CAR-T cell therapy for breast cancer: Current status and future perspective.

Within the expanding therapeutic landscape for breast cancer (BC), metastatic breast cancer (MBC) remains virtually incurable and tend to develop resistance to conventional treatments ultimately leading to metastatic progression and death. Cellular immunotherapy (CI), particularly chimeric antigen receptor-engineered T (CAR-T) cells, has emerged as a promising approach for addressing this challenge. In the wake of their striking efficacy against hematological cancers, CAR-T cells have also been used where the clinical need is greatest - in patients with aggressive BCs.

Targeting Autophagy in Breast Cancer.

Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differences in terms of incidence, response to diverse treatments, risk of disease progression, and sites of metastases. In the last years, several molecular targets have emerged and new drugs, targeting PI3K/Akt/mTOR and cyclinD/CDK/pRb pathways and tumor microenvironment have been integrated into clinical practice. However, it is clear now that breast cancer is able to develop resistance to these drugs and the identification of the underlying molecular mechanisms is paramount to drive further drug development.

A potential prognostic marker in primitive lung neuroendocrine tumor: A case report.

Background: The diagnosis and monitoring of primitive lung neuroendocrine tumors (lung pNETs) are usually performed by the measurement of serum chromogranin A (CgA) and urinary 5-hydroxyindolacetic acid (5-HIAA) levels. However, imaging techniques are necessary due to the poor diagnostic efficiency of the laboratory tests.

Methods: A total-body computed tomography and bone scintigraphy scans showed multiple hepatic and bone metastases of a 55-year-old man affected by well-differentiated lung pNETs without severe initial symptoms.

Genetic trajectory and immune microenvironment of lung-specific oligometastatic colorectal cancer.

Genetics and immunologic dynamics pushing the evolution of colorectal cancer (CRC) from the primary tumor to the metastases are largely unknown; cancer heterogeneity makes challenging both therapy and mechanistic studies. We selected patients developing CRC with lung-limited metastatic disease as only illness during their life in order to find any relevant genotype-phenotype relationship. Analysis of 523 cancer-relevant genes and of immune cells infiltration in primary and metastatic tissues revealed atypical genomic trajectories (TMB decrease, KRAS and SMAD4 regressive mutations), specific genetic events (ERBB2 point mutations) and scarce T-cell infiltration.

Prognostic and Predictive Role of CXC Chemokine Receptor 4 in Metastatic Colorectal Cancer Patients.

Background: Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. About 30% of patients present with metastatic disease involving predominantly the liver and a similar percentage will develop distant metastases later after removal of the primary tumor. In metastatic CRC, chemotherapies and biological drugs have prolonged survival for up to 30 months.

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol.

Background: Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients' selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).

Folfiri-Aflibercept vs. Folfiri-Bevacizumab as Second Line Treatment of RAS Mutated Metastatic Colorectal Cancer in Real Practice.

There are no clinical studies comparing the efficacy of bevacizumab vs.aflibercept in association with folfiri in RAS mutated (RAS-M) metastatic colorectal cancer patients (mCRC) pretreated with folfox and bevacizumab. Consecutive RAS-M unresectable mCRC patients progressing to first-line folfox/bevacizumab were treated with 12 cycles of folfiri/bevacizumab (arm A) or folfiri/aflibercept (arm B) at Oncologist discretion.

Updates on the Role of Molecular Alterations and NOTCH Signalling in the Development of Neuroendocrine Neoplasms.

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.

Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment.

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.

Integration of stereotactic radiotherapy in the treatment of metastatic colorectal cancer patients: a real practice study with long-term outcome and prognostic factors.

Background: There are very few clinical or prognostic studies on the role of SRT (Stereotactic Radiation Therapy) in the continuum of care of metastatic colorectal cancer (mCRC) patients.

Patients And Methods: Patients affected by oligo-mCRC were treated with SRT before or after front-line standard treatments. SRT was delivered according to a risk-adapted protocol.

Funds Reimbursement of High-Cost Drugs in Gastrointestinal Oncology: An Italian Real Practice 1 Year Experience at the National Cancer Institute of Naples.

The therapeutic scenario of Oncology is enriching of innovative agents which are determining an increase in public expenditure because of their high cost. In Italy, a web-based government Registry is used to monitor the clinical use of these drugs and, in later phases, to obtain funds reimbursement according to specific economic agreements with companies. A health policy expert Pharmacist was included in the multidisciplinary team of the Department of Abdominal Oncology of the National Cancer Institute (NCI) of Naples "G.

First Biologic Drug in the Treatment of RAS Wild-Type Metastatic Colorectal Cancer: Anti-EGFR or Bevacizumab? Results From a Meta-Analysis.

We performed a meta-analysis in order to analyze and quantify the effect on survival of starting therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC) patients with anti-EGFR agents or bevacizumab. Randomized, phase II or III, clinical trials reporting overall survival (OS) in RAS wt mCRC patients treated with first-line chemotherapy (CT) associated with bevacizumab or anti-EGFR agents were selected. The primary end-point of this meta-analysis was OS; findings were depicted in classical Forest plots.

Biotherapies in Solid Tumors: Are Negative Results Still of Low Priority for Publication?

In 2005, we performed the largest survey on clinical trials of biotherapies for all solid tumors and found indirect evidence of a publication bias: editors of medical journals were more prone to publish positive results independently from the quality of the studies. We collected data from 2003 to 2015 in 487 studies, and the publication bias previously described was not found in the years between 2010 and 2015: this could be related to changes and/or innovations in the guidelines and editorial policies of oncology journals occurred over the last years.

Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy.

Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage IIIb adenocarcinoma in May 2009. During follow-up he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography- computed tomography (PET-CT) scan and increase of carcinoembryonic antigen (CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012.

Nab-Paclitaxel and Gemcitabine in Advanced Pancreatic Cancer: The One-year Experience of the National Cancer Institute of Naples.

Background: Pancreas adenocarcinoma is the sixth cause of cancer-related death worldwide with an increasing mortality in the Western countries. Recently, the association between nab-paclitaxel (nab-P) and gemcitabine (GEM) has significantly improved progression-free and overall survival.

Patients And Methods: Patients affected by metastatic pancreas adenocarcinoma were treated at the Department of Abdominal Oncology of the National Cancer Institute of Naples from July 2015 to July 2016 with nab-P at 125 mg per square meter of body-surface area followed by GEM at 1,000 mg per square meter on days 1, 8 and 15 every 4 weeks.

Obesity and Cancer: Biological Links and Treatment Implications.

Obesity is an epidemic disease and correlates with cardiovascular diseases increasing the overall mortality. However, it has been recently demonstrated that cancer is an unexpected consequence of obesity. In most of the studies, it is evaluated with body mass index (BMI): high BMI increases cancer risk and reduces survival of many solid tumors.

Gemcitabine mono-therapy versus gemcitabine plus targeted therapy in advanced pancreatic cancer: a meta-analysis of randomized phase III trials.

Background: Prognosis of advanced pancreatic cancer is dismal and the novel targeted therapies, albeit successfully used to treat many advanced tumors, have shown modest results. We performed a meta-analysis in order to quantify the effect size on survival of adding targeted therapy to single agent gemcitabine.

Methods: Randomized phase III trials comparing gemcitabine mono-therapy versus gemcitabine plus a targeted agent in first-line treatment of advanced pancreatic cancer designed on survival as primary outcome were selected.

Antiangiogenic Therapy in Pancreatic Neuroendocrine Tumors.

In recent years, many progresses have been pursued in the management of advanced pancreatic neuroendocrine tumor (pNET); most of them were prompted by increasing knowledge of biology of these neoplasms, including the identification of promising biological targets for therapy. PNETs belong to a group of rare neoplastic diseases. They originate from neuroendocrine system cells and are very heterogeneous regarding anatomic localization and aggressiveness.

Diabetes and Body Mass Index Are Associated with Neuropathy and Prognosis in Colon Cancer Patients Treated with Capecitabine and Oxaliplatin Adjuvant Chemotherapy.

Background: There are few background data on the impact of clinical factors on neurotoxicity and prognosis in patients treated with adjuvant capecitabine and oxaliplatin (CAPOX) chemotherapy.

Methods: 102 stage II high-risk and stage III colorectal cancer patients were treated for 6 months with adjuvant CAPOX, then they were followed up. Associations between clinical variables, metabolic syndrome components, smoking and neurotoxicity were evaluated by the x03C7;2 test.

Everolimus and pancreatic neuroendocrine tumors (PNETs): Activity, resistance and how to overcome it.

Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors (PNETs) can be functional, hormone secreting tumors, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNETs, usually present later either incidentally or due to tumor bulk symptoms.