Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase

Inactivation of the retinoblastoma gene (RB1) product, pRB, is common in many human cancers. Targeting downstream effectors of pRB that are central to tumorigenesis is a promising strategy to block the growth of tumors harboring loss-of-function RB1 mutations. One such effector is retinoblastoma-binding protein 2 (RBP2, also called JARID1A or KDM5A), which encodes an H3K4 demethylase. Binding of pRB to RBP2 has been linked to the ability of pRB to promote senescence and differentiation. Importantly, genetic ablation of RBP2 is sufficient to phenocopy pRB’s ability to induce these cellular changes in cell culture experiments. Moreover, germline Rbp2 deletion significantly impedes tumorigenesis in Rb1+/− mice. The value of RBP2 as a therapeutic target in cancer, however, hinges on whether loss of RBP2 could block the growth of established tumors as opposed to simply delaying their onset. Here we show that conditional, systemic ablation of RBP2 in tumor-bearing Rb1+/− mice is sufficient to slow tumor growth and significantly extend survival without causing obvious toxicity to the host. These findings show that established Rb1-null tumors require RBP2 for growth and further credential RBP2 as a therapeutic target in human cancers driven by RB1 inactivation.

Explaining urokinase type plasminogen activator inhibition by amino-5-hydroxybenzimidazole and two naphthamidine-based compounds through quantum biochemistry

Urokinase plasminogen activator (uPA) is a biomarker and therapeutic target for several cancer types whose inhibition has been shown to slow tumor growth and metastasis.

Long-Term Efficacy of S-1 Chemotherapy plus Administration of Octreotide for a Patient with Metastatic Neuroendocrine Tumor (Gastrinoma)

Metastatic neuroendocrine tumors (gastrinomas) have a poor prognosis. Octreotide can reduce gastrin levels and alleviate hormonal symptoms, and possibly slow tumor growth as well. No drugs were available except streptozocin for the treatment of metastatic pancreatic neuroendocrine tumor (PNET) in 2008. We report a case of PNET in a 53-year-old woman with multiple liver tumors treated with S-1 plus octreotide. After 6 months from the initiation of the treatment, the pancreatic tumor and liver metastases regressed, and the patient achieved partial response without the development of any serious adverse event. For more than 8 years, the patient has remained asymptomatic without disease progression and is continuing treatment with octreotide and S-1. A marked suppression of gastrin levels has also been achieved. Combination therapy with octreotide and S-1 has been effective and well tolerated in patients with metastatic gastrinoma.