Sylvester K12 Symposium Brings Together Prior and New Award Winners

Scholars share their work tackling some of the most intractable diseases, and welcome career advice

On March 18, the 2022 Sylvester K12 Calabresi Symposium was held virtually from Sylvester Comprehensive Cancer Center. The half-day symposium, led by Alan Pollack, M.D., Ph.D., chair of the Department of Radiation Oncology, provides current Sylvester K12 awardees the opportunity to showcase their research to date, get feedback from internal and external clinical oncology leaders, and ask questions of past K12 winners further along in their career paths.

Sylvester is one of only 22 sites across the country in the K12 program, whose purpose is “to provide institutional career development awards designed to prepare newly trained clinicians who have made a commitment to independent research careers, and to facilitate their transition to more advanced support mechanisms.” Through the K12 grant, the National Cancer Institute provides salary and research support for two junior faculty scholars per year, and Sylvester supports at least one additional scholar. This year’s symposium highlighted the work of these physician-scientists.

Yael Mossé, M.D., the Patricia Brophy Endowed Chair in Neuroblastoma Research at the Pereleman School of Medicine, was the keynote speaker. Dr. Mossé has devoted her career to finding therapies for childhood cancer. She discovered and elucidated the role of anaplastic lymphoma kinase (ALK) in most patients with the inherited form of neuroblastoma. This work has led to a broad characterization of the functional consequences of ALK mutations and the development of ALK inhibitors. One these, lorlatinib, has entered the phase 3 trials and could receive regulatory approval if a substantial improvement in cure rates is observed.

“As you move ahead in drug discovery research, I recommend you engage early with the FDA, and be sure you have rigorous preclinical modeling to support your proposed clinical trials,” Dr. Mossé said. “Be looking ahead, [and] try to develop an infrastructure to rapidly translate leads into effective therapies.”

Scholarly Work

Second-year scholar Daniel O’Neil, M.D., M.P.H., described his work studying drivers of survival disparities between patients with breast cancer living with and without HIV. He reported interim findings on populations in the Miami area and in South Africa, where the prevalence of HIV in women is highest in the world. “My time through residency and fellowship has been spent overseas working on global health care delivery interventions, prompting this interest,” O’Neil said.

Hematologist Terrence Bradley, M.D., is focused on targeting lysine-specific demethylase 1 (LSD1) in myeloid neoplasms. Dr. Bradley, also a second-year scholar, is enrolling phase 2 trial participants to test the LSD1 inhibitor bomedemstat, which has been effective in some other blood cancers, for polycythemia vera and essential thrombocythemia patients who have not responded to at least one standard therapy. “Based on studies in myelofibrosis, we expect to see significant improvements in hematologic control and symptom burden in these patients,” he said. “These patients have limited FDA-approved options, so novel, well-tolerated and effective therapies are needed.”

First-year scholar Janaki Sharma, M.D., is launching a pilot study on castrate-resistant prostate cancer from failed androgen-deprivation therapy. “These are patients who may experience remission, but will at some point have disease progression if they live long enough,” she said. She is working on the role of nitric oxide signaling during the progression to castrate-resistant disease.

Hematologist Namrata Chandhok, M.D., also a first-year scholar, is addressing an unmet need for new therapies in acute myeloid leukemia and myelopdysplastic syndrome. She is currently enrolling for a proof-of-concept biomarker-driven trial of olaparib, a PARP inhibitor, on IDH1/2 mutant relapsed/refractory patients, and performing preclinical studies on defective DNA damage response in myeloid malignancies to identify optimal therapeutic combinations for these patients. “We are looking to expand on this project by leveraging cancer-specific vulnerabilities such as micronutrient deficiencies in malignant cells with the Cimmino Lab [at UM],” she said.

Another first-year scholar, Trent Wang, D.O., M.P.H., who works in transplantation and cellular therapy, is homing in on prevention and prognostication of graft-versus-host-disease (GVHD) after hematopoietic stem cell transplant (HSCT). “This is an urgent need, given that over half of all HSCT recipients develop this condition and lack a durable response to corticosteroid therapy,” Dr. Wang said. Using the divisional biobank, he is validating soluble prognostic biomarkers in patients with among the most complex transplants: those with mismatched unrelated grafts.

The two recipients of 2022 K12 awards are Katherine Amin, M.D., and Benjamin Diamond, M.D.

Dr. Diamond, a hematologist/oncologist, will focus his K12 research on using a quadruplet drug therapy to salvage deep responses in relapsed/refractory multiple myeloma patients who missed the opportunity for an upfront quadruplet. “At a referral center like UM, we feel this will be especially impactful at providing patients with well-tolerated and highly active therapies that they otherwise would not have had access to,” Dr. Diamond said.

Dr. Amin, a urologist with a fellowship in female pelvic medicine and reconstructive surgery, will research the pathophysiology of the effects of aromatase inhibitor (AI) medication on the genitourinary microbiome and inflammation in women with a history of breast cancer. “We hope to characterize host-microbiome alterations and their association with decreased quality of life and bothersome side effects and improve adherence to life-extending therapy in women with breast cancer,” Dr. Amin said.

Following the K12 scholar presentations were informal talks with four prior K12 scholars: Jacob Scott, M.D., D.Phil, associate professor and staff physician-scientist at the CWRU School of Medicine and Cleveland Clinic; Douglas Johnson, M.D., associate professor of medical oncology at Vanderbilt University Medical Center; Aaron Mansfield, M.D., professor of oncology at Mayo Clinic; and Neha Goel., M.D., assistant professor of surgery at the University of Miami Health System.

Several of these panelists shared their unique paths to directing their own labs. They offered advice on the pros and cons of joining an NCI cooperative group, how to ensure protected time for research, and the changing role of mentors as their careers have matured. Panelists encouraged the researchers as they embark on their inevitable “funding odysseys,” counseling them to persevere beyond the grant rejections and continue to make those “shots on goal” that will, eventually, pay off.

Tags: Dr. Alan Pollack, Dr. Benjamin Diamond, Dr. Daniel O’Neil, Dr. Janaki Sharma, Dr. Katherine Amin, Dr. Namrata Chandhok, Dr. Terrence Bradley, Dr. Trent Wang, Sylvester Comprehensive Cancer Center, Sylvester K12 Calabresi Symposium