Highlights of This Issue

Microtubule poisons such as paclitaxel are the most commonly utilized first-line chemotherapeutics. However, chemotherapeutic resistance can occur and the mechanistic understanding by which treatment induces survival is limited. Here, mitotic slippage-induced senescence is identified as a route by which the senescence-associated secretory phenotype (SASP) engenders paracrine tumorigenesis in an autophagy-dependent manner. Combined treatment with autophagy inhibitors resulted in senescence bypass and cell death. Importantly, p53 status was found to dictate success to such combinatorial sensitization. Thus, clinical treatment regimens targeting senescence and SASP could provide an effective combinatorial strategy with anti-mitotic drugs.

There is a growing interest in identifying specific tumor cell niches/organs, termed the premetastatic reservoir, where disseminated cancer cells may acquire chemoresistance to remain quiescent for a long-term period. This study demonstrated that the thymus, particularly the atrophied thymus, serves as a premetastatic reservoir for melanoma cells. Chemotherapeutic treatment with doxorubicin initiates activation of p53 in nonmalignant thymic cells: thymic epithelial cells (TECs) and thymocytes, leading to apoptosis in thymocytes and senescence in TECs, cooperatively resulting in a thymic proinflammatory condition. This inflammatory thymic microenvironment, in turn, induces thymus-harboring melanoma cells to acquire chemoresistant features.

Retinoblastoma should not be biopsied for fear of extraocular tumor dissemination; thus, tumor DNA is not used for diagnosis or prognosis. The current study demonstrates that tumor-derived cell-free DNA (cfDNA) is present in aqueous humor, the clear fluid in front of the eye, which can be safely sampled. For the first time, these data demonstrate in vivo access to tumor DNA which can be correlated with genomic alterations and therapeutic tumor response. Importantly, chromosome 6p gain was significantly associated with increased odds of an eye failing treatment and ultimately requiring enucleation. Using aqueous as a liquid biopsy provides new insight into tumorigenesis for this rare cancer.

An adequate blood supply is critical for the development and progression of solid tumors, such as head and neck squamous cell carcinoma (HNSCC). Ludwig and colleagues describe a new mechanism for angiogenesis in HNSCC driven by tumor-derived exosomes (TEX). These exosomes carry a variety of pro-angiogenic proteins and directly interact with endothelial cells, inducing the formation of new blood vessels. In vivo, TEX enhance vascularization of tumor tissues and facilitate cancer progression. These results emphasize the need for a deeper understanding of this novel angiogenic mechanism and of the role TEX plays in HNSCC progression.