Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15–20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients’ overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor’s ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0786-0) contains supplementary material, which is available to authorized users.

Introduction: Psychological consequences of the COVID-19 pandemic include pandemic triggered feelings of fear, uncertainty, and anxiety added to the effects of restricting the population's activities in lockdown. Aim: We aimed to study the effect of COVID-19 pandemic on sexual satisfaction of females and males in Egypt and to evaluate possible predictive factors. Methods: Married men and females in Egypt were invited to respond to an online questionnaire. The questionnaire addressed medical history, socioeconomic status, sexual performance satisfaction before and during the lockdown in addition to validated Arabic questionnaires for depression, sexual function in males and females, and sexual satisfaction (Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Female Sexual Function Index, International Index of Erectile Function-5, Index of Sexual Satisfaction, respectively). Main outcome measure: The main outcome measures were frequency of depression, anxiety, sexual dysfunction, and sexual satisfaction in males and females during COVID-19 lockdown. Results: A total of 479 females and 217 males completed the questionnaire. Sexual satisfaction was significantly higher before (91.2%, 73.5%) than during lockdown (70.5%, 56.2%) in both males and females, respectively. During lockdown, significantly more males (70.5%) reported being satisfied with their sexual performance than females (56.2%) (P < .001). More than half of the male subjects (68.2%) had no erectile dysfunction while 97.3% females scored 26.5 on the Female Sexual Function Index scale suggestive of sexual difficulties. Sexual stress was significantly greater in females (70.8%) than males (63.1%). Educational level, occupation, anxiety, and erectile dysfunction were independently associated with sexual stress in males. Being a housewife or unemployed, husband's age >35 years, marriage duration of 5-10 years, anxiety, and female sexual dysfunction were predictors of sexual relation stress in females. Conclusion: COVID-19 pandemic was associated with lower sexual satisfaction in both genders. Females however suffered more anxiety and depression and thereby greater risk of sexual function difficulties and sexual dissatisfaction. Intervention strategies in order to lessen the suffering of affected individuals particularly after the pandemic are recommended.

The purpose of this phase I study was to determine the potential efficacy of adenoviral-mediated suicide gene therapy in women with recurrent ovarian cancer. Fourteen patients were treated intraperitoneally with herpes simplex virus-thymidine kinase (HSV-TK)-encoding adenovirus (AdHSV-TK) in dosages ranging between 1x10(9) and 1x10(11) pfu. Beginning 2 days later, ganciclovir (GCV) was administered intravenously at a dose of 5 mg/kg bid for 14 days. Transient vector-associated fever was experienced by 4 of 14 (29%) treated patients. Other possible vector-associated constitutional symptoms, abdominal pain, and gastrointestinal symptoms were experienced by 6 of 14 (43%) treated patients. No other dose-limiting vector-specific side effects were noted. Of the 13 patients evaluable for response, 5 (38%) had stable disease and 8 (62%) had evidence of progressive disease. Molecular analysis of evaluable ascites samples demonstrated the presence of transgene DNA and RNA in most patients 2 days following Ad HSV-TK administration. Ten of 11 evaluable patients had an increase in anti-adenovirus antibody titer. These results suggest that treatment with AdHSV-TK in combination with GCV is feasible in the context of human ovarian cancer and tolerated at the dosages studied.

Background. In Egypt more than one-third of colorectal cancer (CRC) cases occur in individuals aged 40 years and younger, and are diagnosed at advanced stages; currently, CRC screening is not done as a routine part of preventive care. To lay the foundation for the development of a CRC multilevel screening program in Egypt, this qualitative study aimed to explore the perspectives of Egyptian physicians. Materials and Methods. The PRECEDE-PROCEED model, which focuses on predisposing (intrapersonal), reinforcing (interpersonal), and enabling (structural) factors inherent in health behaviors, served as our theoretical framework. Primary health care physicians, oncologists, and gastroenterologists practicing in Alexandria, Egypt, participated in 1 one-hour semistructured interview. Interviews were audio recorded, transcribed, translated into English, and analyzed by thematic analysis. Results. Seventeen physicians participated (n = 8 specialists and n = 9 primary care physicians). Barriers to CRC screening included socioeconomic status, a lack of emphasis on prevention, fear, and cost (predisposing); a belief that only high risk patients should be screened and a lack of confidence in providers to perform and interpret screening tests appropriately (reinforcing); and cost, lack of availability of the tests, and inadequate training for laboratory technicians and providers (enabling). Potential facilitators included implementing a media campaign emphasizing early detection, curability and prevention (predisposing); educating physicians and eliciting physician engagement (reinforcing); and decreasing costs, making screening tests widely available, and providing well-trained providers (enabling). Conclusion. A CRC screening program is needed in Egypt, and to be successful it would likely need to address barriers at multiple levels. The Oncologist 2020;25:e1525-e1531 Implications for Practice: In Egypt, colorectal screening is not a routine part of preventive care, and colorectal cancer is often diagnosed at an advanced stage in individuals aged 40 years or younger. Screening can prevent and detect colorectal cancer in its early stages, but before designing any screening program, understanding the context is important as cultural beliefs may impact the acceptability of screening methods. By exploring the perspectives of Egyptian physicians, this study found important insights into how screening program components should be considered in the Egyptian culture and lays the foundation for the development of a multilevel colorectal screening program in Egypt.