Sumitomo Pharma gets an appointment for the treatment of Ewing’s sarcoma
Sumitomo Pharma Oncology, Inc., a clinical stage company focused on new cancer therapies, said the US Food and Drug Administration (FDA) had granted the orphan drug designation for TP-1287, an investigative oral CDK9 inhibitor, for the treatment of Ewing’s sarcoma.
“We are pleased to have received this designation for TP-1287 which underscores the need for additional treatment options for patients with Ewing’s sarcoma,” said Patricia S. Andrews, chief executive officer and global head of oncology, Sumitomo Pharma Oncology, Inc.
“We recognize the unmet need for new treatments in this disease condition and are excited to contribute to the advancement of this research with the goal of helping improve patient outcomes.”
Ewing’s sarcoma is a rare type of cancer that occurs in the bones or in the soft tissue around the bones. This disease occurs when cells undergo DNA changes that cause cells to multiply rapidly, producing tumors of abnormal cells that are capable of invading and destroying healthy body tissue. Abnormal cells can break off and metastasize throughout the body. Ewing’s sarcoma can occur at any age, but is more common in children and adolescents.
“TP-1287 showed strong inhibition of intracellular kinases including CDK9. CDK9 inhibition leads to downregulation of key antiapoptotic proteins such as MCL-1, which in turn has been shown to inhibit tumor growth in preclinical models of hematological malignancies and several tumor types,” said Jatin J. Shah, chief medical officer at Sumitomo Pharma. Oncology.
TP-1287 was also given a rare childhood disease designation from the FDA for the treatment of Ewing’s sarcoma. Rare pediatric diseases are serious or life-threatening diseases in which serious or life-threatening manifestations primarily affect patients from birth to 18 years of age.
TP-1287 is currently being evaluated in phase 1, the first human study of oral TP-1287 in patients with metastatic or advanced progressive solid tumors that are refractory to, or intolerant to, established therapies that are known to provide them with clinical benefit. conditions, which are being carried out in the US
About Sumitomo Pharmacy TP-1287 Oncology
TP-1287 is the investigated oral phosphate prodrug of the CDK9 inhibitor alvocidib. TP-1287 is enzymatically hydrolyzed to yield alvocidib. Alvocidib binds at the ATP-binding site of CDK9, stopping its phosphorylation by CDK9.
This binding prevents productive transcription and causes reduction of messenger RNA (mRNA) in genes such as c-MYC and MCL-1.
Downregulation of c-MYC and MCL-1 transcription causes apoptosis in various tumor cells.
Spanish Ewing sarcoma research
Ewing’s sarcoma is caused by a single oncogene resulting from the fusion of two genes. Although a variety of genes may be involved, EWSR1 and FLI1 and the resulting cancer-promoting oncogene, EWS-FLI, were found to be responsible in the majority of patients.
Driven by the need for a genetically traceable model with which to study this disease, the researchers led by Cayetano González, ICREA research professor at IRB Barcelona in Spain, and Jaume Mora, scientific director at SJD Pediatric Cancer Center Barcelona (PCCB) , recently engineered Drosophila (genus of small flies) transgenic strains expressing a mutant variant of a human oncogene called EWS-FLIFS.
They found that expression of the human EWS-FLIFS protein in certain Drosophila cell types triggers the same oncogenic pathway known to be responsible for the oncogenic activity of EWS-FLI in human patients.
Scientists hope their studies can produce compounds that can serve as key molecules for the development of therapeutic drugs against the disease.