All Articles

Guler Yavas^1*, Huseyin Yılmaz², Kaan Oysul³, Cagdas Yavas¹, Osman Vefa Gul¹, Cetin Celik⁴

^1*Selcuk University, Department of Radiation Oncology, Konya, Turkey

²Selcuk University, Department of General Surgery, Konya, Turkey

³Medicana International Ankara, Department of Radiation Oncology, Ankara, Turkey

⁴Selcuk University, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Konya, Turkey

The management of loco-regional recurrences from endometrial cancer is challenging since there are limited data regarding to management of recurrent endometrial cancer. Therapeutic options are often limited particularly for the patients who received adjuvant radiotherapy (RT). Patients who present with loco-regional recurrence after curative surgery and adjuvant RT are ideal for salvage surgery; However, the salvage surgery is associated with higher rates of mortality and morbidity. Re-irradiation could be an option for selected patients. However, pelvic re-irradiation is challenging and is often approached reluctantly by radiation oncologist due to the tolerance limits of nearby normal tissues which may lead severe chronic toxicities. Herein we report a case of recurrent endometrial cancer who underwent second re-irradiation in addition to multiple cytoreductive debulking surgery.

Erin Schwab¹, Justin A. Chen¹, Jasmine C. Huynh¹, Jingran Ji¹, Mili Arora¹, May Cho¹, Edward J. Kim¹*

¹Department of Internal Medicine, University of California Davis, USA

Based on the well-established importance of dysregulated apoptosis as a hallmark of cancer, there has been robust interest in development of targeted drugs to promote cancer cell apoptosis. A promising target for promoting apoptosis is the Bcl-2 family of proteins. Bcl-2 family proteins are crucial in maintaining balance between cell survival and death through regulation of apoptotic signaling pathways via pro-survival and pro-apoptotic family members. To date, there has been limited efficacy with Bcl-2 inhibition alone in clinical development with benefit restricted to hematologic malignancies. However, combination approaches to inhibition of Bcl-2 and other oncogenic signaling pathways have provided evidence for potential anti-tumor synergy. We review herein the current evidence for targeting Bcl-2 family proteins as a cancer therapeutic strategy across both hematologic and solid organ malignancies.

Qin Ye¹, Jiayang Liu², Ke Xie¹*

¹Department of Oncology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China

²State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China

The B7 family of proteins is commonly divided into three classes according to their structure and the type of receptor they bind to. The B7 proteins exhibit both positive and negative functions with regard to the immune response and are known to be co-inhibitory or co-stimulatory ligands that regulate antitumor immune responses. They are also involved in the regulation of cancer progression via non-immunological functions such as accelerating metabolism, promoting proliferation, and facilitating chemoresistance. Given the dynamic interaction between cancer cells and B7 family proteins, each member has been considered as a novel biomarker or therapeutic target that may well improve the effectiveness of cancer diagnosis and treatment. In this review, we summarize the characteristics of B7 proteins and their immunological and non-immunological roles in cancer progression.

Sonia Bouri¹, John P Martin¹

¹Charing cross hospital, Imperial College London

Iron deficiency anaemia (IDA) is a common condition. The finding of IDA should be given urgent attention as 8-15% of patients will be diagnosed with a gastrointestinal cancer and patients requiring urgent investigation should be identified. IDA is defined as a haemoglobin below the normal range with iron studies that indicate the presence of iron deficiency. This article will discuss the causes of IDA, interpretation of iron studies, and initial investigations for IDA. In the presence of infection or inflammation, the ferritin can be up to 100µg/l even in the presence of IDA and these patients should be considered as having IDA if the other iron studies are supportive. Patients of all ages with IDA should have urinalysis and a Coeliac screen. Patients above 60 years and symptomatic patients of any age should be offered a colonoscopy and gastroscopy within 2 weeks. Men and women younger than 60 years, who are asymptomatic can have routine colonoscopy and gastroscopy. Pre-menopausal women should undergo the relevant endoscopy if they have symptoms or a family history of cancer. If initial bi-directional endoscopies do not show cancer, cancer should be considered in patients who do not respond to iron supplementation, which can indicate ongoing blood loss from the small bowel, or from extra-gastrointestinal sources.

Sunjida Ahmed¹, Christopher Schwartz¹, M. Zahidunnabi Dewan¹, Ruliang Xu¹*

¹Department of Pathology, NYU Langone Medical Center, New York, NY 10016, USA

The transforming growth factor β (TGF-β) superfamily includes a group of structurally related cytokines that regulate a wide variety of biological processes. The diversity of its action depends on the dynamic tissue microenvironment, and interplays among the factors involving in the signaling pathway. Although its expression is tightly regulated in normal tissue, overexpression of TGF-β has been identified in multiple tumor types, including pancreatic adenocarcinoma. In pancreatic tumorigenesis, TGF-β acts initially as a tumor suppressor through phosphorylation and activation of SMAD4/DPC4 gene. Mutation of SMAD4/DPC4 gene results in carcinogenesis and tumor progression in many cancers like lung, colon, and pancreatic cancer. SMAD4 mutation is now recognized in >50% of pancreatic ductal carcinomas. This review is to evaluate the diagnostic and prognostic value targeting the TGF-β/SMAD4 pathway in pancreatic ductal adenocarcinoma.

Karen A Fitzner¹*, Milda Plioplys²

¹FH Consultants, 554 Hillcrest Dr, Sawyer, MI, USA

²Clinical & Human Research Protections, City of Hope, Duarte, CA, USA

A chapter, Impact of cost on the safety of cancer pharmaceuticals, by Fitzner and Oteng Mensah in a recent book, Cancer Policy: Pharmaceutical Safety¹, aims to inform readers about the economics associated with the interplay between safety, costs of cancer treatment, and outcomes of cancer care. That chapter includes a general discussion of safety-related costs, cancer care expenditures, and processes that aim to ensure drug safety. It also identifies the negative effects of the high cost of care on patients with cancer and their families. The authors’ focus on safety and cost of cancer pharmaceuticals, while appropriate for the book in which it appears, is limited. Pharmaceutical costs and their impact are only part of the safety story. A more holistic approach to thinking about patient safety can be constructive.

Bhaswati Sarcar¹, Xinqun Li², Jason B. Fleming¹*

¹Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, FL, USA

²Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, TX, USA

The extracellular matrix (ECM) in the tumor microenvironment (TME) has gained considerable interest in recent years as a crucial component in fundamental cellular processes and provides novel therapeutic targets. Lumican is a class II small leucine-rich proteoglycan with a key role in ECM organization and modulation of biological functions dependent on tumor type, abundance, and stage of disease. The presence of stromal lumican in the ECM surrounding pancreatic ductal adenocarcinoma (PDAC) inhibits cancer cell replication and is associated with improved patient outcomes after multimodal therapies. In this mini-review, we re-present our novel findings describing how hypoxia (1% O2) within the TME influences stromal lumican expression and secretion. We observed that hypoxia specifically inhibited lumican expression and secretion post-transcriptionally only from pancreatic stellate cells. Hypoxia-induced increased lactate production did not influence lumican expression. Notably, autophagy was induced by hypoxia in ex vivo cultures of patient-derived primary PDAC xenograft and pancreatic stellate cells; however, the cancer cells remain unaffected. Moreover, hypoxia-inducible factor (HIF)-1α expression or inhibition of AMP-regulated protein kinase (AMPK) activation within hypoxic stellate cells restored lumican expression levels. Interestingly, AMPK inhibition attenuated hypoxia-reduced phosphorylation of the mTOR/p70S6K/4EBP signaling pathway. The aim of this mini-review is to summarize our recent publication that hypoxia reduces stromal lumican in PDAC through autophagy-mediated degradation and reduction in protein synthesis within pancreatic cancer stellate cells. This may provide another plausible mechanism by which hypoxia-induced stromal autophagy leads to cancer growth.

Steven S. Coughlin^1,2*, Lee Caplan³, Jessica Lynn Stewart⁴, Lufei Young⁵

¹Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA

²Research Service, Charlie Norwood Veterans Administration Medical Center, Augusta, GA

³Morehouse College of Medicine, Department of Community Health and Preventive Medicine, Atlanta, GA

⁴College of Allied Health Sciences, Augusta University, Augusta, GA

⁵College of Nursing, Augusta University, Augusta, GA

Although they have been widely studied, important questions remain about the impact of breast cancer survivorship care plans on improving health outcomes. The goal of this article was to review published studies on the impact of cancer survivorship care plans on health outcomes and health care delivery among breast cancer survivors. A total of 111 article citations were identified in PubMed and non-duplicates in CINAHL. After screening the abstracts or full texts of these articles and reviewing the references of previous review articles, 7 studies met the eligibility criteria. All of the studies had a randomized controlled design. Early trials of the efficacy of breast cancer survivorship care plans generally showed little or no improvement in health outcomes. The positive findings of recent studies suggest that survivorship care interventions that empower and activate patients to self-manage their follow-up care and improve patient-provider communication may be especially promising.

Miao Guo¹, Wei Wu⁵, Wei Liu^{2, 3}*, Fu Ren^{2, 3, 4#}

¹Department of Clinical Laboratory, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, Liaoning, China

²Institute of Biological Anthropology, Jinzhou Medical University, No.40, Section 3, Songpo Road, Linghe District, Jinzhou 121001, Liaoning, China

³Liaoning Province Key Laboratory of Chinese Physical Characteristics Research (LPKL-CPCR), Jinzhou 121001, Liaoning, China

⁴Department of Anatomy, College of Basic Medical Sciences of Jinzhou Medical University, Jinzhou 121001, Liaoning, China

⁵School of Humanities and Management, Jinzhou Medical University, Jinzhou, Liaoning, China 121001

Glycoprotein A Repetitions Predominant (GARP), also known as leucine-rich repeats containing 32 (LRRC32), is a transmembrane protein that presents latent TGF-β1 on the surface of regulatory T cells (Tregs) and modulates its activation in tumor immunosuppressive environment. Tregs are immunosuppressive immune cells that play an important role in tumor development and progression. Inhibition of Treg function is considered to be an effective strategy for antitumor therapy. In addition to its expression in Tregs, GARP has been recently found to be highly expressed in a few types of human solid tumor tissues, yet the role of its expression in tumor tissues or cells remains unknown. Most previous studies on GARP have focused on GARP function in Tregs and the role of GARP in latent TGF-β1 activation. The present review provides an up to date overview of GARP expression and its potential role in tumor cells and tissues.

Efrossini D. Patsou¹, George T. Alexias¹, Fotios G. Anagnostopoulos¹, Michalis V. Karamouzis²*

¹Department of Psychology, Panteion University of Social and Political Sciences, Athens, Greece

²Medical School, National and Kapodistrian University of Athens, Athens, Greece

Breast cancer is the most common cancer affecting women worldwide. Women have many disturbing feelings and psychological side effects during diagnosis, treatment and survivorship which include depression, anxiety, low self-esteem and poor quality of life. The aim of the study was to examine the associations between physical activity, global health, quality of life, depressive symptoms, self-esteem, and anxiety in breast cancer survivors after finishing cancer treatment and through survivorship. Demographic variables such as marital status, education, and income, as well as cancer stage and level of physical activity were tested as predictors of depressive mood, anxiety, self-esteem and quality of life in 171 Greek breast cancer survivors.

We are presenting a commentary on the paper in order to highlight the most important conclusions of the study and suggest areas for further investigation.

Franziska Singer^1,2, Daniel J. Stekhoven^1,2*

¹NEXUS Personalized Health Technologies, ETH Zurich, Otto-Stern-Weg 7, 8093, Zurich, Switzerland

²SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland

Yingtian Wang, Ying Zhang, Jie Liu, Huiting Fan, Xueqian Wang, Hong-sheng Lin*

Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China

Shinji Atagi

Kinki-chuo Chest Medical Center, Osaka, Japan

As of now, concurrent chemoradiotherapy is the treatment of choice for locally advanced stage III non-small cell lung cancer (NSCLC). Older adults continue to be underrepresented in clinical trials, and studies designed specifically for this age group are rare. Prospective elderly-specific trials for locally advanced stage III NSCLC provide little evidence. Older patients are more susceptible to adverse events. A key question is whether elderly patients can receive the same treatments and derive the same benefit as their younger counterparts. The JCOG0301 demonstrated the clinically significant benefits of concurrent daily low-dose carboplatin and thoracic radiotherapies in elderly patients in comparison with those of radiotherapy alone. Recently, durvalumab therapy improved the progression-free survival of patients with unresectable stage III NSCLC whose disease had not progressed after concurrent chemoradiotherapy. Therefore, immune checkpoint inhibitors will also play an increasing role for elderly patients with stage III NSCLC. There are great differences between elderly individuals. Geriatric assessment is recommended to be incorporated in clinical trials. Furthermore, pragmatic clinical trials are required to establish clinical evidence for older patients with a broad range of conditions.

Steven S. Coughlin^1,2*, Lee Caplan³, Lufei Young⁴

¹Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA

²Research Service, Charlie Norwood Veterans Affairs Medical Center, Augusta, GA

³Morehouse College of Medicine, Department of Community Health and Preventive Medicine, Atlanta, GA

⁴College of Nursing, Augusta University, Augusta, GA

Background: Patient portals and other Internet-based technologies have been increasingly used to improve cancer care coordination. Patient portals may introduce special considerations in oncology populations where longitudinal outpatient care is often more intensive than in most other specialties.

Methods: This article, which is based upon bibliographic searches in PubMed, reviews the literature on web portal use by cancer patients. Articles published in English from 2000 to August 2018 were identified using the following MeSH search terms and Boolean algebra commands: web portal AND cancer. Information obtained from bibliographic searches (title and topic of article, information in abstract, and keywords) was used to determine whether to retain each article identified in this way.

Results: A total of 263 article citations were identified in the bibliographic searches. Of these, 10 met the eligibility criteria. A variety of study designs were used including focus groups, usability testing, in-person interviews, questionnaire surveys, retrospective cohort, and non-randomized trial. Cancer patients had reached modest levels of portal use. Increased portal use has been associated with younger age, white race, and higher socioeconomic status. Most cancer patients used portals to look up testing results and provide notes, but had difficulty in interpreting the results appropriately.

Conclusions: Our study adds to the growing evidence that patient portals play a significant role in promoting self-management in cancer survivors. Additional studies are needed to determine factors influencing portal use, so effective interventions can be developed to enhance portal use.

James E. Trosko

Department of Pediatrics/Human Development, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA

While the concept of “precision medicine” is not new, sophisticated technologies have led to a view that the data generated will provide individuals, physicians and public policy-makers with the information required to predict, intervene and protect against many diseases. However, without understanding of the underlying molecular mechanisms, such as the mutagenicity, cytotoxicity or epigenetic alterations, induced by agents to which a human has been exposed, and with pathogenic events, such as birth defects, cardiovascular disease, cancer, immune responses, and reproductive or neurological diseases, there will be no “precision”. The aim of this “Commentary” is that, while mutations and cell death contribute to human diseases, including cancers, the toxicity of chemicals is primarily due to epigenetic effects on human organ-specific adult stem cells. From the perspective of biological evolution, the transition from single- to multi-cellular organisms, along with the generation of new genes and cellular processes, led to the evolution of Homo sapiens and “cultural evolution”. This transition has created a “collision” of the slow biological evolution of genes that are important for survival in various environments, with extremely fast cultural evolution. This has occurred when cultural evolution has provided new means of migration for both people and foods, as well as new methods of agriculture and food production/distribution/processing. The population explosion, ecological alterations, global climate changes, and worldwide economic disparities all have a bearing on how the increases in median life span and the incidence of chronic metabolic diseases are managed in the face of globally limited healthcare resources.

Joseph A. Di Como¹, Christina W. Lee², Sharon M. Weber²*

Department of Surgery, Conemaugh Memorial Medical Center, Johnstown PA, USA

Department of Surgery, University of Wisconsin, Madison WI, USA

Igor M. A. Melo, Eliane A. Ribeiro, Renata A. Canevari*

Laboratório de Biologia Molecular do Câncer, Instituto de Pesquisa & Desenvolvimento (IP&D), Universidade do Vale do Paraíba (UNIVAP), São José dos Campos, São Paulo, Brasil

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and several studies have proven the close relationship between HPV and the development of cervical cancer. Several tests are currently performed for early and reliable diagnosis, in which the cervical cytology evaluation by the Papanicolaou method is highlighted. However, errors in the collection and misinterpretation of cell differentiation degree in smear by the pathologist result in incorrect or inaccurate results. Considering these points, it is of utmost importance to develop new technologies that perform accurate and reliable diagnosis and that present financial advantages and accessibility. Currently, molecular biology assays are excellent detectors of viral DNA, but it presents disadvantages, such as the need for high financial resources to gain access. Therefore, this review has the objective of highlighting the main diagnostic techniques that are already being used, such as specific kits for the detection of high-risk HPVs, or methodologies that are still in the study phase, but which already present good results, such as the application of physical FTIR spectroscopy principles and ultrasensitive biosensors.

Maryam Ghotbaddini, Vivian Moultrie, Joann B. Powell*

Clark Atlanta University- Center for Cancer Research and Therapeutic Development 223 James P. Brawley Drive Atlanta, Georgia, USA

Research on the aryl hydrocarbon receptor (AhR) has largely focused on its activation by various environmental toxins. Consequently, only limited inferences have been made regarding its constitutive activity in the absence of an exogenous ligands. Evidence has shown that AhR is constitutively active in advanced prostate cancer cell lines which model castration resistant prostate cancer (CRPC). CRPC cells can thrive in an androgen depleted environment. However, AR signaling still plays a major role. Although several mechanisms have been suggested for the sustained AR signaling, much is still unknown. Recent studies suggest that crosstalk between constitutive AhR and Src kinase may sustained AR signaling in CRPC. AhR forms a protein complex with Src and plays a role in regulating Src activity. Several groups have reported that tyrosine phosphorylation of AR protein by Src leads to AR activation, thereby promoting the development of CRPC. This review evaluates reports that implicate constitutive AhR as a key regulator of AR signaling in CRPC by utilizing Src as a signaling intermediate.

Xiao Wang*, Yin Zhang, Ning Yue, Ke Nie

Department of Radiation Oncology, Rutgers-Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA

In treating locally advanced non-small-cell lung cancer (NSCLC), radio-tolerance of the normal lung often limits the amount of dose that can be delivered to the primary cancer site. Radiation-related pneumonitis (RP) and other normal lung tissue complications have a significant impact on clinical outcome and patient quality of life. How to minimize treatment side effects while achieving desirable local control of lung cancers has been a continuous challenge.

Functional imaging-guided radiotherapy, which can achieve a local boost of primary cancer site or functional avoidance of normal organs, has been increasingly utilized in clinics. Various imaging approaches have been employed to achieve functional imaging guidance and implemented in different treatment regimens. There are several on-going clinical trials aiming to evaluate the clinical outcomes that are utilizing functional imaging-guided photon radiation to spare the high functioning portions of the lungs. The main applications of functional imaging-guided radiotherapy in the management of NSCLC patients will be discussed in this review.

Sung Wan Kim^1,2*, Joung-Pyo Nam^1,2, Soyoung Kim^1,2, Yong Kiel Sung^1,2,3

Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA

Center for Chemically Controlled Delivery, University of Utah, Salt Lake City, Utah 84112, USA

Department of Chemistry, Dongguk University, Phildong-ro 1 Gil, Chung-gu, Seoul 04620, Korea

The design of a gene delivery system requires a complete understanding of the interaction between targeting cell and delivery systems. The poly(cystaminebis- (acrylamide)-diaminohexane) (poly(CBA-DAH)) has been confirmed as a bio-reducible efficient delivery carrier among the various systems. Poly(ethylenimine) (PEI, 1.8?kDa) was conjugated to poly(CBA-DAH) via a disulfide bond. The PEI conjugated poly(CBA-DAH) (PCDP) was able to bind with pDNA at a very low molecular weight ratio and form the polyplexes with nano-size and positive surface charge. To confirm the transfection efficiency, the plasmid DNA encodes with the luciferase reporter gene and green fluorescent protein reporter gene have made to use a bio-reducible efficient gene delivery. The PCDP polyplexes show 10 times higher gene transfection efficiency than Lipofectamine® polyplexes in bio-mimic in vivo condition. It has been reviewed that the bio-reducible PEI(1.8kDa) conjugated poly(CBA-DAH) is finally concluded as an efficient gene delivery carrier.

Ting-Hsuan Yang^1,2, Ren-Jun Hsu², Wen-Hsin Huang¹, An-Rong Lee¹*

School of Pharmacy, National Defense Medical Center, No. 161, Section 6, Mingchuan East Road, Taipei 11490, Taiwan

Tri-Service General Hospital Biobank, No.325, Sec. 2, Chenggong Rd. Taipei 11490, Taiwan

Cancer cells are characterized by uncontrolled proliferation after escaping from inherent physiological constraints on growth and survival and by destructive invasion of the healthy surrounding tissues. Many kinases involved in signal transduction are overactive in malignant tumor cells. Thus, pharmacotherapeutic interventions targeting kinases responsible for signal transduction of cancer hallmarks have become promising in developing novel anticancer agents. Pyrrole indolin-2-one (or pyrrole oxindole, 1), a lead scaffold of kinase inhibitors, is used for anti-angiogenesis via inhibiting vascular endothelial growth factor receptors (VEGFs) and platelet-derived growth factor receptors (PDGFRs). The kinase selectivity and inhibitory activity of pyrrole indolin-2-one 1 can be significantly influenced through structural modifications. This mini-review provides a detailed overview of structural modification of pyrrole indolin-2-one derivatives for the development of novel kinase inhibitors.

Xue Li¹, Chun Yang², Xiangyan Ruan¹, Stéphane Croteau², Pierre Hardy²*

¹Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China

²Departments of Medicine, Pediatrics, Pharmacology and Physiology, University of Montreal, Montreal, Quebec, Canada

Despite all our efforts, breast cancer remains a major public health problem threatening women’s health all around the world. The morbidity of breast cancer is rising in most countries and is going to rise further over the next 20 years. Hormone treatment is widely used and it is the most efficient method of reducing menopausal symptoms or preventing abortion and pregnancy. However, multiple studies have demonstrated that hormones, especially synthetic progesterone, remain an indisputable risk factor for breast cancer. MicroRNAs are a group of endogenous small non-coding single strand RNAs which play regulatory roles in the initiation, development, and progression of different types of cancer. Evidence from multiple sources indicates that microRNA-181a exerts anti-breast cancer effects by inducing cancer cell death and preventing tumor invasion, infiltration and metastasis, etc. Our recent studies revealed that microRNA-181a not only suppresses breast cancer MCF-7 cell growth but also abrogates progestin-provoked cell growth. In this review, several interesting aspects of hormone replacement therapy and the role of microRNA-181a during progestin treatment are discussed.

Ofer Purim^1*, Aron Popovtzer², Ron Epelbaum³

¹Oncology Institute, Assuta Ashdod Academic Hospital, Ashdod, Israel

²Institute of Oncology, Davidoff Center, Rabin Medical Center, Petah Tikva, Israel, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

³Department of Oncology, Rambam Health Care Campus, Haifa, Israel

In the last 20 years, cancer treatment has witnessed a paradigm shift with the advent of modern targeted therapies. Still, at present, targeted therapies, despite being very effective, are only relevant for a minority of patients, whereas the majority of patients are still being offered cytotoxic drugs. The goal of this mini-review is to describe the clinical utility of tumor multi-panel molecular profiling (MMP) to guide treatment decisions (primarily chemotherapies but also targeted therapies) in patients with solid tumors and the evidence supporting this approach, focusing on the Caris Molecular Intelligence (CMI) MMP. The evidence suggests that MMP is a practical, implementable tool that can be used to personalize treatment (including that of chemotherapies), increasing the likelihood of response and sparing patients from unnecessary toxicity associated with ineffective therapies. MMP provides the ability to offer therapy to patients in later lines, particularly for those who have already failed multiple lines of therapy and exhausted the standard therapy options (by suggesting therapies which may be used off-label). Furthermore, the evidence indicates that MMP-guided therapy favorably impacts both progression-free survival and overall survival. As the current data consist of mainly retrospective studies, prospective trials are warranted to strengthen the evidence.

Frank E Mott^1*, Ruth L. Sacks²

¹Thoracic and Head/Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Texas, USA

²University of Texas MD Anderson Cancer Center, Texas, USA

Standard treatment of locally advanced nasopharyngeal carcinoma is patterned after the Intergroup 0099 trial with concurrent cisplatin with radiotherapy, followed by consolidation chemotherapy. This remains the guideline recommended standard. With the wider use of intensity modulated radiotherapy and the incorporation of taxanes in the chemotherapy regimen, many oncologists are increasingly using an induction approach with chemotherapy followed by concurrent chemoradiotherapy. Induction chemotherapy is not considered a standard approach despite studies showing efficacy and tolerability. In this mini-review, we summarize the data from trials and reviews of induction therapy and argue for its recognition as a viable standard option for patients with locally advanced nasopharyngeal carcinoma.

Rania Gaber^1,2,3, Torsten Goldmann^1,3*

¹Pathology of the University of Lübeck and the Research Center Borstel, Site Borstel, Clinical and Experimental Pathology, Borstel, Germany

²Department of Pathology, Faculty of Medicine, Alexandria University, Alexaandria, Egypt

³Airway Research Center North (ARCN), Member of the German Center for Lung Research, Germany

Epidermal growth factor receptor (EGFR) is a predictive biomarker in many solid cancers including non-small cell lung carcinoma (NSCLC). Patients’ responsiveness to therapy is based on the prior determination of EGFR status. Many techniques were used to detect the potential predictive biomarker and considered as gold standards based on molecular genetic techniques as direct sequencing and polymerase chain reaction (PCR). Immunohistochemistry (IHC) using EGFR mutation-specific antibodies were generated as an alternative simple tool to identify EGFR status and its response to tyrosine kinase inhibitors (TKIs). EGFR gene copy number and wild-type EGFR are other parameters which determine the response to TKIs. The aim of this mini-review is to analyze the studies which investigated the IHC EGFR mutation-specific antibodies, in lung adenocarcinoma (ADC), to determine its accuracy and reliability as a pre-selection tool for candidate patients for TKIs therapy as well as the interplay with other EGFR biomarkers which are EGFR gene copy number and the wild-type EGFR in lung NSCLC. The later determine the response to TKIs and their detection methodology is standardized making them good candidates for comparison with the EGFR-mutation.