Dr Mads Daugaard of Rakovina Therapeutics On The 5 Things Everyone Needs To Know About Cancer

An Interview With Savio P. Clemente

There is no silver bullet for cancer and future management will consist of combinations of treatments with multiple shots on goal for most cancer types. Because individual tumors constantly evolve and adapt to their environment, it is unlikely that a single treatment will sufficient. Rather a combination of treatments will offer effective management.

Cancer is a horrible and terrifying disease. There is so much great information out there, but sometimes it is very difficult to filter out the noise. What causes cancer? Can it be prevented? How do you detect it? What are the odds of survival today? What are the different forms of cancer? What are the best treatments? And what is the best way to support someone impacted by cancer?

In this interview series called, “5 Things Everyone Needs To Know About Cancer” we are talking to experts about cancer such as oncologists, researchers, and medical directors to address these questions. As a part of this interview series, I had the pleasure of interviewing Dr Mads Daugaard.

Dr. Mads Daugaard is a senior research scientist and principal investigator at the Vancouver Prostate Centre specializing in pre-clinical and translational cancer research. He earned his PhD from the Faculty of Health Sciences at the University of Copenhagen in 2007. Dr. Daugaard’s work focuses on sugar-modifications of proteins in solid tumors, DNA repair mechanisms, chemotherapy resistance, and immune-evasion mechanisms in cancer. Additionally, he is a biotech entrepreneur, co-founding companies such as VAR2 Pharmaceuticals, VarCT Diagnostics, Rakovina Therapeutics, and SnapCyte Solutions.

Thank you so much for joining us in this interview series! Before we dive into the main focus of our interview, our readers would love to “get to know you” a bit better. Can you tell us a bit about your childhood backstory?

I grew up in Copenhagen as an only child to my mother Hedvig (who was a school teacher) and my father Poul-Erik (who was a professor at Copenhagen Business School). My mother and father separated when I was 4 years old, so I had two homes during most of my childhood. I got interested in biology early on during high school, but after high school, and before I started University, I traveled south east Asia for a year just me and my backpack. When I got back home, I started the BSc program in biology at University of Copenhagen and, in the beginning, I was excited about the more classical biology topics, such as zoology, and in particular the study of mammals. It was not until 2nd or 3rd year, where I got exposed to molecular biology, biochemistry, and genetics in the context of diseases, that my interest in cancer biology and research started. Since then, it has been full speed ahead.

What or who inspired you to pursue your career? We’d love to hear the story.

I think I have had many defining moments during my education, training, and career, that have all contributed to my path and where I am today. In my earlier career, I want to highlight my MSc and PhD supervisor Dr. Marja Jäättelä (Danish Cancer Society) who was key for cultivating my curiosity in cancer research and for my career choices going forward. She has been a life-long mentor to me and even today, we have joint research projects together. In the later stage of my career, Dr. Poul Sorensen (BC Cancer Research Centre) has been instrumental for my career choices and continues to be a close friend and colleague.

This is not easy work. What is your primary motivation and drive behind the work that you do?

I think I have two complementary drivers related to my research on cancer. The first one is very academic and is related to a desire to understand biological life in its finest detail. For understanding how cells and organisms work, it is helpful to study conditions where it does not work properly, such as when cells become cancer cells, and organisms develops tumors. The second motivation is a sense of duty to use all this knowledge developed in my research to devise strategies that can help people. I think most families have experienced cancer one way or another, and appreciate the potential devastating impact this disease can have on individuals and families as a whole.

What are some of the most interesting or exciting projects you are working on now? How do you think that might help people?

In my capacity as senior research scientist and principal investigator at the Vancouver Prostate Centre, Vancouver Coastal Heath Research, and associate Professor at University of British Columbia, I run a number of basic and early-translational research programs that aims at discovering vulnerabilities in cancer cells that we can target with novel therapies. I call this ‘the sandbox’ because this is where I can think out of the box and where I develop and test new ideas. In the more translational space, I am very excited about our company Rakovina Therapeutics where we are developing next-generation drugs that target tumor cells’ ability to repair damage to their DNA. We have recently integrated cutting-edge AI technology into our workflows that is speeding up the development time significantly. This is very exciting and something that I predict will revolutionize drug-development in general and importantly allow Rakovina to develop, test, and qualify DNA damage response inhibitory cancer drugs for patients in a timely manner. I am also excited about our progress in developing first-in-class glycan-targeting drugs and companion diagnostics in VAR2 Pharmaceuticals and VarCT Diagnostics, which I also think could have profound impact on cancer treatments in the future. Lastly, I would like to mention our most recent UBC spin-off company SnapCyte Solutions where we develop AI software technology for analyzing cells in life science research. We need good research tools to make good drugs, so this activity is kind of foundational for the research in general.

For the benefit of our readers, can you briefly let us know why you are an authority about the topic of Cancer?

Well, I think such a question is best asked to my peers. With my 20 years working in the field, my contributions to the cancer research field have been multifaceted in the sense that in addition to having made key discoveries in various aspects of tumor biology, I have also translated these discoveries into commercial and clinical paths. I have been fortunate to contribute to many different elements of the cancer research during my career. This experience can now be passed on to the next generation of cancer biologists that can build on past knowledge and undoubtedly move even bigger mountains in the future.

Ok, thank you for all of that. Let’s now shift to the main focus of our interview. Let’s start with some basic definitions so that we are all on the same page. What is exactly cancer?

Yes, the short answer is that cancer is a genetic disease, which essentially means a disease caused by alterations in our DNA.

What causes cancer?

The alterations in DNA can in some instances be something we are born with, but in most cases, these changes are acquired during the better part of a lifetime. This is also why cancer incidents in general correlate with age. Some of these acquired alterations happen naturally when cells divide simply because the cellular machinery that copies our DNA makes errors. Alterations in DNA can also be caused by exposure to environmental substances that can amplify the overall burden of DNA alterations that are potentially cancer promoting. As such, there is a tremendous amount of randomness in the cause of cancer.

What is the difference between the different forms of cancer?

In principle, cancer can occur in any cell type that can divide. Until relatively recently, cancers were mainly classified according to how they looked under a microscope and what organ they originated from. With the age of genomics that took off not more than 15–20 years ago, we have been able to look at cancer in a different way. We can now develop molecular maps of different tumors and get detailed information on the genetic alterations that exists in individual tumors. That has revolutionized our understanding of cancer and enabled us to classify subtypes of cancer based on patterns of genetic alterations and how genes are expressed. So nowadays, different forms of cancer are not only defined based on tissue of origin but also defined based on molecular profiles and the functional consequences of specific genetic alterations in the disease. This in turn has enabled personalized cancer therapy where therapeutic decisions are based on molecular profiles rather than the organ from which the cancer originated.

I know that the next few questions are huge topics, but we’d love to hear your thoughts regardless. How can cancer be prevented?

Cancer cannot be completely prevented. It is a numbers game of genetic alterations. And again, that is why cancer risk increases with age. Humans live longer today than 100 years ago and that extends the runway for accumulating cancerous combinations of genetic alterations. We cannot control the genetic luggage that we are born with, or the rate of errors that cells have when they divide. But we can to a certain point control the environment that contributes to the accumulations of genetic alterations during a lifetime. With environment I mean all things that we are exposed to though our lifestyles (e.g., what we eat, drink, smoke, and expose our body to). But this is where it gets complicated. In addition to affecting occurrence of genetic alterations that in themselves may be harmful, the environment also affects our immune system that is a primary defense against damaged cells. In principle, every day we will have cells dividing that are damaged in a way that could potentially cause cancer, but these cells are normally eliminated by our immune system. So, a lifestyle that compromises the function of our immune system could potentially contribute to cancer risk.

How can one detect the main forms of cancer?

Cancer can be detected in many different ways depending on localization of the tumor and molecular profiles. Some cancer types can often be detected by visual inspection such as breast cancer or melanomas. For other cancers like prostate cancer, we have biomarkers that can indicate potential disease. Yet other cancers like colorectal cancer and bladder cancer can often be detected by coloscopy and cystoscopy. There can also be indications in blood samples that would lead to a suspicion of malignant disease. For example, endocrine cancers are often diagnosed based on abnormal concentrations of hormones produced by the affected organ. But common for the majority of cancers, is that the diagnostic work starts when the patient comes into the clinic with symptoms.

Cancer used to almost be a death sentence, but it seems that it has changed today. What are the odds of surviving cancer today?

That completely depends on the type of cancer and the answer is related to the previous question. In general, if the cancer is localized, the odds are very good. However, if the cancer has invaded outside its place of origin and metastasized to other organs than where it originated, the odds of surviving the disease become less favorable. This means that cancer types where you are able to detect the tumor when still localized, generally has a better outcome than tumor types where symptoms develop later in disease progression, and where the tumors consequently are discovered in more advanced stages. But with the advancement of new cancer therapies, there are many tumor types that previously was connected with a death sentence, that are mostly curable today. Good examples of that are testicular cancer and some types of breast cancer. Also, while not curative in the metastatic setting, many of the new generation targeted therapies offer significant extension of survival and better quality of life.

Can you share some of the new cutting-edge treatments for cancer that have recently emerged? What new cancer treatment innovations are you most excited to see come to fruition in the near future?

Numerous new and exciting therapies have emerged during the past decade. There has been a breakthrough in immunotherapies that work by harnessing the patient’s own immune system to combat the cancer. Some tumor types acquire the ability to inhibit the immune system and thereby avoid default elimination. We now have therapies that can interfere with acquired ability and re-activated the immune system to attack the tumor cells. We also have synthetic immunotherapies where we can genetically engineer patient’s immune cells to attach specific proteins that are over-expressed by the cancer cells. This type of therapy has been specifically successful in hematologic cancers and offered complete cures in some instances. We also have new targeted therapies that uses antibodies to detect specific molecular structures on tumor cells and can deliver cytotoxic payloads (antibody-drug conjugates (ADCs)) that in turn will eliminate cancerous cells. In recent years, it has proven an attractive strategy to target specific enzymes in tumors that are required for cancer cells to repair damage to their DNA. This strategy exploits a vulnerability of tumor cells to maintain the capacity to repair DNA lesions that occur during cell division to avoid activation of a suicide program called apoptosis. In my own research, I have a strong focus on ADC development and the development of drugs that target the DNA damage response. For example, in Rakovina Therapeutics we develop next-generation inhibitors of the DNA damage response system in tumor cells that I think can have benefits to many patient groups in the future.

Healing usually takes place between doctor visits. What have you found to be most beneficial to assist a patient to heal?

Beyond having the best possible treatment available, it is important to have a good plan for surveillance after treatment. A good healing process is connected to peace of mind, and a good surveillance program to potentially catch recurrence early on is important. But perhaps equally important, is the feeling of getting back to normal. The faster a patient is able to get back to doing what is loved most without having to deal with issues that decrease quality of life, the better. I think physical healing from a successful treatment is a lesser issue than mental healing and feeling safe with your health and the people you love.

From your experience, what are a few of the best ways to support a loved one, friend, or colleague who is impacted by cancer?

Supporting someone impacted by cancer involves genuine presence and empathy.

• Be Present: Simply being there matters. Listen actively, offer a shoulder to lean on, and let them express their feelings without judgment.
• Open Conversations: Break the silence around cancer. Engage in discussions about their experiences, fears, and hopes. Acknowledge their emotions and validate their struggles.
• Share Moments: Cry together during tough times, but also find moments to laugh and share joy. Humor can be healing, even in adversity.
• Normalize It: Make cancer less of a taboo. Encourage discussions, educate others, and raise awareness. The more we talk about it, the less isolating it becomes.

Remember, supporting someone through cancer is about being there, understanding their journey, and showing unconditional care.

What are a few of the biggest misconceptions and myths out there about fighting cancer that you would like to dispel?

I would like to dispel that a cancer diagnosis is the same as a death sentence. The fact of the matter is that many cancer-diagnoses today are manageable from a clinical perspective. We constantly improve treatment strategies and develop new interventions that will only further improve outcomes and quality of life in the future.

Thank you so much for all of that. Here is the main question of our interview. Based on your experiences and knowledge, what are your “5 Things Everyone Needs To Know About Cancer? Please share a story or example for each.

1) Cancer is a complex and heterogenous disease that behave similar to any type of biological evolution. The genetic alterations accumulated over time are preserved and selected for in the fraction of tumor cells that by chance can escape our immune system or therapeutic interventions. This is the underlying mechanism of tumor evolution and development of therapeutic resistance.

2) Many cancer types are clinically manageable today and not a death sentence. For many cancer types, we now have multiple shots on goal that enable sufficient management. Therefore, cancer is for many patients something you live with and not necessarily something you die from.

3) The pace of development of new treatments for cancer is greater than ever before. The number of clinical trials for both combinations of existing drugs and new first-in-class therapeutics are increasing year over year.

4) There is no silver bullet for cancer and future management will consist of combinations of treatments with multiple shots on goal for most cancer types. Because individual tumors constantly evolve and adapt to their environment, it is unlikely that a single treatment will sufficient. Rather a combination of treatments will offer effective management.

5) Metastatic disease remains a capital challenge. It will require novel innovative treatments to improve outcomes in these patients in the future.

You are a person of great influence. If you could start a movement that would bring the most amount of good to the most amount of people, what would that be? You never know what your idea can trigger. :-)

That is an interesting question. I think I would put an effort into advocating for more compassionate use of new experimental investigative drugs and try to reduce non-medical and economic barriers that sometimes hinder use of medicines across health care systems internationally.

How can our readers further follow your work online?

LinkedIn profile (https://www.linkedin.com/in/madsdaugaard/)

My academic profile can be found here: https://www.prostatecentre.com/about-us/people/dr-mads-daugaard

My work in Rakovina Therapeutics on the development of next-generation DNA damage response inhibitors can be followed here: https://www.rakovinatherapeutics.com and https://www.linkedin.com/company/rakovina-therapeutics-inc/about/ and https://x.com/rakovina_rkv

My work on ADCs and glycan targeting therapies can be followed here: https://var2pharma.com

Thank you so much for these insights! This was very inspirational and we wish you continued success in your great work.

About The Interviewer: Savio P. Clemente, TEDx speaker and Stage 3 cancer survivor, infuses transformative insights into every article. His journey battling cancer fuels a mission to empower survivors and industry leaders towards living a truly healthy, wealthy, and wise lifestyle. As a Board-Certified Wellness Coach (NBC-HWC, ACC), Savio guides readers to embrace self-discovery and rewrite narratives by loving their inner stranger, as outlined in his acclaimed TEDx talk: “7 Minutes to Wellness: How to Love Your Inner Stranger.” From his best-selling book to his impactful work as a media journalist covering resilience and wellness trends with notable celebrities and TV personalities, Savio’s words touch countless lives. His philosophy, “to know thyself is to heal thyself,” resonates in every piece.