is there any breakthrough in sight?


Among the rarest forms of cancer, sarcomas develop in the bones and connective tissues that support structures in the body such as blood vessels, nerves and joints. This year, about 13,400 new cases of soft tissue sarcoma estimated to be diagnosed in the US alone, according to the American Cancer Society. As July marks Sarcoma Awareness Month, let’s take a look at why sarcomas are difficult to treat and how the latest advances in research can address today’s challenges.

This cancer is said to form when bone and soft tissue cells have mutations in their DNA – for reasons, like other types of cancer, that are not yet understood – that cause cells to develop into cancer cells, multiplying in an unregulated way. Eventually, these cells form a tumor, invading the surrounding healthy tissue.

Why are sarcomas difficult to treat?

For many years, anticancer drugs such as doxorubicin, halaven and imatinib, as well as radiotherapy, which can shrink tumors, making them easier to remove before surgery, have been considered the current standard of care for sarcoma. But breakthrough drugs have yet to be found.

This could partly be because sarcomas are so difficult to treat, for four main reasons. First, because there are more than 80 subtypes of sarcoma, it is difficult to develop a treatment that can treat all of these sarcoma types singly. According to Ryan Davies, chief executive officer (CEO) of US-based immunotherapy company CancerVAX, developing a one-size-fits-all treatment approach is challenging.

Second, because they are a relatively rare type of cancer, accounting for 1% of all adult cancers and 15% of childhood cancers, they are quite difficult to treat. This is because, like most rare diseases, there is often a lack of knowledge as well as available data regarding the prevalence of sarcomas, making it rare hard to convince pharmaceutical companies to spend on research and clinical trials that will have much smaller cohorts of patients. While the US Food and Drug Administration (FDA) came up with orphan drug designations for faster drug authorization for rare diseases to address this problem, only about 5% of rare diseases currently have treatments.

In addition, sarcomas can metastasize and spread to other parts of the body even after the primary tumor has been treated. Because sarcomas are usually locally aggressive, some tend to reappear in the same area, while others develop in a new location.

Davies also explained that sarcomas often appear with non-specific symptoms. This makes them hard to detect, which can lead to a delay in diagnosis. While time is of the essence for rapidly metastatic forms of cancer, for sarcomas like Ewing’s, which can mimic other types of cancer, the diagnosis is not easy. Imaging tests such as ultrasound and magnetic resonance imaging (MRI) are not always accurate, and most often, a biopsy is best done.

Recent breakthrough in Ewing’s sarcoma research: uncovering LINGO1 as a promising drug target

To expand treatment options for the treatment of Ewing’s sarcoma, CancerVAX is developing drugs that can kill tumors. Ewing’s sarcoma is often associated with cancer that begins in the bones of the legs, spine, and pelvis, and usually affects children and adolescents. Considered extremely rare, it affects one in a million people, and accounts for approx 1% of all childhood cancers.

Recently, LINGO1 protein was discovered as a biomarker as well as a drug target for Ewing’s sarcoma. Proteins acts as a gate protein, which is capable of binding to drugs targeted at destroying cancer cells. The CancerVAX immunotherapy approach aims to harness the potential of drug targets LINGO1 to treat this disease, because its protein is present on the surface of more than 90% of Ewing’s sarcoma tumors. The company is developing chimeric antigen receptor (CAR) T cells and bispecific antibodies designed to target LINGO1, using immune cells and tumor cells that have been harvested from patients with Ewing’s sarcoma.

“Ewing’s sarcoma is a rare disease that primarily affects children and adolescents. Because there have been no breakthroughs with new drugs and because the mortality rate is so high, the potential impact of Ewing CancerVAX’s treatment of sarcoma can be enormous in helping to save lives. Current therapies for Ewing’s sarcoma have peaked over the last few decades, and there is an urgent need for better outcomes. Approaches targeting chemotherapy-resistant tumors, especially in the setting of metastatic and/or microscopic residual disease would be revolutionary,” said Davies.

Collaborating with researchers at the University of California, Los Angeles (UCLA), the Ewing CancerVAX sarcoma program is making headway, having created seven candidate monoclonal antibodies, six of which have been fully humanized and assigned to target affinity for the LINGO1 protein. The company is looking to further advance preclinical studies, and investigate the safety and efficacy of drug candidates by 2024. “We hope this will inform our research allowing us to begin discussions with the FDA for clinical trials,” said Davies.

“CancerVAX is extremely encouraged by the progress we have made developing a sarcoma drug candidate. We believe in collaboration and hope our research can inform our own and with other companies’ additional drug development efforts,” said Davies. “We are leveraging other sarcoma research that has been done and hope our research can inform others in the future.”

FDA clears sarcoma therapy

Another company making headway in the treatment of Ewing’s sarcoma is Sumitomo Pharma Oncology’s clinical stage biopharma, headquartered in Cambridge, Massachusetts. Currently in phase 1 trials, the company recently announced that its drug candidate TP-1287 was granted orphan drug designation by the US FDA.

TP-1287 is an orally administered CDK9 inhibitor that was found to downregulate the transcription of certain genes. As a prodrug of the CDK9 kinase inhibitor alvocidib, it is hydrolyzed to produce alvocidib, which then binds to CDK9 to inhibit its phosphorylation. This leads to reduced messenger RNA (mRNA) in genes such as c-MYC and myeloid cell leukemia-1 (MCL-1) and inhibited transcription, resulting in apoptosis – which is a type of programmed cell death.

The candidate was previously granted a rare childhood disease designation from the FDA. This is the title given to drugs that treat life-threatening manifestations that affect patients from birth to 18 years of age.

Meanwhile, California-based genome writing company Replay’s partnership with The University of Texas MD Anderson Cancer Center (MD Anderson), which gave rise to the oncology-focused company Syena, has developed engineered cell therapies for the treatment of synovial sarcoma and myxoid/round cell liposarcoma – both of which affect the limbs. NY-ESO-1 TCR/IL-15 NK cell therapy comprises cord blood-derived natural killer cells that can express an affinity-enhanced T-cell receptor (TCR) targeted against the cancer-associated antigen NY-ESO-1. Since this antigen is highly immunogenic and is expressed on many types of cancer cells, this makes it a promising immunotherapeutic target.

The FDA issued a ‘safe to proceed’ letter to the company’s Investigational New Drug (IND) application for NY-ESO-1 TCR/IL-15 NK last month. The company is currently investigating the drug’s effectiveness in a phase 1/1b study in which the drug will be administered after chemotherapy to patients. The clinical trial, which will begin later this year, will enroll 44 sarcoma patients.

As biotech steps up their therapeutic research, such as London-based clinical stage company Avacta, which received orphan drug status for the chemotherapy drug doxorubicin AVA6000 for soft tissue sarcoma last year, treatment options are expanding. And the fact that this hard-to-diagnose disease quickly metastasizes and is lethal, demands more research into drug development.

IN SECTION Logo 960x960px Web 72ppi Transparent Thin Border

New technologies related to sarcoma research


Source link

Related Articles

Back to top button