Lenvatinib is an emerging multi-kinase inhibitor with a preferential anti-angiogenic activity, which has shown efficacy in the treatment of renal cell carcinoma, differentiated thyroid cancer and hepatocellular carcinoma. It inhibits vascular endothelial growth factor receptor family (VEGFR1–3), fibroblast growth factor receptor family (FGFR1–4), platelet-derived growth factor receptor–alpha (PDGFRα), tyrosine-kinase receptor (KIT) and rearranged during transfection receptor (RET). In this review we have evaluated the development from bench to bedside of lenvatinib. PubMed, MEDLINE and clinicaltrials.gov are the sources of data. Furthermore, the preclinical in vitro and in vivo data, as well as efficacy and toxicity results of lenvatinib in the clinic, are presented and discussed. Treatment with lenvatinib causes side effects (hypertension, proteinuria, fatigue and diarrhea), which are predominantly related to the inhibition of angiogenesis. For these reasons, the identification of biomarkers of efficacy and resistance to lenvatinib is a key challenge in order to select responsive patients. This review provides an overview on lenvatinib’s clinical use, perspectives and indications for future development.

A novel class of drugs, antibody-drug conjugates (ADCs), are now rapidly emerging as highly effective treatments for solid tumours. ADCs conjugate conventional chemotherapeutics with highly selective targeted monoclonal antibodies. Anti-HER2 therapies selectively target cancer cells expressing human epidermal growth factor receptor 2 (HER2), among them trastuzumab has been the first HER2-targeting monoclonal antibody to achieve successful results that made it the backbone of anti-HER2 therapies. Trastuzumab drug conjugates (T-DCs), use trastuzumab as a selective antibody to lead cytotoxic drugs inside cancer cells. Trastuzumab-emtansine (T-DM1) and trastuzumab-deruxtecan (T-Dxd) are the two approved T-DCs. T-Dxd along with other five T-DCs represents "second generation ADCs" that has been firstly tested in HER2 positive breast cancer (BC) and then in HER2-low BC and other cancers showing promising results thanks to extraordinary and innovative pharmacokinetic and pharmacodynamic characteristics. The evidence generated so far are establishing them as a completely new class of agents effective in solid cancer treatments but also warrants physicians against unconventional toxicity profiles. The role of T-DCs in HER2-positive BC has been largely reviewed, while in this review, we provided for the first time in literature an overview of trastuzumab drug conjugates (T-DCs) approved and/or in clinical development with a specific focus on their efficacy and safety profile in HER2-low BC and other solid tumours different from BC. We started by analysing T-DCs biological characteristics that underly the differences in T-DCs pharmacodynamics and safety profile, then presented the main evidence on the activity and efficacy of these emerging T-DCs in HER2-low BC and other HER2 overexpressing and/or mutated solid tumours and lastly, we provided an overview of the complex and still evolving scenario in which these compounds should be allocated. A specific focus on possible combination strategies with other drugs such as immunotherapy, chemotherapy and target therapy, to increase T-DCs activity and eventually overcome future upcoming resistance mechanisms, are here also critically reviewed.

Electrochemotherapy is a local non-thermal treatment for cancer ablation. Currently, many studies and case report have investigated the differences in effectiveness of electrochemotherapy with respect to tumor type, chemotherapeutic drug, and route of drug administration. ESOPE trial validated standard operating procedures [SOP] for ECT using the Cliniporator device and demonstrated that ECT is a simple, highly efficacious, and cost-effective treatment of cutaneous and subcutaneous nodules from different primary tumors for cutaneous or superficial lesions. This review has the purpose to summarize current knowledge about clinical effectiveness of electrochemotherapy and future prospects regarding its use on pancreatic cancer and liver metastasis not only.

MBC is a rare disease accounting for almost 1% of all cancers in men and less than 1% of breast cancer. Emerging data on the genetic drivers of predisposition for MBC are available and different risk factors have been associated with its pathogenesis. Genetic alterations, such as pathogenetic variants in BRCA1/2 and other moderate-/low-penetrance genes, along with non-genetic risk factors, have been recognized as pathogenic factors for MBC. Preventive and therapeutic implications could be related to the detection of alterations in predisposing genes, especially BRCA1/2, and to the identification of oncogenic drivers different from FBC. However, approved treatments for MBC remain the same as FBC. Cancer genetic counseling has to be considered in the diagnostic work-up of MBC with or without positive oncological family history. Here, we review the literature, reporting recent data about this malignancy with a specific focus on epidemiology, and genetic and non-genetic risk factors. We introduce the perspective of cancer genetic counseling for MBC patients and their healthy at-risk family members, with a focus on different hereditary cancer syndromes.

The detection of germline pathogenic variants (gPVs) in BRCA1/2 and other breast cancer (BC) genes is rising exponentially thanks to the advent of multi-gene panel testing. This promising technology, coupled with the availability of specific therapies for BC BRCA-related, has increased the number of patients eligible for genetic testing. Implementing multi-gene panel testing for hereditary BC screening holds promise to maximise benefits for patients at hereditary risk of BC. These benefits range from prevention programs to antineoplastic-targeted therapies. However, the clinical management of these patients is complex and requires guidelines based on recent evidence. Furthermore, applying multi-gene panel testing into clinical practice increases the detection of variants of uncertain significance (VUSs). This augments the complexity of patients' clinical management, becoming an unmet need for medical oncologists. This review aims to collect updated evidence on the most common BC-related genes besides BRCA1/2, from their biological role in BC development to their potential impact in tailoring prevention and treatment strategies.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies, mainly originating from hormone-secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout the multiple endocrine neoplasia type 1 (MEN-1) gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signalling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the role and the potential therapeutic implications of gene mutations and NOTCH signalling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential role across all NEN subtypes is required.