Progress and Challenges of Messenger RNA Vaccines in the Therapeutics of NSCLC.

The introduction of immune checkpoint inhibitors in the therapeutics of non-small cell lung cancer (NSCLC) has been a game-changer in the management of patients with lung cancer; however, challenges do exist since a non-negligible subset of patients does not respond to therapy. Various immunotherapeutic anticancer strategies have been increasingly developed in recent years, including monoclonal antibodies, adoptive T-cell therapy, and vaccines. Fueled by their rapid drug development and successful implementation during the COVID-19 pandemic, messenger RNA (mRNA) vaccines represent an emerging therapeutic approach in other fields of medicine, including oncology. Several clinical trials are currently being conducted to assess the safety and efficacy of mRNA vaccines regarding a variety of solid tumors. Combining mRNA vaccines with other immunotherapeutic approaches has also been suggested and is currently under investigation. Although, in the case of NSCLC, the investigation is still in its early stages, the initial results raise the need for clinician awareness of these promising therapies. To this end, in the present review, we aim to summarize current advances in the development of mRNA vaccines in NSCLC therapeutics and discuss pragmatic challenges regarding their drug development and the different opportunities for implementation.

Estrogen-Receptor-Low-Positive Breast Cancer: Pathological and Clinical Perspectives.

The expression of estrogen receptors (ERs) in breast cancer (BC) represents a strong prognostic and predictive biomarker and directs therapeutic decisions in early and advanced stages. ER-low-positive BC, defined by the immunohistochemical (IHC) expression of ERs from 1% to 9%, constitutes a distinct subset of total BC cases. Guidelines recommend that a low expression of ERs be reported in pathology reports since the benefit of endocrine therapy in patients with ER-low-positive BC is uncertain. Recently, several cohorts, mostly of a retrospective nature, have been published, reporting the clinicopathological characteristics and outcomes of ER-low-positive BC. However, the majority of the data focus on early-stage BC and the use of (neo)adjuvant therapy, and there is a significant lack of data regarding metastatic ER-low-positive BC. Further factors, including tumor heterogeneity as well as the potential loss of ER expression due to endocrine resistance, should be considered. Including patients with ER-low-positive BC in clinical trials for triple-negative breast cancer (TNBC) might improve the understanding of this entity and allow novel therapeutic approaches. The design and conduction of randomized clinical trials regarding this subgroup of patients are greatly anticipated.