Evaluation of Anti-Angiogenic Therapy Combined with Immunotherapy and Chemotherapy as a Strategy to Treat Locally Advanced and Metastatic Non-Small-Cell Lung Cancer.

Immunotherapy has made recent improvements in disease-free survival (DFS) and/or overall survival (OS) in all stages of non-small-cell lung cancer (NSCLC). Here, we review the tumor microenvironment and its immunosuppressive effects and discuss how anti-angiogenic therapies may potentiate the anti-carcinogenic effects of immunotherapy. We also review all the past literature and discuss strategies of combining anti-angiogenic therapy and immunotherapy +/- chemotherapy and hypothesize how we can use this strategy for non-small-cell lung cancer in metastatic previously untreated/previously treated settings in previously treated EGFR-mutated NSCLC for the upfront treatment of brain metastases prior to radiation therapy and for the incorporation of this strategy into stage III unresectable disease.

Precision therapeutic targeting of human cancer cell motility.

Increased cancer cell motility constitutes a root cause of end organ destruction and mortality, but its complex regulation represents a barrier to precision targeting. We use the unique characteristics of small molecules to probe and selectively modulate cell motility. By coupling efficient chemical synthesis routes to multiple upfront in parallel phenotypic screens, we identify that KBU2046 inhibits cell motility and cell invasion in vitro.

Adjuvant Sunitinib in High-Risk Patients with Uveal Melanoma: Comparison with Institutional Controls.

Purpose: To compare overall survival in high-risk patients with primary uveal melanoma who received adjuvant sunitinib with institutional controls.

Design: Retrospective cohort.

Participants: Selection criteria were (1) monosomy 3 and 8q amplification by cytogenetic or DecisionDx-UM Class 2 and (2) monosomy 3 and large tumor size (T3-4 by American Joint Committee on Cancer classification).

Immune Check Point Inhibitors Combination in Melanoma: Worth the Toxicity?

The combination of immune checkpoint inhibitors ipilimumab and nivolumab has been recently been FDA approved for first line treatment of unresectable and metastatic BRAF wild type melanoma. The approval came following the impressive results of the CheckMate 067, where the combination of ipilimumab and nivolumab appeared to outperform each as a single agent in regards to response rate and progression free survival. Though we await final overall survival data, the combination will likely be adapted by many oncologists and integrated into the ever changing melanoma treatment algorithm.

Immunotherapy for Non-Small Cell Lung Cancer - Finally a Hint of Hope.

Lung cancer is a major public health problem worldwide and the leading cause of cancerrelated mortality in developed countries. Significant advances have been made especially with the discovery of targeted agents. However, only a small proportion of patients carry activating mutations; until recently conventional chemotherapy and angiogenesis inhibitors were the preferred treatment for the vast majority of patients.

What is the Current Role of Immunotherapy for Colon Cancer?

Colon cancer is a leading cause of cancer related mortality. Until very recently the only existing options that medical oncologists had to treat metastatic colon cancer were a combination of chemotherapy, anti-EGFR and anti-angiogenic agents. We currently have the first proof that immune therapies could be an effective approach to battle colorectal cancers that carry a mismatch repair machinery deficient phenotype.

Anti-Hormonal Therapies for Premenopausal Patients--What did we Learn from the TEXT/SOFT Trials?

Between 20-25% of all breast cancers are diagnosed in patients younger than 50 years of age, most of whom are still premenopausal. Currently, tamoxifen is considered the standard of care for adjuvant treatment in these cases. However, in postmenopausal women, aromatase inhibitors (AIs) are a better choice.

Role of Anti-HER-2 Therapies in the Neo-Adjuvant Setting: Is Complete Pathological Response a Solid Surrogate?

Breast cancer continues to be a major health problem. Both patients and clinicians demand faster access to drugs that could result in better outcomes. In part motivated by this necessity, there has been a change in the dominant paradigm regarding how drugs become approved.

Role of Carboplatin in the Treatment of Triple Negative Early- Stage Breast Cancer.

Triple negative breast cancer (TNBC) is more prevalent in younger patients and those carrying BRCA mutations. Although the incidence of breast cancer in general has dropped during the last years, TNBC has shown a relative increase. It is recognized as a breast cancer subtype with a high risk of tumor relapse and mortality.

Successes and setbacks of early investigational drugs for melanoma.

Treatment of advanced and metastatic melanoma is a rapidly changing field. Over the past 10 years, there have been six new drugs approved by the FDA for the treatment of metastatic melanoma. These approved drugs include a number of immune checkpoint inhibitors and MAPK-pathway-targeted therapies.

Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases.

Purpose: To investigate the effects of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with uveal melanoma (UM) with liver-only metastasis.

Materials And Methods: In this double-blind phase II clinical trial, patients were randomized to undergo immunoembolization or bland embolization (BE). Lobar treatment was performed with GM-CSF or normal saline solution mixed with ethiodized oil followed by embolization with gelatin sponge emulsified with iodinated contrast medium.

Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions.

During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 over-expressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice.

Advances and new perspectives in the treatment of metastatic colon cancer.

During the last decade we have witnessed an unprecedented outburst of new treatment approaches for the management of metastatic colon cancer. Anti-angiogenic drugs, epidermal growth factor receptor blockers and multi-kinase inhibitors have all resulted in small but consistent improvement in clinical outcomes. However, this progress has paradoxically leaded us into new challenges.

Recent treatment advances and novel therapies in pancreas cancer: a review.

Purpose: Over the last couple of years, we have witnessed the availability of a wide variety of different therapeutic agents and the identification of effective combinations of existing ones that have transformed the way we approach and treat pancreatic cancer. Proof of this are the recent validations that combinations of conventional chemotherapy drugs, the FOLFIRINOX regimen and gemcitabine plus nab-paclitaxel, significantly improves clinical outcomes in patients with metastatic disease. However, deeper and more sophisticated understanding of the biology of this cancer as well as the ability to develop better and perhaps more precise drugs predict that the landscape may be changing even more.

The potential role of sunitinib targeting melanomas.

Introduction: Metastatic melanoma - independently of its cutaneous, uveal or mucosal origin - represents an exceptionally aggressive tumor with poor prognosis. Molecular and genetics investigations permitted to identify several important driver mutations: BRAF, NRAS, c-Kit, GNA11 and GNAQ. Additionally, hypervascular and immunlogenic characteristics of metastatic melanoma make in this tumor a unique therapeutic target.

Somatostatin receptor scintigraphy in patients with metastatic uveal melanoma.

As uveal melanoma originates in the neural crest, we aimed to explore whether somatostatin receptor (SSTR) expression is present and plays any role in these patients. Heavily pretreated metastatic uveal melanoma patients were tested with somatostatin receptor scintigraphy (SRS). Planar images of the whole body complemented by single-photon emission computed tomography on suspected sites were acquired between 4 and 24 h after an intravenous administration of 185-222 MBq (5-6 mCi) of indium-octeotride.

RB-pathway disruption is associated with improved response to neoadjuvant chemotherapy in breast cancer.

Purpose: We sought to determine whether dysregulation of the retinoblastoma (RB) tumor suppressor pathway was associated with improved response to neoadjuvant chemotherapy in breast cancer.

Experimental Design: An RB-loss signature was used to analyze the association between pathway status and pathologic complete response in gene expression datasets encompassing three different neoadjuvant regimens. Parallel immunohistochemical analysis of the RB pathway was conducted on pretreatment biopsies to determine the association with pathologic response to neoadjuvant chemotherapy.

Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline.

Purpose: The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma.

Methods: A comprehensive systematic review of the literature published from January 1990 through August 2011 was completed using MEDLINE and EMBASE. Abstracts from ASCO and SSO annual meetings were included in the evidence review.

Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline.

Purpose: The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma.

Methods: A comprehensive systematic review of the literature published from January 1990 through August 2011 was completed using MEDLINE and EMBASE. Abstracts from ASCO and SSO annual meetings were included in the evidence review.

Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?

Background: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce.

Methods: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues.

Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma.

Background: The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and insulinlike growth factor 1 receptor (IGF-1R) proteins and IGF-1R gene copy numbers in pancreatic ductal adenocarcinoma in relation to patients' characteristics and prognosis.

Methods: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue derived from tumor specimens recovered during surgery. Slides were evaluated for membranous EGFR and IGF-1R staining using both the HercepTest and the semiquantitative H-score systems.