With a median overall survival rate of one year, metastatic sarcomas pose a substantial threat to patient wellbeing. Although current treatment plans include traditional therapies, such as radiation and chemotherapy, sarcomas’ multiple subtypes require more specific treatment.
Third-year resident Jeff Rytlewski, MD, is first author on two articles reviewing the barriers and prospects of sarcoma therapies. Under the mentorship of Varun Monga, MD, Rytlewski discussed photodynamic therapy and immunotherapy in Cancers and Annals of Translational Medicine, respectively.
Photodynamic therapy, a treatment that uses light to activate an inert photosensitivity, shows promising potential for treatment in sarcoma. Rytlewski and colleagues’ Cancers publication analyzes the ways in which photodynamic therapy is implemented in past studies. Their article suggests photodynamic therapy might be the future of treatment, considering traditional treatments lead to a relapse rate of 20–30% within three years.
Although radiation and local resection are common treatment methods, several studies suggest photodynamic therapy paired with verteporfin may hold more potential. Verteporfin regulates the Hippo pathway, a pathway that drives sarcoma cell death from oxidative stress and limits cell proliferation. Paired with photodynamic therapy, verteporfin could induce cell death and help reduce the rate of sarcoma relapse.
Annals of Translation Medicine Publication
Among other unique characteristics, sarcomas have fewer immune cells and are thus considered immunologically “cold.” As a solution, immunotherapy may not be very effective; mechanisms behind changing a sarcoma tumor microenvironment from a “cold” to a “hot” immunophenotype remains a topic of great scientific interest. In this article, Rytlewski, Monga, and Mohammed Milhem, MBBS, review clinical immunotherapy studies and explore possible solutions to improve the efficacy of immunotherapy; i.e., turning “cold” tumors “hot.”
In their analysis, the three found that a combination of immunotherapy and traditional treatments, like radiation, chemotherapy, and tyrosine kinase inhibitors, could treat common sarcoma subtypes. They also addresses treatments in their earlier trials such as photodynamic therapy, T cell therapies, and more.
Mentorship from Monga
After working on service with Monga, Rytlewski says the clinical assistant professor took him under his wing and brought him onto a verteporfin research project.
“He is incredibly patient as a mentor, allowing time for discussions on topics I don’t fully understand to better grasp the nuances of our projects which has helped going forward,” Rytlewski said. “He models excellent patient care; I frequently see him answer patient calls and beautifully handle the toughest conversations.”
Rytlewski also credits Monga with being a present and flexible mentor and physician.
“He’s helped me design my career, come up with post residency graduation plans, look out for upcoming conferences, calm nerves when things aren’t working out, and meet for dinner because COVID is tough and we needed a good night,” Rytlewski said. “It does mean a lot to have two publications, but that feels much more a by-product of being lucky. I’m much happier that I’ve found such an irreplaceable mentor.”