Basal cell carcinoma (BCC) is one of the most common neoplasms in the population. A good prognosis and mainly non-aggressive development have made it underdiagnosed and excluded from the statistics. Due to the availability of efficient surgical therapy, BCC is sometimes overlooked in the search for novel therapies. Most clinicians are unaware of its complicated pathogenesis or the availability of effective targeted therapy based on Hedgehog inhibitors (HHI) used in advanced or metastatic cases. Nevertheless, the concomitance and esthetic burden of this neoplasm are severe. As with other cancers, its pathogenesis is multifactorial and complicated with a network of dependencies. Although the tumour microenvironment (TME), genetic aberrations, and risk factors seem crucial in all skin cancers, in BCC they all have become accessible as therapeutic or prevention targets. The results of this review indicate that a central role in the development of BCC is played by the Hedgehog (Hh) signalling pathway. Two signalling molecules have been identified as the main culprits, namely Patched homologue 1 (PTCH1) and, less often, Smoothened homologue (SMO). Considering effective immunotherapy for other neoplastic growths being introduced, implementing immunotherapy in advanced BCC is pivotal and beneficial. Up to now, the US Food and Drug Administration (FDA) has approved two inhibitors of SMO for the treatment of advanced BCC. Sonidegib and vismodegib are registered based on their efficacy in clinical trials. However, despite this success, limitations might occur during the therapy, as some patients show resistance to these molecules. This review aims to summarize novel options of targeted therapies in BCC and debate the mechanisms and clinical implications of tumor resistance.

Cholangiocarcinomas (CCAs) are rare but aggressive tumours with poor diagnosis and limited treatment options. Molecular targeted therapies became a promising proposal for patients after progression under first-line chemical treatment. In light of an escalating prevalence of CCA, it is crucial to fully comprehend its pathophysiology, aetiology, and possible targets in therapy. Such knowledge would play a pivotal role in searching for new therapeutic approaches concerning diseases’ symptoms and their underlying causes. Growing evidence showed that fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) pathway dysregulation is involved in a variety of processes during embryonic development and homeostasis as well as tumorigenesis. CCA is known for its close correlation with the FGF/FGFR pathway and targeting this axis has been proposed in treatment guidelines. Bearing in mind the significance of molecular targeted therapies in different neoplasms, it seems most reasonable to move towards intensive research and testing on these in the case of CCA. However, there is still a need for more data covering this topic. Although positive results of many pre-clinical and clinical studies are discussed in this review, many difficulties lie ahead. Furthermore, this review presents up-to-date literature regarding the outcomes of the latest clinical data and discussion over future directions of FGFR-directed therapies in patients with CCA.

The ratio of positive lymph nodes (LNs) to the total LN harvest is called the LN ratio (LNR). It is an independent prognostic factor in gastric cancer (GC). The aim of the current study was to evaluate the impact of neoadjuvant chemotherapy (NAC) on the LNR (ypLNR) in patients with advanced GC. We retrospectively analyzed the data of patients with advanced GC, who underwent gastrectomy with N1 and N2 (D2) lymphadenectomy between August 2011 and January 2019 in the Department of Surgical Oncology at the Medical University of Lublin. The exclusion criteria were a lack of preoperative NAC administration, suboptimal lymphadenectomy (<D2 and/or removal of less than 15 lymph nodes), and a lack of data on tumor regression grading (TRG) in the final pathological report. A total of 95 patients were eligible for the analysis. A positive correlation was found between the ypLNR and tumor diameter (p < 0.001), post treatment pathological Tumour (ypT) stage (p < 0.001), Laurén histological subtype (p = 0.0001), and the response to NAC (p < 0.0001). A multivariate analysis demonstrated that the ypLNR was an independent prognostic factor in patients with intestinal type GC (p = 0.0465) and in patients with no response to NAC (p = 0.0483). In the resection specimen, tumor diameter and depth of infiltration, Laurén histological subtype, and TRG may reflect the impact of NAC on LN status, as quantified by ypLNR in advanced GC.

The prognostic value of the systemic inflammatory response markers, namely neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) has not yet been clarified in patients undergoing neoadjuvant chemotherapy (NAC) and gastrectomy for advanced gastric cancer (GC) in the Eastern European population. This study aimed to verify the prognostic value of NLR, PLR, and LMR in GC patients undergoing multimodal treatment. One hundred six GC patients undergoing NAC and gastrectomy between 2012 and 2020 were included. Analysed blood samples were obtained prior to NAC (pre-NAC group) and before surgical treatment (post-NAC group). To evaluate the prognostic value of the NLR, LMR, and PLR, univariable and multivariable overall survival (OS) analyses were performed. In the pre-NAC group, elevated NLR and PLR were associated with significantly higher risk of death (mOS: 36 vs. 87 months; HR = 2.21; p = 0.0255 and mOS: 30 vs. 87 months; HR = 2.89; p = 0.0034, respectively). Additionally, a significantly higher risk of death was observed in patients with elevated NLR in the post-NAC group (mOS: 35 vs. 87 months; HR = 1.94; p = 0.0368). Selected systemic inflammatory response markers (NLR, PLR) are significant prognostic factors in patients with advanced GC treated with NAC and gastrectomy, as shown in the Eastern European population.

Peritoneal metastases (PM) of gastric cancer (GC) are characterized by a particularly poor prognosis, with median survival time of 6 months, and virtually no 5-year survival reported. Conversion therapy for GC is defined as a surgical treatment aiming at an R0 resection after systemic chemotherapy for tumours that were originally unresectable (or marginally resectable) for technical and/or oncological reasons. The aim of the present study was to evaluate early and late outcomes in GC patients with PM who underwent the cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant (conversion) chemotherapy. Thirty patients with stage IV GC underwent CRS plus HIPEC. Severe grade III/IV (Clavien-Dindo classification) complications occurred in 13 (43%) patients. The Comprehensive Complication Index (CCI) ranged from 8.7 to 100 (median, 42.4). In the multivariate survival analysis, ypT2 and P3 (according to the Japanese classification of the PM severity) were favourable and adverse prognostic factors p = 0.031 and o = 0.035, respectively. Estimated 1- and 3-year survival was 73.9% and 36.6%, respectively. The median survival was 19.3 months. Conclusion: Conversion surgery, including extended gastrectomy and multi-organ resections followed by HIPEC performed after systemic chemotherapy therapy for GC with PM is justified in downstaged patients with ypT2 and limited (less than P3) PM.