Pavlos Msaouel: Should We Always Combine Bevacizumab and Erlotinib in Rare Kidney Cancer?
Pavlos Msaouel, Assistant Professor of Genitourinary Medical Oncology at MD Anderson Cancer Center, shared a post on X:
“Should we always combine bevacizumab (anti‑VEGF) and erlotinib (anti-EGFR) in rare kidney cancer?
We dissected Molecular Cancer Therapeutics their individual roles in Renal Medullary Carcinoma (RMC) and FH‑deficient RCC via tissue profiling, cell line and animal models.
Bulk RNA‑seq of human tissue samples suggested that both tumors upregulate EGFR but not VEGF. In vitro, RMC and FH‑deficient RCC cell lines (but not clear cell RCC) respond to erlotinib treatment.
Therapeutic studies in PDX models suggested that FH-RCC responds to bevacizumab or erlotinib whereas RMC more profoundly responds to erlotinib and is resistant to bevacizumab (consistent with our prior PNAS results in separate models.
Mechanistically, we noted that our RMC model expressed higher total EGFR while the FH-deficient RCC model harbored higher pSRC(Y416, a potential escape node from EGFR blockade).
Take-aways:
Prioritize targeting EGFR and not VEGF for RMC. For FH-deficient RCC can hit both VEGF and EGFR. Subtype‑guided therapy can sharpen outcomes for these rare cancers. These insights directly led to development of contemporary RMC therapies.”
Title: Differential Efficacy of Bevacizumab and Erlotinib in Preclinical Models of Renal Medullary Carcinoma and Fumarate Hydratase-Deficient Renal Cell Carcinoma
Journal: AACR
Authors: Niki M Zacharias, Manuel Ozambela, Menuka Karki, Rong He, Pankaj K Chauhan, Pedro I Pesquera, Andres E Hernandez Gonzalez, Oscar Ochoa, Alberto Pieretti, Huiqin Chen, Carolyn De La Cerda, Zhiyuan Yu, Abha Grover, Samantha Hicks-Peña, Natalie W Fowlkes, Lei Wang, Tapati Maity, Priya Rao, Giannicola Genovese, Nizar M Tannir, Jose A Karam, Pavlos Msaouel
Title: SMARCB1 regulates the hypoxic stress response in sickle cell trait
Journal: PNAS
Authors: Melinda Soeung, Luigi Perelli, Ziheng Chen, Eleonora Dondossola, I-Lin Ho, Federica Carbone, Li Zhang, Hania Khan, Courtney N Le, Cihui Zhu, Michael D Peoples, Ningping Feng, Shan Jiang, Niki Millward Zacharias, Rosalba Minelli, Daniel D Shapiro, Angela K Deem, Sisi Gao, Emily H Cheng, Donatella Lucchetti, Cheryl L Walker, Alessandro Carugo, Virginia Giuliani, Timothy P Heffernan, Andrea Viale, Nizar M Tannir, Giulio F Draetta, Pavlos Msaouel, Giannicola Genovese
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