New therapeutic approaches that antagonize tumour-promoting phenotypes in lung cancer are needed to improve patient outcomes. Chromosomal instability (CIN) is a hallmark of lung cancer characterized by the ongoing acquisition of genetic alterations that include the gain and loss of whole chromosomes or segments of chromosomes as well as chromosomal rearrangements during cell division. Although it provides genetic diversity that fuels tumour evolution and enables the acquisition of aggressive phenotypes like immune evasion, metastasis, and drug resistance, too much CIN can be lethal because it creates genetic imbalances that disrupt essential genes and induce severe proteotoxic and metabolic stress. As such, sustaining advantageous levels of CIN that are compatible with survival is a fine balance in cancer cells, and potentiating CIN to levels that exceed a tolerable threshold is a promising treatment strategy for inherently unstable tumours like lung cancer. Kinesins are a superfamily of motor proteins with many members having functions in mitosis that are critical for the correct segregation of chromosomes and, consequently, maintaining genomic integrity. Accordingly, inhibition of such kinesins has been shown to exacerbate CIN. Therefore, inhibiting mitotic kinesins represents a promising strategy for amplifying CIN to lethal levels in vulnerable cancer cells. In this review, we describe the concept of CIN as a therapeutic vulnerability and comprehensively summarize studies reporting the clinical and functional relevance of kinesins in lung cancer, with the goal of outlining how kinesin inhibition, or “targeting kinesins”, holds great potential as an effective strategy for treating lung cancer.

The channel-forming glycoprotein Pannexin 3 (PANX3) functions in cutaneous wound healing and keratinocyte differentiation, but its role in skin homeostasis through aging is not yet understood. We found that PANX3 is absent in newborn skin but becomes upregulated with age. We characterized the skin of global Panx3 knockout mice (KO) and found that KO dorsal skin showed sex-differences at different ages, but generally had reduced dermal and hypodermal areas compared to aged-matched controls. Transcriptomic analysis of KO epidermis revealed reduced E-cadherin stabilization and Wnt signaling compared to WT, consistent with the inability of primary KO keratinocytes to adhere in culture, and diminished epidermal barrier function in KO mice. We also observed increased inflammatory signaling in KO epidermis and higher incidence of dermatitis in aged KO mice compared to wildtype controls. These findings suggest that during skin aging, PANX3 is critical in the maintenance of dorsal skin architecture, keratinocyte cell-cell and cell-matrix adhesion and inflammatory skin responses.