TP53, MDM2 Alterations Linked to Cisplatin Resistance in GCT

This article originally appeared here.
Share this content:
<i>TP53</i>, <i>MDM2</i> Alterations Linked to Cisplatin Resistance in GCT
TP53, MDM2 Alterations Linked to Cisplatin Resistance in GCT

FRIDAY, Sept. 23, 2016 (HealthDay News) -- In germ cell tumors (GCTs), TP53 and MDM2 alterations correlate with cisplatin resistance and are associated with inferior outcome, according to a study published online Sept. 19 in the Journal of Clinical Oncology.

Aditya Bagrodia, M.D., from the Memorial Sloan Kettering Cancer Center in New York City, and colleagues identified a genetic basis for cisplatin resistance among men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue. The investigators performed whole-exome sequencing or targeted exon-capture-based sequencing on 180 tumors. Using a combination of post-chemotherapy parameters, patients were classified as cisplatin sensitive or resistant.

The researchers found that TP53 alterations were only seen in cisplatin-resistant tumors, and were especially common among primary mediastinal nonseminomas (72 percent). Patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model more often had TP53 pathway alterations, including MDM2 amplifications. Independent of the IGCCCG model, TP53 and MDM2 alterations predicted adverse prognosis. Fifty-five percent of cisplatin-resistant GCTs had actionable alterations, including novel RAC1 mutations.

"A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies," the authors write. "Genomic profiling of patients with advanced GCT could improve current risk stratification and identify novel therapeutic approaches for patients with cisplatin-resistant disease."

Several authors disclosed financial ties to the pharmaceutical industry.

Abstract
Full Text (subscription or payment may be required)

Share this content:

is free, fast, and customized just for you!

Already a member?

Sign In Now »

Drug Lookup

Browse drugs by: BrandGenericDisease

Trending Activities

All Professions



Sign up for myCME e-newsletters


More in Home

Factors ID'd to Predict Fatty Liver in Obese Teens

Factors ID'd to Predict Fatty Liver in Obese ...

African-American obese teens more susceptible to fatty liver effects on glucose metabolism

Patients Prefer Doctors Who Engage in Face-to-Face Visits

Patients Prefer Doctors Who Engage in Face-to-Face Visits

Patients perceive F2F physicians as more compassionate and better communicators

Flexible Sigmoidoscopy Cuts CRC Incidence, Mortality in Men

Flexible Sigmoidoscopy Cuts CRC Incidence, Mortality in Men

Absolute risks for colorectal cancer, CRC death not reduced for screening group vs. controls in women

is free, fast, and customized just for you!

Already a member?

Sign In Now »