September is Blood Cancer Awareness Month: 5 Questions with A/Prof Takaomi Sanda

1) How did you embark on your journey as a researcher?

Several factors have affected my career decision to embark on my journey as a researcher in hematology and oncology.

The first factor was my first patient I saw as a medical doctor on the first day of my residency training in 2000. She was suffering from malignant lymphoma; a type of blood cancer. She had a big swelling on her face and her nose was distorted. However, she never gave up hope. After she received irradiation and high-dose chemotherapy followed by an autologous hematopoietic stem cell transplantation (HST), she was cured and her face returned to normal. Her strong willpower has left a deep impression on me. At the same time, I became interested in the characteristics of blood cancer as well as the concept of chemotherapy. I started to ponder on questions like, “Why does blood cancer cells spread so rapidly and aggressively?” and “How can chemotherapy eliminate cancer cells?”  It was then that I decided to work in hematogy and oncology.

The second factor was the emergence of a new drug in 2003 which made me decide to embark on basic research. At that time, I was doing my speciality training in hematology and oncology to learn about HST. One of the main target diseases for HST before 2003 was chronic myeloid leukemia (CML).  This cancer occurs in elderly patients, and HST was the only way to cure this disease back then. Although HST has risks including therapy-related death, many patients selected this option. However, a dramatic change happened in 2003. An oral drug called “imatinib” was approved for CML in many countries. This drug directly targets the oncoprotein (“BCR-ABL”) in CML and specifically kills leukemia cells with minimum toxicities. After the emergence of this drug, the number of cases requiring HST was reduced. Elderly patients who were not suitable for HST were able to receive imatinib therapy. As a result, this drug completely changed the therapeutic strategy for CML. Concurrently, another antibody drug (“rituximab”) that targets a specific protein expressed on malignant lymphoma cells was also approved, which further improved the clinical outcomes for the patients. Many other drugs have also been developed for myeloma, another type of blood cancer. I felt that this was really the beginning of molecularly targeted therapy for patients with blood cancers. I was very lucky because I was able to experience these dramatic changes on the ground and this prompted me to focus my work on hematology-oncology research.

The last factor was the development of next generation sequencing technology which became available around 2008 when I was doing my post-doctoral training. This made many paradigm shifts in biomedical research over the past decade. For example, the first cancer genome was reported for acute myeloid leukemia. My own study also demonstrated the importance of enhancers which are located in non-coding elements. I felt lucky again because I was able to experience another dramatic change on the ground but as a researcher. I was so excited to be part of such a monumental moment. These factors were enough for me to decide to continue my career as a blood cancer researcher.

2) What is blood cancer to you?

I think that blood cancer is the best “model disease of cancer” and the best “model area of biology”. Many findings and therapeutic strategies were derived from the research on blood cancers. The concept and push to develop molecularly targeted therapies for cancers and other diseases came about from the success of imatinib, which is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in health system. In addition, HST is a prime example of stem cell biology and regenerative medicine. Also, many initial genomic studies were conducted for blood cancers. But, why do we begin with blood cancers? There are several advantages in doing research on blood cancers. Firstly, these cancer cells are relatively easy to obtain from peripheral blood and can be cultured in media. Secondly, blood cancers are relatively simple compared to solid cancers in terms of genetic abnormalities, thus enabling us to pinpoint critical mechanisms. In my opinion, the knowledge gathered from blood cancer research can help to establish new concepts and strategies for application on other complex cancers.

3) Why did you choose to focus your work on Blood Cancer?

I believe that hematology and oncology is the field which can contribute to both basic research and public health. Like the case of imatinib, many basic findings often directly lead to the development of therapy. This is a clear example of “From bench to bedside”. Also, working in hematology and oncology gives us a lot of experience both as a clinician and a researcher. For example, to understand blood cancer, we must also understand other organs, because blood cancer cells can spread all over the body. High dose chemotherapy and HST often cause many adverse effects. Hence, clinical hematologists must know how to monitor systemic conditions and how to control clinical complications in other organs (such as pneumonia, cardiac failure, etc). Thus, we can learn many things other than the primary diseases.

I should also highlight that blood is a highly organized, dynamic and specialized tissue, which includes white blood cells, red blood cells and platelets. White blood cells are the main players of immunity, while other cells have different functions. In other words, to understand blood, we must also understand developmental biology (hematopoiesis), immunology, and virology. Studying blood cancers allows the researcher to consider diverse points of view and this is why I decided to specialise in  hematology and oncology.

4) What would you advise to-be researchers pursuing blood cancer research?

As stated above, my career decision was affected by many “extrinsic factors” (my first patient, imatinib, and next generation sequencing), which boosted my “intrinsic factor” (original scientific curiosity). I think that young people have a high degree of plasticity (like “hematopoetic stem cells”). After being exposed to many extrinsic factors, we may be differentiated into specialists (like “white blood cells”). I strongly believe that blood cancer is one of the leading fields of cancer research both in basic and clinical medicine. This may be one of the most competitive research areas, but this can be our motivation as well. I can say that blood cancer is one of most stimulating and rapidly-changing research field and will most definitely make your life more exciting too!

5) What other information would you like to share with the public about #BloodCancerMonth?

My ex-mentor in clinical hematology always told me that One drop of blood gives us a lot of critical information.  Do not waste it!”.  I always keep this in my mind…