Romi Gupta

Title : Co- Targeting of specific epigenetic regulators in combination with CDC7 potently inhibit melanoma growth

Abstract:

Melanoma is a highly aggressive skin cancer that frequently metastasizes, but current therapies only benefit some patients. Here, we demonstrate that the serine/threonine kinase cell division cycle 7 (CDC7) is overexpressed in melanoma, and patients with higher expression have shorter survival. Transcription factor ELK1 regulates CDC7 expression, and CDC7 inhibition promotes cell cycle arrest, senescence, and apoptosis, leading to inhibition of melanoma tumor growth and metastasis. Our chemical genetics screen with epigenetic inhibitors revealed stronger melanoma tumor growth inhibition when XL413 is combined with the EZH2 inhibitor GSK343 or BRPF1/2/3 inhibitor OF1. Mechanistically, XL413 with GSK343 or OF1 synergistically altered the expression of tumor-suppressive genes, leading to higher apoptosis than the single agent alone. Collectively, these results identify CDC7 as a driver of melanoma tumor growth and metastasis that can be targeted alone or in combination with EZH2 or BRPF1/2/3 inhibitors.

Audience Take Away:

• Melanoma Treatment remains a challenge because of development of drug resistance, which allows disease to metastasize. Identification and targeting of CDC7 alone or in combination with EZH2 or BRPF1/2/3 inhibitors can be employed as a new therapeutic intervention for melanoma patients.
• New epigenetic regulator along with kinase is involved in melanoma growth and progression.        

Biography:

Dr. Gupta did her BS and MS in India. She then joined Prof. Knud Nierhaus group at Max Planck Institute for Molecular Genetics, Berlin, Germany for her PhD and obtained her degree in the area of ribosome biology and protein translation. After that she worked at Yale University as postdoc where she extensively performed studies to identify new regulator in cancer growth and progression. Many of her studies are published in journals like eLife, PNAS, Cell Reports, Oncogene etc. Currently she is an Assistant Professor in the UAB and Associate scientist at O'Neal Comprehensive Cancer Center at UAB. Her lab Our works on identifying new molecules and pathways and studying their role in tumor initiation and progression. Her long-term goal is to not only identify new molecules and signaling pathways that regulate the disease but also develop more effective and durable cancer therapies.