Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001.

Selpercatinib is indicated for locally advanced/metastatic -activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in -activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm).

Case Report: Complete pathologic response to neoadjuvant selpercatinib in a patient with resectable early-stage fusion-positive non-small cell lung cancer.

The LIBRETTO-001 trial demonstrated the activity of the selective rearrangement during transfection (RET) inhibitor selpercatinib in advanced fusion-positive non-small cell lung cancer (NSCLC) and resulted in the drug's approval for this indication. A cohort that included neoadjuvant and adjuvant selpercatinib was opened on LIBRETTO-001 for early-stage fusion-positive NSCLC with the primary endpoint of major pathologic response. A patient with a stage IB (cT2aN0M0) fusion-positive NSCLC received 8 weeks of neoadjuvant selpercatinib at 160 mg twice daily followed by surgery.

Selpercatinib in Patients With Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial.

Purpose: Selpercatinib, a first-in-class, highly selective, and potent CNS-active RET kinase inhibitor, is currently approved for the treatment of patients with fusion-positive non-small-cell lung cancer (NSCLC). We provide a registrational data set update in more than double (n = 316) of the original reported population (n = 144) and better characterization of long-term efficacy and safety.

Methods: Patients were enrolled to LIBRETTO-001, a phase I/II, single-arm, open-label study of selpercatinib in patients with -altered cancers.

Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial.

Background: Selpercatinib is a first-in-class, highly selective RET kinase inhibitor with CNS activity that has shown efficacy in RET fusion-positive lung and thyroid cancers. RET fusions occur rarely in other tumour types. We aimed to investigate the efficacy and safety of selpercatinib in a diverse group of patients with RET fusion-positive non-lung or thyroid advanced solid tumours (ie, a tumour-agnostic population).

Increased estrogen receptor beta expression correlates with decreased spine formation in the rat hippocampus.

Estrogens play an important role in the brain function acting through two receptor types, ERalpha and ERbeta, both well-recognized as transcription factors. In this study, we investigated the ERbeta mRNA and protein levels in the rat hippocampus by using two in vivo models that are known to affect synapse formation. Natural estrous-proestrous cycle was used as a model in which a marked decrease in the density of hippocampal synapses was previously observed between proestrus and estrus.

Non-nuclear estrogen receptor beta and alpha in the hippocampus of male and female rats.

Estrogens play important roles in the brain, acting through two receptor types, ERalpha and ERbeta, both recognized as transcription factors. In this study, we investigated the ERbeta mRNA and protein expression in the male and female rat brain, focusing on the hippocampus, and comparing with well-known ERalpha expression patterns. Extranuclear ERbeta localization, as shown by light microscopic immunocytochemistry and tissue fractionation experiments, was noted in the hippocampus, whereas nuclear ERbeta was present in the amygdala.

Evaluation of mRNA expression of estrogen receptor beta and its isoforms in human normal and neoplastic endometrium.

Endometrial cancer is well known to be estrogen-dependent. Two estrogen receptor types, ERalpha and ERbeta, are major mediators of a diversity of biologic functions of estrogen and play an important role in estrogen-dependent tissues and cancers. Cloning of ERbeta was followed by the discovery of a variety of its isoforms.

[Estrogen receptors in the brain].

Estrogen plays an important role in changes taking place in the brain through the regulation of growth and differentiation of axons and dendrites, influence on plasticity, support of survival as well cognitive and behavioral functions. The classical mode of estrogen action is through the activation of its receptors, transcription factors. Two such estrogen receptors have been cloned, ER alpha i ER beta.

Matrix metalloproteinases in the adult brain physiology: a link between c-Fos, AP-1 and remodeling of neuronal connections?

Matrix metalloproteinases (MMPs), together with their endogenous inhibitors (TIMPs) form an enzymatic system that plays an important role in a variety of physiological and pathological conditions. These proteins are also expressed in the brain, especially under pathological conditions, in which glia as well as invading inflammatory cells provide the major source of the MMP activity. Surprisingly little is known about the MMP function(s) in adult neuronal physiology.