Outcomes following long-term disease control with immune checkpoint inhibitors in patients with advanced melanoma.

Immune checkpoint inhibitors (ICI) can achieve durable responses in patients with advanced melanoma, and results from clinical trials suggest cure may be possible for a subset of patients. Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. This study aimed to explore the disease outcomes and survival in a cohort of patients with long-term responses to ICI.

Metastatic Melanoma Treatment in Special Populations.

This review outlines the most up-to-date metastatic melanoma treatment recommendations and relevant risks for patients with solid organ transplants, patients with renal dysfunction, and patients with preexisting autoimmune conditions. These specific treatment populations were excluded from the original clinical trials, which studied immune checkpoint inhibitors and BRAF/MEK inhibitors in the advanced melanoma setting. We have synthesized the current body of literature, mainly case series and retrospective analyses, to reflect the evidence for the treatment of these special patient populations at present.

Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy.

Importance: Acral (AM) and mucosal melanomas (MM) are rare subtypes with a poor prognosis. In those with advanced disease, anti-PD-1 (PD1) therapy has reduced activity compared to that seen in non-acral cutaneous melanoma.

Objective: To determine the efficacy of adjuvant PD1 in resected AM or MM.

Upstream open reading frames control PLK4 translation and centriole duplication in primordial germ cells.

Centrosomes are microtubule-organizing centers comprised of a pair of centrioles and the surrounding pericentriolar material. Abnormalities in centriole number are associated with cell division errors and can contribute to diseases such as cancer. Centriole duplication is limited to once per cell cycle and is controlled by the dosage-sensitive Polo-like kinase 4 (PLK4).

Centrosome defects cause microcephaly by activating the 53BP1-USP28-TP53 mitotic surveillance pathway.

Mutations in centrosome genes deplete neural progenitor cells (NPCs) during brain development, causing microcephaly. While NPC attrition is linked to TP53-mediated cell death in several microcephaly models, how TP53 is activated remains unclear. In cultured cells, mitotic delays resulting from centrosome loss prevent the growth of unfit daughter cells by activating a pathway involving 53BP1, USP28, and TP53, termed the mitotic surveillance pathway.