The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints

Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt prop…

HIF-1a induces downregulated expression of Aurora A in breast cancer cell lines

Background: Aurora A (AURKA) is an oncogenic serine/treonine kinase that play a critical role during mitosis, governing the correct distribution of genetic material to the daughter cells. AURKA is overexpressed in many types of human tumors including breast cancer and its deregulated expression, inducing alteration of mitotic spindle, chromosomal segregation and aneuploidy can lead to malignant transformation of cells. Aims: Since hypoxia is a typical tumoral condition which influences the expression of various proteins involved in proliferation and cell cycle progression, aim of our study was to obtain new insights into AURKA regulation in breast cancer cell lines cultured under normoxic a…

Downregulated expression of Cdc25A gene in MCF-7 breast cancer cell

BRCA1 and BRCA2 variants of uncertain clinical significance and their implications for genetic counseling

sj-pdf-1-tam-10.1177_1758835920975326 – Supplemental material for BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

Supplemental material, sj-pdf-1-tam-10.1177_1758835920975326 for BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients by Lorena Incorvaia, Daniele Fanale, Marco Bono, Valentina Calò, Alessia Fiorino, Chiara Brando, Lidia Rita Corsini, Sofia Cutaia, Daniela Cancelliere, Alessia Pivetti, Clarissa Filorizzo, Maria La Mantia, Nadia Barraco, Stefania Cusenza, Giuseppe Badalamenti, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

BRCA1 and BRCA2 germline mutations in sicilian breast and/or ovarian cancer families and their association with familial profiles

EGF Induces STAT3-Dependent VEGF Expression in HT-29 colon cancer cells

79 VUS VARIANTS IN BRCA GENES OF HEREDITARY BREAST/OVARIAN CANCER

1543P Gemcitabine in classic Kaposi’s sarcoma: A pilot study

502P Impact of different selection approaches for identifying Lynch syndrome-related colorectal cancer patients

Genetic and Molecular Characterization of The Human Osteosarcoma 3AB-OS Cancer Stem Cell Line: A Possible Model For Studying Osteosarcoma Origin and Stemness

Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype wit…

Prognostic Role of Plasma PD-1, PD-L1, pan-BTN3As and BTN3A1 in Patients Affected by Metastatic Gastrointestinal Stromal Tumors: Can Immune Checkpoints Act as a Sentinel for Short-Term Survival?

Gastrointestinal stromal tumors (GISTs) represent 1% of all primary gastrointestinal tumors. Immune surveillance is often overcome by cancer cells due to the activation of immunoregulatory molecules such as programmed death protein (PD-1) and its ligand PD-L1, and butyrophilin sub-family 3A/CD277 receptors (BTN3A). Because several studies demonstrated that tumor PD-1 and PD-L1 expression may have a prominent prognostic function, this investigation aimed to discover if soluble forms of these molecules may be useful in predicting survival of metastatic GIST (mGIST) patients. Through specific ad hoc developed ELISA assays not yet available on the market, the circulating PD-1, PD-L1, BTN3A1, an…

Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer

In the last decade, tumor-infiltrating lymphocytes (TILs) have been recognized as clinically relevant prognostic markers for improved survival, providing the immunological basis for the development of new therapeutic strategies and showing a significant prognostic and predictive role in several malignancies, including ovarian cancer (OC). In fact, many OCs show TILs whose typology and degree of infiltration have been shown to be strongly correlated with prognosis and survival. The OC histological subtype with the higher presence of TILs is the high-grade serous carcinoma (HGSC) followed by the endometrioid subtype, whereas mucinous and clear cell OCs seem to contain a lower percentage of TI…

Finding the right biomarker for renal cell carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response

Abstract Background The variability of clinical response to immune checkpoint inhibitors in RCC patients makes necessary the discovery of predictive biomarkers for patient selection. Emerging evidence has revealed a multitude of silenced genes and deregulated signalling pathways. These findings point towards extensive microRNAs (miRNAs) regulation and imply epigenetic reprogramming as a key feature of RCC. The aim of this study was to analyze the peripheral lymphocyte miRNA expression profile in metastatic RCC patients undergoing nivolumab treatment, to identify a lymphocyte miRNA signature specifically expressed in patients with partial or complete response (RP; RC) >12 months. Methods miR…

MUTYH-associated tumor syndrome: The other face of MAP

MUTYH gene is involved in the base excision repair (BER) mechanism and its pathogenic alterations are associated with colorectal polyposis and cancer. MUTYH-associated polyposis (MAP) is a condition which is inherited in an autosomal recessive manner. MAP patients, beyond colorectal cancer (CRC), may develop other types of tumors, including duodenal, breast, ovarian, pancreatic, bladder and skin cancers. Carriers of biallelic MUTYH likely pathogenic/pathogenic variants exhibit a high lifetime risk of CRC, though cancer risk evidence becomes less clear when monoallelic carriers and extraintestinal tumors are considered. However, several studies recently reported an increased genetic suscepti…

Analysis of Germline Gene Copy Number Variants of Patients with Sporadic Pancreatic Adenocarcinoma Reveals Specific Variations

<b><i>Objectives:</i></b> The rapid fatality of pancreatic cancer is, in large part, the result of diagnosis at an advanced stage in the majority of patients. Identification of individuals at risk of developing pancreatic adenocarcinoma would be useful to improve the prognosis of this disease. There is presently no biological or genetic indicator allowing the detection of patients at risk. Our main goal was to identify copy number variants (CNVs) common to all patients with sporadic pancreatic cancer. <b><i>Methods:</i></b> We analyzed gene CNVs in leukocyte DNA from 31 patients with sporadic pancreatic adenocarcinoma and from 93 matched contr…

POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes

POLE, POLD1, and NTHL1 are involved in DNA replication and have recently been recognized as hereditary cancer-predisposing genes, because their alterations are associated with colorectal cancer and other tumors. POLE/POLD1-associated syndrome shows an autosomal dominant inheritance, whereas NTHL1-associated syndrome follows an autosomal recessive pattern. Although the prevalence of germline monoallelic POLE/POLD1 and biallelic NTHL1 pathogenic variants is low, they determine different phenotypes with a broad tumor spectrum overlapping that of other hereditary conditions like Lynch Syndrome or Familial Adenomatous Polyposis. Endometrial and breast cancers, and probably ovarian and brain tumo…

Can the tumor-agnostic evaluation of MSI/MMR status be the common denominator for the immunotherapy treatment of patients with several solid tumors?

Alterations in short-repetitive DNA sequences, known as microsatellite instability (MSI), can reflect deficiencies in Mismatch Repair (MMR) system which represents a major player in DNA integrity maintenance. The incidence of MSI-H/dMMR has been shown to be variable depending on the tumor type. Several studies confirmed that dMMR/MSI status, although less frequent than PD-L1 expression, may better predict response to immune-checkpoint inhibitors (ICIs) in patients with solid tumors. In October 2016, the FDA granted pembrolizumab as breakthrough therapy for the treatment of non-CRC, MSI-H/dMMR tumors, providing, for the first time, a tumor-agnostic indication. In the next future, the tissue-…

Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?

An important molecular target for metastatic CRC treatment is the epidermal growth factor receptor (EGFR). Many potential biomarkers predictive of response to anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have been retrospectively evaluated, including EGFR activation markers and EGFR ligands activation markers. With regard to the "negative predictive factors" responsible for primary or intrinsic resistance to anti-EGFR antibodies a lot of data are now available. Among these, KRAS mutations have emerged as a major predictor of resistance to panitumumab or cetuximab in the clinical setting and several studies of patients receiving first and subsequent lines of treatment have sho…

Challenges and advances for the treatment of renal cancer patients with brain metastases: From immunological background to upcoming clinical evidence on immune-checkpoint inhibitors

The introduction of checkpoint inhibitors (ICIs) in renal cell carcinoma (RCC) treatment landscape, resulted in improvements in overall survival (OS) in metastatic patients. Brain metastases (BMs) are a specific metastatic site of interest representing a predictive factor of poor prognosis. Patients with BMs were usually excluded from prospective clinical trials in the past. Despite recent evidence suggest the efficacy and safety of ICIs, the BMs treatment remains a challenge; the immunotherapy responsiveness seems to be multifactorial and dependent on several factors, such as the genetic intratumor heterogeneity and the immunosuppressive role of the brain tumor microenvironment. This revie…

1535P Exploring the dynamic crosstalk between immune system and genetics in a cohort of 116 completely resected gastrointestinal stromal tumors (GISTs)

Gene signatures in CRC and liver metastasis

Colorectal cancer (CRC) is one of the most common causes of cancer-related death with a worldwide incidence of almost a million cases annually in both males and females. The accelerated decrease in CRC incidence rates from 1998 to 2006 largely reflects the advances in diagnosis and treatment that have enabled to detect and remove precancerous polyps. However, the screening technology has not resulted in major improvements in the prognosis of patients with advanced cancer and the liver metastasis remains the major cause of death in CRC. About 25% of patients have detectable liver metastasis at diagnosis, that are classified as “synchronous” lesions and approximately 70% of patients develop a…

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase ( KIT) exon 11 PV were included in the study. We analyzed the t…

Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.

The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor γ (PPARγ) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in b…

Breast cancer genome-wide association studies: there is strength in numbers.

Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-spe…

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

Background Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. Patients and methods Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relativ…

the proximal leptin gene promoter is regulated by ppar gamma agonist in MCF-7 and MDA-MB-231 breast cancer cells

VUS variants in BRCA genes of hereditary breast/ovarian cancer

Central Nervous System Malignancies

The primitive neoplasms of the central nervous system (CNS) are a rare and heterogeneous group of malignancies. Brain metastases (BMs) are the most frequent intracranial tumor, and their incidence is rising in the last few decades. Primary tumors more often complicated by BMs are lung cancer, breast cancer, and melanoma. Neuroimaging techniques, mainly magnetic resonance imaging (MRI), play a key role for the diagnosis of BMs. The management of BMs is based on a multimodal approach, including symptomatic treatment, local treatment, such as surgery, stereotactic radiosurgery (SRS), and whole brain radiotherapy (WBRT), and systemic therapy, such as chemotherapy, target therapy, or immunothera…

sj-pdf-1-tam-10.1177_1758835920975326 – Supplemental material for BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

Supplemental material, sj-pdf-1-tam-10.1177_1758835920975326 for BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients by Lorena Incorvaia, Daniele Fanale, Marco Bono, Valentina Calò, Alessia Fiorino, Chiara Brando, Lidia Rita Corsini, Sofia Cutaia, Daniela Cancelliere, Alessia Pivetti, Clarissa Filorizzo, Maria La Mantia, Nadia Barraco, Stefania Cusenza, Giuseppe Badalamenti, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

166P Hereditary breast, ovarian and pancreatic cancers: Looking beyond the BRCA1/2 genes

Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2

Simple Summary Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative for BRCA1 or BRCA2 pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result for BRCA1/2 pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, PTEN, TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform…

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and a…

Potential miRNAs involved in molecular pathways mediating the anticancer effects of short term starvation in breast cancer cells treated with doxorubicin

Background: In recent years, increasing evidences showed that several types of dietary approaches restricting food intake, including Short Term Starvation (STS), may exert a protective role against aging and other age-related pathologies as well as cancer. Interestingly, the dietary restriction showed significant anticancer effects able to prevent cancer onset, slow its progression and improve therapy response. Since recent studies showed that miRNAs may modulate sensibility/resistance to antiblastic therapy, the aim of our study was to investigate the STS-induced molecular changes in breast cancer cells treated with doxorubicin, focusing our attention on miRNA expression profile. Materials…

247P Population-based testing for hereditary breast and ovarian cancer in a cohort of 1,346 patients from Southern Italy (Sicily): When historical background affects genetics

The role of microRNAs in cancer: diagnostic and prognostic biomarkers and targets of therapies

Introduction: miRNAs are noncoding RNAs that target specific mRNA with subsequent regulation of particular genes, implicated in various biological processes. In cancer, miRNAs could show a different expression from normal tissues. miRNAs have a role as oncogenes when they target tumor suppressor genes and similarly they are tumor suppressors when they target oncogenes. Areas covered: In this review, areas covered include the role of miRNAs in cancer diagnosis, prognosis and research for achievement of therapeutic strategies implicating miRNAs in oncology. As biogenesis of miRNAs is fundamental to understand their usefulness, this has also been discussed. Both miRNA expression profiles in ca…

Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC).

Recently, immunotherapy has been shown to be an effective and helpful therapeutic option for the treatment of advanced non-small-cell lung cancer (NSCLC). The activity of antitumor T cells may be restored through the checkpoint blockade using anti-programmed death 1 or anti-programmed death ligand 1 (PD-L1) antibodies, showing, in several cancer patients, an increased progression-free survival and overall survival compared with classical chemotherapy. As recently shown by several studies, the PD-L1 expression levels in tumors may offer a selection criterion for patients to predict their immunotherapy response. In particular, NSCLC patients with high tumor PD-L1 levels (proportional score ≥ …

33 EFFECT OF miR-21, miR-182 AND let-7i ON TSP-1 EXPRESSION IN COLON CANCER CELL LINE

A novel predictive biomarker of immunotherapy response in metastatic renal cell carcinoma (mRCC): The lymphocyte microRNA expression profile.

e16109 Background: Predicting which patient with metastatic renal cell carcinoma (mRCC) will benefit from immune checkpoints inhibitors (ICPIs) still remain an issue. Biological factors particular to certain individuals have a clear effect on variation in response. Emerging evidence suggests that small non-coding RNA, such as microRNAs (miRNAs), are critical modulators of numerous cellular processes, including immune surveillance. The main aim of this study was to analyze the lymphocyte miRNA expression profile in mRCC patients and dynamic changes after the treatment with ICPI, in order to investigate the molecular mechanisms and signaling pathways involved in ICPI response and their poten…

HIF-1 is involved in the negative regulation of AURKA expression in breast cancer cell lines under hypoxic conditions

Numerous microarray-based gene expression studies performed on several types of solid tumors revealed significant changes in key genes involved in progression and regulation of the cell cycle, including AURKA that is known to be overexpressed in many types of human malignancies. Tumor hypoxia is associated with poor prognosis in several cancer types, including breast cancer (BC). Since hypoxia is a condition that influences the expression of many genes involved in tumorigenesis, proliferation, and cell cycle regulation, we performed a microarray-based gene expression analysis in order to identify differentially expressed genes in BC cell lines exposed to hypoxia. This analysis showed that h…

738P Soluble PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTN2A1 as predictive biomarkers of nivolumab response in patients with metastatic clear cell renal carcinoma

MicroRNAs in colorectal cancer stem cells: new regulators of cancer stemness?

Recently, the hypothesis that colorectal tumors originate from a subpopulation of cells called ‘cancer stem cells' (CSCs) or tumor-initiating cells, which exhibit stem-like features, has been confirmed experimentally in various human cancers. Several studies have confirmed the existence of colorectal CSCs (CRCSCs) and have demonstrated that this rare cell population can be isolated by the expression of specific cell surface biomarkers. MicroRNAs (miRNAs) are a class of small non-coding RNAs, which are crucial for post-transcriptional regulation of gene expression and participate in a wide variety of biological functions, including development, cell proliferation, differentiation, metabolism…

Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?

e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasm…

BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

Background: Several available data suggest the association between specific molecular subtypes and BRCA1/2 mutational status. Previous investigations showed the association between BRCA1/2 pathogenic variants (PVs) in specific genomic regions and phenotypic variations of cancer relative risk, while the role of PV type and location in determining the breast cancer (BC) phenotypic features remains still unclear. The aim of this research was to describe the germline BRCA1/2 PVs in triple-negative breast cancer (TNBC) versus luminal-like BC and their potential leverage on BC phenotype. Patients & methods: We retrospectively collected and analyzed all clinical information of 531 patients wit…

Monoclonal antibodies for the treatment of non-hematological tumors: a safety review

Introduction: The introduction of monoclonal antibodies (moAbs) into clinical practice revolutionized the treatment strategies in several solid tumors. These agents differ from cytotoxic chemotherapy for their mechanism of action and toxicity. By targeting specific antigens present on healthy cells and modulating immune system activity, these biological drugs are able to generate a wide spectrum of peculiar adverse events that can negatively impact on patients' quality of life. Areas covered: In this review, the main side effects associated with the use of moAbs have been described to show their incidence and current management strategies, which may drive clinicians in their daily practice.…

Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome

About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlini…

Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells

Zoledronic acid (ZOL) is the most potent nitrogen-containing bisphosphonate (N-BPs) that strongly binds to bone mineral and acts as a powerful inhibitor of bone resorption, already clinically available for the treatment of patients with osteolytic metastases. Recent data also suggest that ZOL, used in breast cancer, may provide more than just supportive care modifying the course of the disease, though the possible molecular mechanism of action is still unclear. As breast cancer is one of the primary tumours with high propensity to metastasize to the bone, we investigated, for the first time, differential gene expression profile on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells tre…

Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non–Small-Cell Lung Cancer (NSCLC)

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