Personalized Medicine: The Future of Cancer Care?

Imagine knowing if a chemotherapy agent will be the most effective agent for a patient’s cancer before ever administering it. That is the future of cancer care and the aim of research underway at Cleveland Clinic Weston Hospital, reports Jorge Manrique-Succar, MD, Sarcoma Program Director for Cleveland Clinic in Florida.

Dr. Manrique-Succar is leading a team of Cleveland Clinic researchers working in collaboration with Florida International University’s Robert Stempel College of Public Health & Social Work to conduct precision medicine feasibility studies using drug sensitivity testing (DST) and genomic profiling to guide clinical decision-making.

Drug sensitivity testing

The collaboration entails taking tumor tissue obtained from Cleveland Clinic patients during standard-of-care diagnostic testing or scheduled surgery or biopsies and having them tested by a team at FIU for chemosensitivity to different drugs as single agents or in combinations. Next generation sequencing is also performed on tumor and germline tissue samples to correlate the genetic profile of the tumors with the response to the different chemotherapy agents.

Diana Azzam, PhD, a translational cancer researcher at the Robert Stempel College of Public Health & Social Work, is Research Director of FIU’s Center for Advancing Personalized Cancer Treatments. She leads the FIU team using a state-of-the-art viability assay designed for ex vivo high-throughput DST.

This type of testing allows researchers to rapidly assess how tumor cells respond to different chemotherapy agents outside the body, helping to identify the most effective treatments. “A scoring system also indicates if the effect is higher or lower when various agents are tested individually or in a combination,” explains Dr. Manrique-Succar.

Sarcoma-specific study

The Functional Drug Screening and Genomic Profiling in Advanced Sarcomas study is the first collaboration of the two teams. Funded by a $350,000 grant from the Scott R. MacKenzie Foundation and launched in 2021, the prospective, non-randomized observational study recruited 10 adult patients with confirmed or suspected relapsed or refractory sarcoma diagnoses from Cleveland Clinic’s Sarcoma Program at Weston Hospital.

“Sarcomas are rare, aggressive and typically harder to prevent, diagnose and treat than more common cancers,” states Dr. Manrique-Succar. “Our hope with this feasibility study is to determine if functional precision medicine has a role in adult sarcoma treatment.”

About 120 FDA-approved cancer drugs were tested in the study, including those currently used in sarcoma treatment and those outside of sarcoma treatment. Dr. Manrique-Succar notes there are only a few types of sarcomas – such as osteosarcoma, Ewing sarcoma and rhabdomyosarcoma – that have a clear indication for chemotherapy. “Because of the rarity of sarcomas, it is difficult to conduct clinical trials to test novel drug therapies for patients with other forms of sarcomas,” he says.

In this initial study, treating physicians were not provided DST results. Instead, they developed treatment plans independently based on standard-of-care options. Patients were then followed up to two years to assess their clinical outcomes, including response to therapy and progression-free survival.

Though not a treatment study, the researchers aim to correlate in vitro drug sensitivity results with treatment outcomes achieved with standard chemotherapy drugs.

“By also looking at in vitro tumor cell response to non-standard FDA-approved drugs, we hope to identify potential alternative treatment options for future study,” says Dr. Manrique-Succar. “This could one day mean faster, more effective treatments tailored to the unique tumor profile of patients with aggressive sarcomas.”

The study is currently in the analysis stage with results to be published later this year.

Expanding to other cancers

A second feasibility study, launched last year, expands upon the original sarcoma-focused study to include other forms of recurrent or refractory cancer, both solid tumors and blood cancers. The Individualized Treatments in Adults With Relapsed/Refractory Cancers study will enroll up to 36 patients from Cleveland Clinic in Florida with advanced cancers who do not have curative treatment options.

“We are already close to our enrollment goal and have study participants being treated for a variety of cancers, including melanomas, sarcomas, lung, breast and colon cancers, among others,” reports Dr. Manrique-Succar.

As in the sarcoma-specific study, DST and genomic screening are performed. However, in this trial, treating physicians receive a ranked list of therapeutic options with suggested doses and schedules based on a patient’s drug sensitivity scores. They then decide – although not the aim of the study – which treatment is most appropriate for each case.

“Our first goal is to demonstrate that it is feasible to provide timely treatment recommendations based on individual test results,” explains Dr. Manrique-Succar. “Then we want to compare outcomes of DST-guided therapy to conventional therapy.”

The study enrollment period is expected to be completed this year and patients will be followed for one-year post-treatment.

As these studies progress, they could pave the way for a new era of precision oncology, where treatment decisions are guided by real-time tumor response data, improving outcomes for patients with hard-to-treat cancers.