Remembering Jimmie Holland, a Founder of Psycho-Oncology

Source: Memorial Sloan Kettering - On Cancer
Date: 01/09/2018
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On Christmas Eve, Memorial Sloan Kettering and the wider cancer community lost a beloved and brilliant doctor, Jimmie Holland, who died of cardiovascular disease at 89. Dr. Holland was a tireless advocate for supporting the emotional and psychological needs of people with cancer. She also made huge strides in reducing the stigma surrounding the disease.

Dr. Holland was considered a founder of the field of psycho-oncology, which combines oncology and psychiatry. It is increasingly considered a vital part of comprehensive cancer care, largely thanks to her work.

In 1977, Dr. Holland joined MSK as the inaugural Chief of the Psychiatry Service, the first such service at a cancer center anywhere in the world. She was then named Chair of MSK’s Department of Psychiatry and Behavioral Sciences when it was created in 1996. The department was also the first of its kind, and Dr. Holland remained in her role there until 2003. At the time of her death, she held the Wayne E. Chapman Chair in Psychiatric Oncology.

“Jimmie’s death is a profound loss to us all,” says MSK Physician-in-Chief José Baselga. “Through her visionary work she has forever changed the landscape of cancer care.”

Changing World, Changing Needs

Dr. Holland grew up in a tiny town in north Texas, the only child of a cotton farmer and his wife, neither of whom had finished high school. When she earned her medical degree from Baylor College of Medicine in the early 1950s, “cancer”was a word that most people wouldn’t say out loud. Many newspapers and magazines wouldn’t print it, and patients often were not even told of their diagnosis.

That began to change in the 1970s. Better treatments became available and people with once-fatal cancers starting living longer and even being cured. As the wife of James Holland — a leading oncologist and one of the pioneers of chemotherapy combinations — Dr. Holland had a front-row seat from which to witness the medical revolution that was taking place. While her husband and his colleagues focused on curing people of their cancer, Dr. Holland asked a question that none of them were able to answer: How do the patients feel about it?

As a psychiatrist, she had long been interested in studying how people with otherwise good mental health responded emotionally and psychologically to life-threatening illnesses. She called this focus “psychological care of the medically ill.” She began encouraging oncologists who were conducting clinical trials to include questions about patients’ quality of life in their data collection and research.

The Science of Caring

But measuring things like anxiety, depression, and fatigue was not always straightforward. Dr. Holland met this challenge by developing ways to gauge what patients were feeling that went beyond what doctors and nurses could just observe. She worked to create objective scales to evaluate aspects of people’s experience that were once considered immeasurable. This in turn could validate whether psychological treatments were working. Her research brought the emerging field of psycho-oncology into the realm of evidence-based science, which allowed it to become a recognized subspecialty.

During her years at MSK, Dr. Holland created the nation’s largest training and research program in psycho-oncology. In 1984, she produced for MSK the first-ever syllabus on psycho-oncology. In 1989, she was senior editor of the first textbook on the subject. She also shared her knowledge with the world. She co-founded the International Psycho-Oncology Society in 1984 and founded the American Psychosocial Oncology Society in 1986. She is credited with putting psychosocial and behavioral research on the agenda of the American Cancer Society in the early 1980s. She was also a founder and co-editor-in-chief of the journal Psycho-Oncology.

Dr. Holland recognized that people’s psychological distress could linger even after they were considered cured of their cancer. To address this, she advocated for the formation of a program at MSK that today is called Resources for Life After Cancer. It became a model for other similar initiatives around the world.

“Jimmie was a cancer pioneer, a remarkable woman, and a once-in-a-generation influencer,” says William Breitbart, the current Chair of Psychiatry and Behavioral Sciences and the Jimmie C. Holland Chair. “Her death is a profound loss for all of oncology.”

The Sixth Vital Sign

Dr. Holland pushed to recognize patient distress as the sixth vital sign in medicine. (The others are temperature, pulse, blood pressure, respiration, and pain.) She played a key role in the development of the National Comprehensive Cancer Network’s distress thermometer. This enables people to report their levels of anxiety and depression on a scale of zero to ten, similar to the way they rate their pain.

Other topics that were important to her included survivor guilt, diminishing the stigma of a cancer diagnosis, and evaluating ways to lessen cancer side effects like depression, anxiety, and fatigue with medication and other treatments.

In her later years, she also became particularly interested in supporting the psychosocial needs of elderly patients. As part of that effort, she founded the Vintage Readers Book Club, an offshoot of a support group she led on aging and cancer. The participants talked about classic works by writers including Cicero and Benjamin Franklin, and used their discussions as a springboard for talking about wider-ranging topics that were important to them.

“Jimmie was an inspiration on multiple levels, not least of which was her appreciation of the fact that we are more than our careers,” says psychologist and author Mindy Greenstein, who first came to know Dr. Holland when she conducted her fellowship in MSK’s Department of Psychiatry and Behavioral Sciences. The two later worked together and coauthored the book Lighter as We Go: Virtues, Character Strengths, and Aging. “While raising her own family as well as comforting patients and their family members with her Texas warmth and sound insights, she still found the time to accomplish so much in her work. Hers was a life of unique and dedicated service.”

Dr. Holland, who died at home surrounded by family, was still seeing patients up until two days before she died. She is survived by her husband; six children; nine grandchildren; and countless friends, colleagues, and collaborators.

“Jimmie was a true pioneer in the field of psycho-oncology, and her passion for her patients and her research was evident,” says MSK President and CEO Craig Thompson. “She will be dearly missed by the MSK community and by the world.”

8 Questions with Valerie Rusch: Lung Cancer Surgeon Reflects on Advances and Providing Excellent Care

Valerie Rusch is Vice Chair for Clinical Research in the Department of Surgery at MSK. She is a thoracic surgeon who treats lung cancer and esophageal cancer, malignant pleural mesothelioma, and other tumors of the chest. She was the first woman named as a service chief and promoted to full Member in her department at MSK.

1. In October, you will become president of the American College of Surgeons. What does that entail?

The group is the world’s largest surgical organization. It represents 80,000 surgeons across all specialties, both nationally and internationally. Its mission is to improve care by setting high standards for surgical practice and education. I will be the college’s 100th president but only the fourth woman to hold the position. My role is to represent the organization at educational conferences around the world.

2. Did you always know you wanted to be a doctor?

My father was in the Navy Medical Corps during World War II and later became an otolaryngologist. This gave me some exposure to the medical world. In college, I worked as an operating room technician for two summers. My father’s family was Swiss, and a bilingual education was important, so I attended the Lycée Français in New York City. I considered multiple career paths, including being an interpreter, but ultimately was most attracted to medicine. I ended up going to medical school at the College of Physicians and Surgeons at Columbia University.

3. How do you cope with being a woman in a male-dominated field?

There have been challenges. But my father always said, “No one can argue with excellence.” Although I’ve certainly encountered instances of prejudice, I’ve focused on delivering excellent clinical care, helping my patients, and taking advantage of research opportunities to develop new treatments. It has been rewarding to see substantially more women in surgery and to see them increasingly accepted within the surgical community.

4. How did you get interested in thoracic surgery?

During my residency in general surgery at the University of Washington, I was exposed to many surgical subspecialties. I found that thoracic surgery provided a blend of technically challenging procedures and cognitive decision-making. I particularly appreciated the meaningful long-term relationships that develop during the care of people with cancer.

5. When did you come to MSK?

In 1989, I was recruited to travel to New York City and interview for a position at MSK. It came at the perfect time because I had recently decided to focus my career on cancer care. Thoracic surgeons do a lot of different things, including lung transplants, reconstruction after trauma, and treatment of benign diseases. Cancer was where I felt I could make the biggest difference.

6. How has treatment for lung cancer changed over time?

Minimally invasive surgical techniques have made recovery easier, and we can operate more safely on older patients due to advances in pre- and postoperative care. New radiotherapy techniques can help patients who cannot have surgery. Lung cancer screening with CT imaging has led to many more people being diagnosed with very early-stage tumors, when they may be cured by surgery or radiation therapy alone. And targeted therapies and immunotherapies have led to higher survival rates in people with more advanced lung cancers.

7. What is a challenge that remains?

One emotional challenge is the guilt that patients feel because the majority of these cancers are linked to smoking. They tend to hold themselves responsible for their disease. Also, smoking rates have declined in North America but remain high in many parts of the world.

8. How does MSK support people with lung cancer?

We have many medical and psychosocial resources for patients throughout their treatment and afterward. Now that many of our patients are living longer, survivorship care has become important. Subsequent primary lung cancer after successful treatment of an initial lung cancer is a significant risk. We developed the first lung cancer survivorship program nationally to provide lifelong follow-up, supportive care, and screening. It has become a significant part of our care.

Meet Julia Glade Bender, Who’s Focused on Developing Better Treatments for Kids with Cancer

Source: Memorial Sloan Kettering - On Cancer
Date: 09/20/2019
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Julia Glade Bender is a pediatric oncologist and Vice Chair for Pediatric Clinical Research at MSK Kids. She specializes in treating children with solid tumors of the bone and soft tissue, including osteosarcomaEwing sarcomarhabdomyosarcoma, and germ cell tumors.

She is a leader in developing clinical trials and other treatments for children with cancer that does not respond to standard treatment.

We spoke with Dr. Glade Bender about the challenges of treating rare childhood cancers and how personalized medicine is leading to better therapies for tumors that are especially hard to treat.

What makes cancer in children different from cancer in adults?

Most cancer in adults is spurred by a lifetime of exposure to outside factors — like tobacco smoke and UV light — combined with the natural DNA damage that comes with aging. Harmful genetic mutations begin to accumulate and eventually can tip the balance and cause cancer. Childhood cancers, in contrast, are often triggered by a unique event, such as a rearrangement in the chromosomes that creates an entirely new gene. These alterations can happen early in a child’s life or even before they are born.

Additionally, solid tumors in children usually arise in a different type of cell. Most adult cancers are carcinomas, which develop out of the tissues that line the inner and outer surfaces of the body, like the skin and the lining of the intestines and other organs. Childhood cancers are usually sarcomas, which form in cells in the muscles, bones, and other connective tissues.

What are some of the biggest challenges of treating cancer in children?

We can cure 80% of kids with existing treatments, especially chemotherapy, radiation, and surgery. But for the remaining 20%, new options are urgently needed.

Because these cancers are so rare, even if we have an idea of which drugs we should use to treat them, it’s difficult to develop clinical trials. A certain number of patients are required for clinical trials. For rare subtypes of uncommon cancers, which may occur in only a few dozen children in the whole country, this isn’t always possible.

Although we already have successful treatments and can cure the majority of children with cancer, we know that these treatments can have long-term effects on their health, well into adulthood. We hope to eventually develop treatments that don’t have these side effects.

How is targeted therapy changing treatment?

At MSK Kids, all children receive testing with MSK-IMPACTTM. This test helps us find particular mutations that may be driving the growth of tumors and suggest ways to treat them.

Clinical trials developed by MSK’s Early Drug Development Service can now include children as young as 12. Previously the age was 18. Although we always make the case that kids are not just little adults, we know that when it comes to things like side effects, kids over the age of 12 are more closely aligned with adults than they are with younger kids.

For a few mutations, we have drugs that have already been approved for use in kids by the US Food and Drug Administration. The biggest success is probably larotrectinib (Vitrakvi®), which is approved for solid tumors that have a mutation in a gene called NTRK.

For other, rarer mutations, we may develop a protocol for single-patient use (SPU). These compassionate-use plans require tremendous resources, including finding a drug — and a company willing to supply it — then getting permission from the Institutional Review Board and the FDA to administer the drug. It can be a lengthy and labor-intensive process.

We always collect a lot of data when we do SPUs, so that we can learn as much as possible about how and why these drugs work or don’t.

How does research done at MSK Kids help children who aren’t able to come here for treatment?

Because we collect so much information with our SPU protocols, they can eventually lead to clinical trials that may be expanded to other hospitals. That has already happened with five drugs that started as SPUs.

Members of MSK Kids also participate in a number of collaborative groups. I’m involved with the Pediatric MATCH Trial, which is a national effort to get drugs to as many patients as possible. It’s co-sponsored by the National Cancer Institute and the Children’s Oncology Group. We are already looking at eight different parts for different drug targets, and we’re adding new ones all the time.

Through these efforts we not only develop trials but also help set the standard of care for the treatment of children with cancer throughout the country and the rest of the world.

You came to MSK Kids about a year ago, after spending most of your career at another hospital. Can you talk about the move?

One thing that’s really special at MSK Kids is the collaboration with specialists beyond pediatrics, whether that’s scientists working in labs or medical oncologists who work with adults. We have a lot we can learn from one another.

Another thing that’s interesting about being at MSK is that this is where some of the earliest successful treatments for childhood cancer were developed 30 or 40 years ago. And some of those pioneering doctors are still here.

Now we’re at the forefront of this new era in personalized medicine. You’ve got this interplay between the mothers and fathers of chemotherapy and the new leaders in targeted therapy. To cure the greatest number of children, you really need both. 

Meet Maria Jasin, an Award-Winning Biologist Who Studies DNA Repair

Source: Memorial Sloan Kettering - On Cancer
Date: 09/25/2019
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On September 25, Sloan Kettering Institute researcher Maria Jasin was presented with the Shaw Prize in Life Science and Medicine at a ceremony in Hong Kong. The annual Shaw Prizes honor life scientists, astronomers, and mathematicians from around the world who have made significant contributions in their fields of study. The prizes were first presented in 2002, and each comes with an award of $1.2 million.

Dr. Jasin, a member of SKI’s Developmental Biology Program, has received a number of other honors, including the 2018 Basser Global Prize from the Basser Center for BRCA at the University of Pennsylvania. She is also a member of the National Academies of Sciences and Medicine and the American Academy of Arts and Sciences.

We spoke with Dr. Jasin about her research and her collaborations at MSK.

What is the main focus of your work?

I study a process called homologous recombination. This is one of the main ways that cells repair DNA after it is damaged. A particularly dangerous type of DNA damage is a double-strand break, in which the two strands of the DNA double helix break in the same place. These breaks make it difficult for a cell to repair its genetic material.

In homologous recombination, a cell finds a DNA sequence in the genome that resembles the sequence at the break site. It mends the break by copying that undamaged sequence into the broken DNA.

How does your research relate to cancer?

In the late 1990s, I began a project with [Memorial Sloan Kettering medical oncologist and breast cancer specialist] Mary Ellen Moynahan, who was then a member of my lab. She was studying the connections between the genes BRCA1 and BRCA2, which are associated with the suppression of breast cancerovarian cancer, and other cancers. Their absence can also affect therapy response.

We found that when these genes are mutated, cells are prevented from being able to repair double-strand breaks by homologous recombination. When DNA can’t be repaired, damage in the genome can accumulate and eventually lead to cancer.

This research was a basis for other labs developing PARP inhibitors. These drugs are now often used to treat cancers containing BRCA mutations.

Can you explain the contributions your research has made to technologies like CRISPR?

When I started my own lab in the early 1990s, I wanted to study double-strand break repair as it applied to genetic engineering.

We took an enzyme that was used to induce double-strand breaks in yeast and modified it for mammalian cells. We then developed tools that would provide an indication that homologous recombination was taking place and repairing these breaks.

I still remember when my postdoc called me over and showed me the cell culture plate. There were all these colonies growing on it — revealing that we were able to induce a very precise genome modification. It worked! And better than I could have imagined! It was a stunning result. Up until that time, people had assumed that homologous recombination would not work in mammalian cells because, without a break, it was very inefficient. We also observed nonhomologous repair, which led to mutations at the site of the break.

It was clear to me from the beginning that this would be a powerful way to do gene modification. We still had a lot of things to figure out, including how to get DNA breaks at particular sites in the genome. But eventually it formed the basis of a number of gene-editing techniques, including the CRISPR system.

How did you find out that you won the Shaw Prize?

I was in Paris in May attending a conference. When I first got the announcement from the Shaw Foundation, I was so focused on the conference that I didn’t immediately understand they were telling me I had won. Once I figured it out, I was thrilled! I was with Erika Brunet, a former postdoctoral fellow who had organized the conference I was attending, and another former postdoctoral fellow, Fabio Vanoli, who is currently working in MSK’s Department of Pathology. We were able to celebrate a little bit in Paris. That was really nice.

A significant body of your research has focused on meiosis. What is that and why is it important?

Meiosis is the way that germ cells — eggs and sperm — form.

We usually think of double-strand breaks as something that puts the genome at risk for mutations. But meiosis is one case where we need homologous recombination to happen between maternal and paternal chromosomes. During the formation of germ cells, there are usually about 200 double-strand breaks. These breaks ensure that the germ cells get only one set of chromosomes and that offspring have genetic variation. You don’t get healthy sperm and eggs without it.

A lot of my research in this area has been done in collaboration with Scott Keeney [a member of SKI’s Molecular Biology Program]. We’ve worked together for more than 20 years. It’s been a highly productive partnership in terms of successful postdoctoral fellows and publications.

You started working at MSK right after finishing your training, and you’ve been here for your entire independent career. What’s special about working here?

MSK is a great place to collaborate, both with clinical researchers and with other basic science investigators. In addition, we get a lot of support from leadership to be creative when we want to explore a new project or a new avenue of study. A lot of other institutions don’t offer that.

Understanding Biology’s Blueprint: 8 Questions with Kat Hadjantonakis

Source: Memorial Sloan Kettering - On Cancer
Date: 12/30/2019
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Earlier this year, Anna-Katerina “Kat” Hadjantonakis was named Chair of the Sloan Kettering Institute’s Developmental Biology Program. She succeeded Kathryn Anderson, who had led the program since it launched in 2003.

We spoke with Dr. Hadjantonakis about the field of developmental biology and how she got interested in this area of research.

What is developmental biology, and what does it have to do with cancer?

Developmental biologists study the genes, proteins, and other biological phenomena that control how cells multiply, change their identity, and reorganize themselves to give rise to different tissues and organs. This provides a blueprint to understand how our bodies form.

Cancer happens when normal developmental processes go awry. To learn how to fix them, you first need to know how they’re supposed to work.

What is the focus of your research?

My lab uses primarily mammalian models to learn how cells know what to become and how groups of these cells generate the blueprints of organs. We study tissue called the endoderm, which becomes organs, including the lungs, liver, and pancreas. We study how endodermal cells give rise to distinct organs with different functions.

Did you always know you wanted to be a scientist?

I went to school in the UK, and the education system requires that you narrow down your interests early. I excelled at biology and math, so I decided to go in that direction. I also excelled at fine art, especially photography, but sadly was unable to pursue that interest in parallel. I’m dyslexic and have always been better with processing images than words. I did my undergraduate and PhD degrees at Imperial College London. I’ve now come full circle because my lab uses a lot of microscopy, an adaptation of photography.

What led you to MSK?

When I was a postdoc at Columbia University, I met Kathryn at a meeting on mouse genetics. She told me MSK was creating the Developmental Biology Program and that I should consider applying. I was the first person hired after the program started.

Now that you’re Chair of the program, what are your plans for it?

Our first goal is to recruit three or four junior faculty members who will be leaders in their fields. We want people who work on the cutting edge of research, address important unsolved problems, and are collaborative and good institutional citizens. Kathryn is a true role model, and it’s fabulous that she’s staying on as faculty. I have some big shoes to fill.

Where in the UK did you grow up?

I grew up in London, but both of my parents were Greek. Even though I sound British, I have a long, unpronounceable Greek name. Growing up, I used to visit Greece every summer. I speak Greek, but with a British accent.

Do you still make art?

I don’t have time to practice art, but I live in the Chelsea neighborhood, the nexus of many art galleries. So I try to take advantage of those cultural opportunities.

What are your other hobbies?

Listening to music. I used to have a subscription to the Metropolitan Opera, but I relinquished it. Their performances started too early. My schedule is unpredictable, and I often failed to make it across town in time after work.

I cycle as much as I can. I see it as an efficient mode of transport and a decent form of exercise — a surrogate for not getting to the gym as often as perhaps I should! I ride a Citi Bike to work, weather permitting. When I first came to New York, I was petrified to ride here. I used to cycle in London and in Toronto, where I trained. The city has done a lot with building bike lanes and raising awareness of cyclists. I’m now brave enough to venture onto the streets. 

Report cards on women in STEM fields finds much room for improvement

Source: Cell Press
Date: 09/05/2019
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Although women have made important contributions to science throughout history, they have consistently been underrepresented at all levels. Now, data from a four-year study of institutional “report cards” undertaken as part of the New York Stem Cell Foundation’s (NYSCF) Initiative on Women in Science and Engineering (IWISE) suggest that although a growing number of women are training in the sciences, efforts to promote and maintain women in more senior scientific roles are still largely inadequate. Additionally, the researchers report that not enough policies have been put in place to support women in science throughout their careers. The study is being reported September 5 in the journal Cell Stem Cell.

“The data suggest that we are making headway,” says Reshma Jagsi (@reshmajagsi), a radiation oncologist and director of the Center for Bioethics and Social Sciences in Medicine at the University of Michigan and one of the corresponding authors. “That said, there are still many institutions that have few women in senior-most faculty positions. There also remains quite a bit of room for improvement in certain areas, including the representation of women in certain roles, such as speaking at scientific meetings.”

The researchers obtained their data through the use of institutional report cards that were collected when individual researchers applied for grants from NYSCF. The report cards were part of a 2014 NYSCF project that put forward a number of strategies aimed at helping to achieve gender parity in science, technology, engineering, and math (STEM). Of the 1,287 report cards that were submitted, 741 provided complete information for a given year, and some included multiple years. Overall, the data in the paper represent 541 institutions in 38 countries in North America (72%) and Europe (18%).

The investigators found that although women made up more than half of the population among undergraduate, graduate, and post-graduate students, the picture became different as seniority increased. Women made up 42% of assistant professors, 34% of associate professors, and 23% of full professors. These rates varied greatly by institution: At about one-third of the institutions surveyed, women made up less than 10% of tenured faculty recruits.

“We expected to find that women would be better represented at more junior ranks compared with senior ranks,” Jagsi says. “But I found it noteworthy that there were regional differences. For example, institutions in Europe come closer to achieving gender parity.”

The researchers say their findings suggest that the primary issue is not recruiting women into STEM roles but retaining them and promoting them into more influential positions.

They also point out the important part that funding organizations can play. “Funding organizations are in a unique position to require institutional leaders to pay attention to equity, diversity, and inclusion within their organizations,” Jagsi says. “By requiring these report cards, they can promote actions that help all scientists thrive. We hope that other funding bodies, like the NIH, will adopt a similar report card.”

The next phase of IWISE will focus on highlighting best practices undertaken by institutions. This will provide comparative data and allow the researchers to monitor progress over time. The researchers will also look at other factors that may influence the recruitment and retention of women scientists, such as the presence of women in top leadership roles, the rates at which tenured women stay in their positions, and equity in salaries across gender, race, and ethnicity.

“For my own work, I plan to begin to focus more on issues of intersectionality,” Jagsi concludes. “A particularly understudied area involves the career experiences in women with other minority identities, such as race. Further research is needed to understand the challenges these women face.”

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This study was supported by the Doris Duke Charitable Foundation and the New York Stem Cell Foundation Research Institute.

Cell Stem Cell, Beeler et al. “Institutional Report Cards for Gender Equality Results of a 4-Year Pilot to Encourage Benchmarking for Women in STEM.” https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30345-5