in developing revolutionary cancer therapies and fulfilling urgent medical needs. ACB’s progress in the MYC-synthetic lethal therapy program marks a milestone in targeted cancer therapy, offering new hope to those battling this devastating disease.
“We are resolute in our mission to advance innovative science and develop first-in-class drugs that make a profound difference to patients worldwide.”