Tell us a bit about your work at Anticancer Bioscience
At Anticancer Bioscience (ACB), we are applying our synthetic lethal expertise to the discovery and development of better cancer therapies. We were formed to commercialize innovations emerging from the prestigious J. Michael Bishop Institute of Cancer Research (MBICR), named after the American Nobel laureate J. Michael Bishop, who also chairs the scientific advisory board of the Institute. The MYC oncogene was discovered in J. Michael Bishop’s lab four decades ago. MYC overexpression occurs in 50-70% of cancer patients and is usually aggressive cancers, poorly differentiated and difficult-to-treat.
Although MYC is generally considered an important and broadly applicable oncology target, there is no targeted therapy available for people affected by the most common oncogenic driver of tumour growth. One of our innovative approaches exploits a synthetic lethal interaction between MYC overexpression and a therapeutic effect, allowing the selective killing of cancer cells with overexpression of MYC while sparing normal cells.
This approach opens a new avenue to drug MYC associated cancers as well as overcoming the potential adverse side effects of direct inhibition of MYC. Another revolutionary approach we are taking is restoring contact inhibition of proliferation in cancer cells, rather than killing them. We now have drug candidates for both therapeutic approaches and are working on advancing them into the clinic.
Source: Anticancer Bioscience
What inspired you to focus on cancer?
Cancer is an important global challenge we face today. As a leading cause of death worldwide, cancer accounts for nearly 10 million deaths in 2020. By 2040, the number of new cancer cases per year is projected to reach 29.5 million and the number of cancer-related deaths to 16.4 million. Breakthroughs in oncoprotein-targeted therapies and immune checkpoint therapies have revolutionized cancer treatment in the past two decades.
However, many human cancer patients still have a poor life expectancy due to a lack of effective treatments. We need innovative therapeutics, and I am proud to be part of a worldwide effort to make this happen. My PhD training under Prof. Robert Lloyd at the University of Nottingham in the field of synthetic lethal genetic analysis of pathways involved in DNA recombination, replication, and repair provided the ideal background to exploring these mechanisms in cancer. The success of PARP inhibitors as synthetic lethal therapies against cancer cells defective in DNA repair further prompted me to apply my expertise in synthetic lethal analysis to develop innovative cancer therapies.
What improvements in care and/or treatment would you like to see for cancer patients in the near future?
The most recognizable synthetic lethal cancer therapeutics currently on the market are the PARP inhibitors, which have found use in cancers with DNA-repair deficiencies, such as those associated with BRCA mutations. Given the enormous success of PARP inhibitors and thus the synthetic lethal approach in general, we expect many more synthetic lethal cancer drugs to emerge in the coming years. This includes targeting newly uncovered dependencies that we have thus far not fully appreciated.
Furthermore, as individual cancer cells may harbour unique combinations of genomic and epigenomic events, precision medicine would allow patients to receive treatments tailored to their genome. With the improvements in precision medicine, particularly, advances in biomarker discovery and monitoring technologies, we will be able to determine which drug or drug combinations a patient would most likely respond to, when to use a targeted drug, when to adjust the dose, and when to switch to an alternative therapeutic approach, etc. At ACB, predictive biomarkers for our therapies are under development in parallel with drug development.
Additionally, we are employing machine learning technologies to accelerate our R&D process. We would like to see our innovative therapies together with their biomarkers take precision medicine to the next level and benefit millions of cancer patients worldwide in the future.
Tell us a bit about your journey, how did you come to be in your role?
I come from a genetics background with an emphasis on synthetic lethal screening and analysis. During my PhD training, I worked on genes involved in DNA replication, repair and recombination. Changes in these genes cause genome instability, which is a hallmark of cancer. Applying the knowledge to develop synthetic lethal cancer therapies to benefit cancer patients is always my dream and is a natural extension of my basic research.
Another founder and the CEO of ACB, Dr. Dun Yang, together with Dr. J. Michael Bishop at the University of California, San Francisco, has pioneered a synthetic lethal strategy to treat cancer overexpressing MYC. Drs. Yang and Bishop are also the inventors of the famous esiRNA method of RNA interference in mammalian cells. I contacted Dr Yang to discuss a potential collaboration to design a novel synthetic lethal screen with esiRNA to identify synthetic lethal targets in cells overexpressing MYC. Years later, I was offered the dream opportunity to co-found the Institute (MBICR) and ACB, I had no hesitations at all.
Since the foundation of ACB, I have led the effort to build our proprietary natural products library that is compatible with high-throughput and high-content screening, and develop synthetic lethal screening platforms to identify compounds against cancer cells with MYC overexpression, p53 inactivation, polyploidy, or supernumerary centrosomes. I am also responsible for managing our brand awareness and communications – to ensure international collaborators and investors are aware of our innovative science and commercial potential.
What is the best piece of advice you can offer to others following in your footsteps?
Before I started the journey with ACB and MBICR, I had always been in academia. Without experience in industry and entrepreneurship, it has been a learning curve for me, and I am very much enjoying it. My first advice would be to stay curious, to embrace new things and new ideas as I believe curiosity drives creativity and innovation, which are fundamental in many sectors including drug discovery.
Second, be patient, as it takes time to translate discoveries in basic research into novel therapeutics.
Third is to build a supportive network and learn from the advice of experienced others. Last but not least, be confident, as confidence can help us push the boundaries for growing the business or organisation that we are a part of.
-Jing Zhang
