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Originally published April 2, 2026
Last updated April 2, 2026
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Sarcomas are notoriously difficult cancers to treat. Their rarity, aggression and heterogeneity have complicated care and confounded attempts at developing breakthrough therapies for generations.
Historically, standard treatments relied largely on a histologically based classification system in which a tumor’s subtype would dictate therapeutic options. But with more than 100 distinct histological subtypes now identified, Mark Agulnik, MD, a medical oncologist and co-leader of the USC Sarcoma Program, part of the USC Norris Comprehensive Cancer Center and Keck Medicine of USC, says, “We need to understand that all histological subtypes are not the same.”
Nor should all sarcoma treatments be the same. Thus Agulnik explains how advances in personalized medicine are helping sarcoma specialists tailor treatment to the patient.
As if 100-plus histological subtypes weren’t enough, sarcomas even within the same subtype can display different molecular drivers, clinical behaviors and treatment responses, Agulnik says. The advantage of personalized medicine is that it lets clinicians leverage data about a tumor’s unique genomic, molecular and clinical stamps to guide therapeutic decisions.
For example, Agulnik explains, all sarcoma patients with metastatic disease at the USC Sarcoma Program undergo next-generation tumor-genome sequencing when treated. “This molecular profiling helps us personalize our understanding of each patient’s disease and gauge which treatments are best based on any deletions, inclusions or mutations they may have,” he says.
It also helps care teams determine the optimal order in which to administer treatments, with implications for patients’ quality of life. “We want our patients to remain as functional as possible for as long as possible,” Agulnik insists. “If we can sequence therapies in a way that will help us better preserve function, that’s a real gift we can give them.”
And by helping sarcoma specialists define tumors more precisely, molecular profiling can suggest more precise paths toward treating them. “So as opposed to saying that the patient has a leiomyosarcoma or a synovial sarcoma, we can say that the patient has an NTRK fusion sarcoma, or an ALK-rearranged sarcoma,” Agulnik says. “That’s important, because we’re not treating the histology; we’re treating the alteration.”
While immunotherapies have transformed cancer care overall, very few have received approval for use in treating sarcoma. But here, too, personalized medicine is changing the game.
“We have certain predictive biomarkers to look for — such as tumor mutational burden and PD-L1 expression — that give us an idea of the response we’ll see to immunotherapy,” Agulnik explains. “That lets us try to understand each patient’s immune signature to better identify those who may benefit from immune checkpoint inhibitors or combination strategies that use, perhaps, a tyrosine kinase inhibitor or a chemotherapy with a checkpoint inhibitor.”
Thus far, responses to such approaches have varied across histological subtypes, Agulnik reports, but he’s confident that research will continue to explore the potential of personalized information to recognize and target appropriate immunotherapies for each tumor.
This work is already taking place at the USC Sarcoma Program and the USC Norris Comprehensive Cancer Center. “We understand how to incorporate these molecular-profiling techniques and can offer patients a research-driven care environment,” Agulnik says. “We have an incredible developmental-therapeutics department with phase 1 trials that our patients can access. At the same time, our robust, comprehensive teams of translational researchers are bringing drugs to clinician teams, and clinical scientists are making headway with respect to new drugs, new combinations and other therapies.”
By concentrating specialists from all corners of the cancer community in a multidisciplinary space, the USC Norris Comprehensive Cancer Center serves as fertile soil for creative problem solving. “I can speak to my lung-cancer colleagues or phase 1 clinical trial colleagues to bounce around ideas about whether the tumors I’m treating look like they could be treated as a lung cancer, for example, or with newer drugs coming to market,” Agulnik offers. “I can pull in information from everyone around me, which is wonderful.”
And that gives him hope. “I’ve been treating sarcoma patients for 20 years, and some things are always going to be the same,” he says. “It’s always going to be a difficult disease to treat. But with the changes in technology and in our understanding of the disease, we’ve made so much progress. We still have to persevere to do even better.”
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