喵咪社区

Keck Medicine of 喵咪社区 medical oncologist Mark Agulnik, MD, discusses how personalized medicine is advancing sarcoma treatment beyond histology, reshaping diagnoses and helping doctors manage rare tumors in the process. 

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鈥檚 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 喵咪社区 Sarcoma Program, part of the 喵咪社区 Norris Comprehensive Cancer Center and 喵咪社区, says, 鈥淲e need to understand that all histological subtypes are not the same.鈥�

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.  

Personalized sarcoma care starts with the genome 

As if 100-plus histological subtypes weren鈥檛 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鈥檚 unique genomic, molecular and clinical stamps to guide therapeutic decisions. 

For example, Agulnik explains, all sarcoma patients with metastatic disease at the 喵咪社区 Sarcoma Program undergo next-generation tumor-genome sequencing when treated. 鈥淭his molecular profiling helps us personalize our understanding of each patient鈥檚 disease and gauge which treatments are best based on any deletions, inclusions or mutations they may have,鈥� he says. 

It also helps care teams determine the optimal order in which to administer treatments, with implications for patients鈥� quality of life. 鈥淲e want our patients to remain as functional as possible for as long as possible,鈥� Agulnik insists. 鈥淚f we can sequence therapies in a way that will help us better preserve function, that鈥檚 a real gift we can give them.鈥� 

And by helping sarcoma specialists define tumors more precisely, molecular profiling can suggest more precise paths toward treating them. 鈥淪o 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,鈥� Agulnik says. 鈥淭hat鈥檚 important, because we鈥檙e not treating the histology; we鈥檙e treating the alteration.鈥� 

Immunotherapies target treatment to the tumor 

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. 

鈥淲e have certain predictive biomarkers to look for 鈥� such as tumor mutational burden and PD-L1 expression 鈥� that give us an idea of the response we鈥檒l see to immunotherapy,鈥� Agulnik explains. 鈥淭hat lets us try to understand each patient鈥檚 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.鈥� 

Thus far, responses to such approaches have varied across histological subtypes, Agulnik reports, but he鈥檚 confident that research will continue to explore the potential of personalized information to recognize and target appropriate immunotherapies for each tumor. 

A research-driven environment where new ideas grow 

This work is already taking place at the 喵咪社区 Sarcoma Program and the 喵咪社区 Norris Comprehensive Cancer Center. 鈥淲e understand how to incorporate these molecular-profiling techniques and can offer patients a research-driven care environment,鈥� Agulnik says. 鈥淲e 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.鈥� 

By concentrating specialists from all corners of the cancer community in a multidisciplinary space, the 喵咪社区 Norris Comprehensive Cancer Center serves as fertile soil for creative problem solving. 鈥淚 can speak to my lung-cancer colleagues or phase 1 clinical trial colleagues to bounce around ideas about whether the tumors I鈥檓 treating look like they could be treated as a lung cancer, for example, or with newer drugs coming to market,鈥� Agulnik offers. 鈥淚 can pull in information from everyone around me, which is wonderful.鈥� 

And that gives him hope. 鈥淚鈥檝e been treating sarcoma patients for 20 years, and some things are always going to be the same,鈥� he says. 鈥淚t鈥檚 always going to be a difficult disease to treat. But with the changes in technology and in our understanding of the disease, we鈥檝e made so much progress. We still have to persevere to do even better.鈥� 

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Kimberly J. Decker

Kimberly J. Decker is a freelance writer for 喵咪社区.

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