Month: March 2023

Originally published on Illumina News Center

“Pediatricians like to say children are not little adults, and accordingly, pediatric cancer is not just the miniature form of adult cancer,” says Midhat Farooqi, MD, PhD, Director of Molecular Oncology, Genomic Medicine Center at Children’s Mercy Kansas City in Missouri. Historically, less attention and expertise have been devoted to researching cancer in children than adults, but Children’s Mercy is helping lead the effort to change that.

From its humble beginnings in 1897 with just one bed, the hospital has grown to 390 inpatient beds and 16 locations. It had 14,345 pediatric admissions in 2022—60% of them for patients less than 10 years old—who traveled to the hospital with their families from all 50 US states.

Children’s Mercy also pursues leading-edge research. In 2015, it established the Children’s Mercy Research Institute, founded and led by Tom Curran, PhD, FRS, Senior Vice President, Executive Director, Chief Scientific Officer, and Donald J. Hall Eminent Scholar in Pediatric Research. The Institute supports the launch of ambitious initiatives like Genomic Answers for Kids (GA4K), headed by Tomi Pastinen, MD, PhD, Dee Lyons/Missouri Endowed Chair in Pediatric Genomic Medicine.

The program’s goal is to sequence 30,000 children and their parents, and it just passed the milestone of providing more than 1,000 rare disease diagnoses to families; it largely addresses cases of rare genetic disease, but, as Farooqi points out, “Pediatric cancer is also a rare disease,” and the program is enrolling cancer patients as well.

Currently, the hospital is conducting 137 studies and trials—49 of which are in oncology—and developing databases that are crucial for research. In 2017, Erin Guest, MD, Director of the Children’s Mercy Cancer Genomics Program, and Alexander Kats, MD, Director of Nephropathology and Transplantation Pathology Services, set up a pediatric oncology biobank for storing both solid tumor and leukemic samples. This biobank is now part of the Research Institute’s CAP-accredited Biorepository, which is overseen by John David Nolen, MD, PhD, Chair of the Department of Pathology and Laboratory Medicine.

To date, over 500 patients have enrolled and Farooqi and his team have performed whole-genome and whole-exome sequencing on 200 of them. Children’s Mercy, which is the pediatric consortium partner of The University of Kansas Cancer Center, was awarded a grant from the National Cancer Institute to share this genomic data as part of the Childhood Cancer Data Initiative. Farooqi explains, “Collecting and sharing data nationally and beyond is really important for pediatric cancer because the numbers are low—it can take a few years for the university to register a dozen children with a single tumor type, whereas for adults, let’s say, the same number of cases could be accrued within a month. If we all work together, we can amass higher numbers of rare tumor types within pediatrics as well.”

How is pediatric cancer different from cancer in adults?

Cancer in children is rare, making it more difficult to study.Genetic mutations differ in pediatric cancer patients compared to adults—even within the same tumor type.Pediatric cancer is driven more often by genetic fusions than genetic mutations, necessitating the development of different targeted therapies.The younger the patient, the more years side effects from chemotherapy could potentially affect them.

Not only does the study and diagnosis of cancer differ with children, but their treatment is more complex, considering how much of their life still lies ahead. This raises the stakes considerably. “Nonpersonalized, general chemotherapy is sort of a poison for all cells,” Farooqi cautions. “It hits cancer cells first because they are dividing faster, but normal cells are also affected, which leads to side effects and sometimes even secondary cancers from the initial therapy itself. We have to be really mindful that after cancer treatment, kids have a much longer lifetime ahead of them, so developing precision therapies that don’t have off-target effects is much more important in pediatrics.”

Farooqi works in the lab with Assistant Clinical Laboratory Director Lisa Lansdon, PhD, who helps the team look for clinically actionable variants. Her motivation stems from her first encounter with pediatric rare disease and pediatric cancer: When she was in elementary school, a friend was diagnosed with an inherited blood disorder called Diamond-Blackfan anemia. “He ended up passing away in sixth grade after developing leukemia,” she says. “It was a really impressionable experience for me, and I knew that genetics was where I wanted to land.”

Farooqi, too, was inspired by a personal connection. While he was in his residency, his grandfather was diagnosed with cancer. “That made me see the value of genetic testing for oncology,” he says. “Because one of the things we’re finding is that every patient’s cancer is unique, and that there are many, many different roads that a cell can take to become a tumor cell. So, figuring out which path that is can have a really big impact on the diagnosis, prognosis, and treatment for every patient with cancer.”

Why do kids get cancer?

For the most part, the answer to this question is unknown. Relative to adults, children have had much less exposure to environmental toxins and less time to accumulate “somatic mutations,” which generally occur after birth and can lead to cancer. We know that 10%–15% of all childhood cancers occur because of a predisposition—they carry a “germline mutation,” usually inherited from a parent at conception, that gives them a higher risk of cancer in their lifetime. However, this is not much different from the rate of adult cancers stemming from germline mutations, which is thought to be 5%–10%. Overall, more research is needed to answer this question.

A new exome test for patients 
Recently, Children’s Mercy launched a clinical exome-based test for newly diagnosed or newly relapsed pediatric oncology patients. The Genomic Medicine Center’s CAP- and CLIA-certified lab runs the exome-based sequencing test at 300× coverage on samples of the patient’s tumor tissue and their healthy tissue (also called tumor/normal testing), analyzing the former for somatic variants and the latter for germline variants.

The advantage of doing this paired tumor/normal testing is that it tells the clinical team which specific variants are present in the tumor—if the healthy tissue also has the variant, then the patient’s blood relatives may benefit from being tested as well. “Otherwise, for some variants you always have this question of, ‘Is this variant in the germline?’” Farooqi says. “And if you’re trying to target mutations only in the tumor, then it helps to be absolutely sure that the variant is somatic.”

In general, most adult reference laboratories tend to do a high volume of tumor-only testing. Some academic institutions and commercial labs will do paired tumor/normal testing, but it’s more the exception than the rule. Children’s Mercy tests both under one roof and also offers a paired germline variant report, all thanks to an enormously supportive clinical group, hospital administration, and the philanthropic community of Kansas City.

“We’re lucky to have the support of the Hematology/Oncology group, under the direction of Alan Gamis, MD, MPH, and the Genetics Division of Pathology, directed by Carol Saunders, PhD,” says Farooqi, “and financial help from local foundations such as Black & Veatch, Big Slick, Braden’s Hope for Childhood Cancer, as well as many others. Plus, our hospital’s Philanthropy department and Senior Vice President of Allied Health Brian O’Neal, PharmD, MS, created a framework to ensure that no patient at Children’s Mercy would have to pay out of pocket for this testing, which is amazing!”

A bright future 
Farooqi, who joined the hospital in 2016, is thrilled to be offering the exome-based test with a quicker turnaround mode of operation and the opportunity to share data for research. “Time is of the essence for our patients with cancer, so having accelerated capabilities to do paired tumor-normal analysis clinically in real time, plus the accuracy of the variant calling, makes the integration of our NovaSeq 6000 with Illumina Connected Software critical to our workflow,” he says. “Since we’ve laid a foundation, I am now most excited about getting to grow the program to offer more research insights and clinical tests—we are keenly interested in analyzing the sequence data for microsatellite instability and tumor mutational burden, as well as pharmacogenomics, to look at variants that could impact dosing for chemotherapy medicines.”

“We can see a path toward the future,” Lansdon adds. “We’re going to be able to develop additional tests that we can layer on top, get better insights, and give the latest and greatest information to our clinical teams. We have a laundry list a mile long of all the things that we could do in this vision for the future, and that’s super exciting, because it means that it doesn’t stop here with our new clinical exome test. For us, it really is just the beginning.”

Learn more about how Illumina is expanding access to genomics, click here.

One of Cisco’s Leadership Expectations is that they Make the Future, which includes championing diversity and inclusion with sponsorship. Since The Multiplier Effect (TME) launched in 2017, Cisco has consistently advocated for sponsorship as a powerful tool that leaders can use to connect, advocate, and accelerate the careers of diverse talent. By taking the TME pledge, leaders can sponsor someone different from themselves and commit to helping support their career advancement.

The Power of Sponsorship.

Today, a large racial gap in corporate spaces does not afford many Black employees’ equitable access to leadership roles. We know having a diverse workforce leads to better innovation, performance, and work efficiency. However, Black employees comprise only 14% of all US employees, accounting for only 7% of managerial roles. While some may view this as just another statistic, Derek Idemoto, Senior Vice President – Corporate Strategy, and Jerome J. Sanders, Product Marketing Manager – Emerging Technologies & Incubation (ET&I), view this as an opportunity to make long-lasting change. We recently had the privilege of connecting with them to discover how they “Power an Inclusive Future” for one another through sponsorship.

Sponsoring Across Difference.

Tell us briefly about yourself.

Derek (He/Him/His): I’m a third-generation Japanese American, and I grew up in San Jose, California, so the apple didn’t fall too far from the tree in joining Cisco a little over 15 years ago. My heritage has taught me how vital resilience, stamina, and hard work are, both personally and professionally, in the face of extraordinary challenges that Japanese Americans faced during and after World War II. Currently, I lead our Corporate Development and Cisco Investments team, which helps drive innovation and growth for Cisco through investments and acquisitions.

Jerome (He/Him/His): I am a Product Marketing Manager in Cisco’s Emerging Technologies and Incubation team. I was born and raised in San Diego, California, by two United States Navy Veterans, and I currently reside near the Research Triangle Park in Cary, North Carolina. I am the first in my family to achieve a college degree (from Santa Clara University Leavey School of Business) and the first to pursue a career in tech. In my spare time, you can catch me serving as Chairperson for First Tech Fund, training for my upcoming 70.3 Chattanooga Ironman Triathlon, or roaming the world with my “do not disturb” button on.

Sponsorship requires leaders to use their social capital to propel their sponsee’s career. How has Derek done this for you? 

Jerome: Derek’s sponsorship is one of the many reasons I see myself at Cisco for many years as a leader, shareholder, and champion for the future we are building together. Aside from our monthly 1:1 meeting, Derek has spoken directly to Executive Leadership Team members, his peers in my organization, and my manager about how I show up at Cisco. He is intentional in helping my leaders understand my career goals and how we can all work together to make them happen. Derek has also offered to shadow me in one of my team meetings to see how I lead and help me better learn how to “read the room” so I can build up my emotional intelligence and better serve my teams. This is what sponsorship means!

Some obstacles prevent Black employees from benefitting from sponsorship in the same way others might. What are some of the gaps you would like leaders to know about advocating for emerging Black leaders?

Jerome: Cisco leaders are not always proximate to emerging Black leaders on their teams. I challenge leaders to do a quick scan in the directory and see how far removed they are from an emerging Black leader in their group. An immediate action a leader can take to advocate for an emerging Black leader is to have regular skip-level meetings with them and become immersed in one another’s goals and aspirations. Proximity enables empathy and empathy enables sponsorship.

In performance reviews, sharing specific, actionable feedback on ways emerging Black leaders can improve is imperative. Avoid using language such as “aggressive,” “emotional,” “unapproachable,” or “lacking executive presence,” which generally elicits subjective feedback. Concrete feedback along with objective reviews can lead to higher performance reviews for emerging Black leaders, resulting in more sponsorship within this community.

Sponsorship is a mutually beneficial relationship for both the sponsor and sponsee. What have you learned from each other that you will carry forward?

Derek: I have learned that there are many paths to success, and it is important to find one that is authentically yours. With Jerome, I find that the reverse mentoring aspects of our relationship are more potent than the forward mentoring takeaways. How we show up for one another matters, so actions speak louder than words. Jerome once shared that when he met our CEO, Chuck Robbins, he was struck by something Chuck said about how it is always about the team. It is not just about us. Always give credit to others. Jerome said, “Nothing here at Cisco is done here alone.” Relationships, networking, and people, in general, are so meaningful.

Jerome: Given that both Derek and I are major sports fanatics, I love that Derek consistently shares, “Play the long game.” It is a reminder that our careers are not about the sprint ahead of us or short-term gains, but rather, seeing the bigger picture and appreciating how it all comes together with time. The best things in life take time. Many of us can carry this forward as we drive a business impact, while also living purpose-driven lives that create an inclusive future for all.

How we sponsor today directly impacts the type of leaders that will lead in the future. Derek, what qualities make a good leader, and what advice do you have for leaders looking to sponsor individuals whose identities differ from their own?

Derek: In my mind, there are five key qualities that leaders must have to apply to their sponsorship responsibilities:

Good decision-making skills are paramount – I believe in prioritizing decisions that place Cisco first, the team second, and self third.Recognize the difference between hard work and results – Leaders must recognize the importance of the “what” (the execution of the task and results) and the “how” (the approach taken to complete the task).Managing people is a “one-size fits one”, not all – Leaders must understand and be sensitive to each team member as a unique individual.Hire for traits and train for skills – One of my career and life sponsors, Ko Nishimura, former CEO and Chair of Solectron and fellow Japanese American, passed this valuable piece of advice.Details matter – Details often provide the data needed to support your positions and perspectives that can ultimately influence outcomes.

Jerome, what advice would you give to early-in-career Black tech professionals?

Jerome: I heard Dr. Cornel West share, “You have to use your status and power to be in service to others.” This rings true on so many levels when it comes to the need for sponsorship for underrepresented communities, especially historically disadvantaged Black and brown communities. Anytime I mentor any professional, I am intentional about asking my mentees to pay it forward. It is not enough to have a seat at the table unless we are willing to pull up another chair and ensure that it is accessible for someone else to sit in and thrive. The more we pay it forward, the more we can be of service to others.

Be the Change. Make the Impact.

Did you know: Seventy percent of sponsors are more likely to select a sponsee that looks like them. This behavior creates a homogenous sponsorship experience that will continue to benefit those of privilege and negatively impact people from underrepresented communities. Unlike traditional sponsorship methods, TME seeks to change that experience by strongly encouraging sponsors to step outside of their comfort zone. Currently, 70% of Cisco sponsees have two or more dimensions of difference from their sponsor globally!

Cisco’s commitment to fostering intentional relationships between sponsors and sponsees begins with leaders. Take the pledge to sponsor diverse talent today! Not sure where to start but want to make an impact? Click here to contact the TME team.

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