From a Small Village in China to Cutting-Edge Clinical Cancer Research for Cynthia X. Ma, MD, PhD

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Cynthia X. Ma, MD, PhD, was born in a small village in Hebei, a province in the Central China region. “I grew up in a poor village with less than 1,000 people. We had no medical services in our village, so we had to travel to the city to see a doctor, which was quite some distance away. In the 1960s, the transportation system in China was not modernized, so it was challenging to access medical care. Growing up, my younger brother tended to get sick a lot, and I saw how it stressed my mother, given she couldn’t just take him to see a doctor. I think her vulnerability influenced me, and I wanted to be in a career that allowed me to help people get through difficult times,” said Dr. Ma. “As early back as I can remember, I wanted to become a doctor.”

Cynthia X. Ma, MD, PhD

Cynthia X. Ma, MD, PhD

Launched by Mao Zedong, the Chinese Cultural Revolution was a sociopolitical movement from 1966 until his death in 1976, which was characterized by violence and widespread societal disruption. Dr. Ma shared her memories of this time: “I had just finished elementary school as the Cultural Revolution ended. At that point, the Chinese government began putting a tremendous effort in public education, reinstating, for one, the college entrance exam. Moreover, the government initiated an elite school program for high achievers in middle and high school. To be accepted, you had to score high on several difficult entrance exams, which I was fortunate enough to do. I was one of the first groups of students to attend the elite program, which were like private boarding schools in the United States. When I look back, it was run almost like a military camp. We were structured from morning exercises straight through our long day of studies. I must say, that early rigorous training helped prepare me for the rigors of medical school,” Dr. Ma shared.

Upon graduating from high school, students in China undergo the rigorous National College Entrance Examination, considered among the world’s most challenging, which determines one’s college and career path. “Based on the scores, students are then offered college options,” Dr. Ma explained. “The entrance scores to medical school tend to be among the highest, and I was fortunate to be accepted to Beijing Medical University.”

Dr. Ma continued: “The medical school education at Beijing Medical University at that time was a 6-year program, with the first 2 years being a general college curriculum, with an emphasis on science. The last 4 years were strictly medical study and clinical training. I graduated in 1990 with my medical degree, and unlike in the United States, where newly graduated doctors must take the U.S. medical licensing exam, in China, you go straight to work in a hospital. I chose to remain at a hospital affiliated with the medical university, which is where I did my internal medicine residency.”

A Growing Interest in Biology

Throughout medical school during basic science training, Dr. Ma’s interest in biology intensified. After her first year of residency, she came to the United States to pursue further study and training at the University of Cincinnati.

Dr. Ma commented: “My thesis project was to investigate mechanisms of gene regulation during embryonic development under the mentorship of Dr. Jun Ma. I spent 5 years there in training. For my PhD qualification exam, I proposed a project to study the function of the tumor-suppressor gene retinoblastoma (Rb), which accelerated my interest in cancer biology. After attaining my PhD, I stayed on at the University of Cincinnati as a postdoctoral fellow in Dr. James Fagin’s laboratory studying thyroid cancer,” she said.

Despite her interest and growing success in basic cancer research, Dr. Ma missed the clinics and the personal interactions with patients. So, she took the U.S. medical licensing exams and continued her long journey from China into a residency program at New Hanover Regional Medical Center, Wilmington, North Carolina, which is affiliated with the University of North Carolina.

Dr. Ma continued: “I didn’t really think about oncology until my second year, which is usually the time residents begin to decide on a subspecialty. I was intrigued by oncology on the clinical side, because patients with cancer tend to have a lot of complications and comorbidities that need to be addressed. I clearly remember a patient of mine who had a history of breast cancer and was treated with anthracycline. Although her breast cancer treatment was successful, she later developed leukemia, which had a big impact on me. I thought about her and decided I’d like to pursue a career in oncology and develop therapies that would produce better outcomes for patients like her,” she related. “I also felt that my studies in developmental biology and training in endocrinology would help me in that pursuit.”

A Decision During Fellowship

Following her residency, Dr. Ma was accepted for a hematology and medical oncology fellowship at the Mayo Clinic in Rochester, Minnesota. 

During the fellowship program, Dr. Ma met Dr. Alex Adjei, who is well established in phase I drug development and mentored her on designing and conducting clinical trials. “I also spent 2 years in the pharmacogenomic laboratory of Dr. Richard ­Weinshilboum,” she added. “One project was to investigate genetic polymorphisms of CYP19A1 (aromatase gene) in four different ethnic groups and their impact on aromatase enzyme activity, response to aromatase inhibitors, and estrogen regulated phenotypes such as mammogram breast density and bone mineral density.

Dr. Ma noted that her training with Dr. Adjei and the lab research with Dr. Weinshilboum cemented her desire to pursue breast cancer and developmental therapeutics as her research interest. She completed her fellowship in 2005 and joined the faculty of the Washington University School of Medicine in St. Louis.

“As a junior faculty, I was fortunate to have the mentorship of several people, in particular, Dr. Matthew Ellis and Dr. Helen Piwnica-Worms, whose mentorship helped me to establish my career not only as a breast oncologist, but as a clinician-scientist involved in clinical trials and laboratory research,” stated Dr. Ma.

Dr. Ma is leading the Alliance phase III neoadjuvant endocrine study, the ALTERNATE trial, which is focusing on developing biomarkers that guide treatment approaches for postmenopausal women with clinical stage II or III estrogen receptor–positive HER2-negative breast cancer. This trial was built upon the prior neoadjuvant studies conducted by Dr. Ellis. “We’ve enrolled over 1,400 patients in the study, and biospecimens are being analyzed to identify potential genomic predictors of endocrine therapy response and novel therapeutic targets in endocrine-resistant tumors.

“From Dr. Helen Piwnica-Worms, I learned a lot about cell-cycle checkpoints and the design of preclinical studies,” said Dr. Ma. “Recognizing the importance of mentorship, I do my best to guide the career development of our trainees and junior faculties.” 

Her Own Laboratory

Dr. Ma’s laboratory focuses on studies of biomarkers and resistance mechanisms for drugs that target the cell cycle and PI3K pathway through analysis of clinical specimens and preclinical studies using breast cancer cell lines and patient-­derived xenograft models. “We study tumor material from patients enrolled in trials and validate the findings using cell lines in preclinical models. My lab investigates the predictors of drug response as well as looking at ways to develop novel strategies to overcome drug resistance mechanisms.” Dr. Ma is leading the breast cancer project as part of the Washington University PDXNet U54 grant to develop novel treatment approaches using patient-­derived xenograft models.

Dr. Ma described herself as a translational researcher. “Over the years, I have designed and conducted multiple phase I/II trials during which I have collaborated with the National Cancer Institute and industry. My position here at Washington University has given me a unique opportunity to connect the laboratory with the clinic, so I’m very fortunate,” she noted. “I’m the clinical PI on two ongoing level 3 Department of Defense grants, for example, targeting the HER2 mutation with Dr. Ron Bose, and more recently, a study of MK2 pathway inhibition to target tumor-associated stroma with Dr. Sheila Stewart. I believe in team science in accelerating progress and found it particularly rewarding in developing multidisciplinary projects.” Dr. Ma has multiple other collaborative projects within and outside Washington University, with the goal of developing better treatments for breast cancer.”

Kids and Animals

We asked Dr. Ma what she does to decompress after long days of cancer research. “That’s a good question,” she said, “because I am so busy doing work that I love, so I don’t think of it that way. But I do enjoy cooking and sitting down with a good book. I also really enjoy plants, which are abundant in and around our house. However, I guess what gets me away from work most is playing with our two children and our cats and dogs. Kids and animals. Other than that, nothing too exciting, but it’s a lot of fun.” 

DISCLOSURE: Dr. Ma has served as a consultant for Gilead, ­AstraZeneca, Sanofi-Genzyme, Jacobio, Natera, Novartis, Inivata, and  Biovica; and has received research funding from Pfizer and Puma.