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Abstract Cancer is one of the foremost causes of mortality. The human genome remains stable over time. However, human activities and environmental factors have the power to influence the prevalence of certain types of mutations. This goes to the excessive progress of xenobiotics and industrial development that is expanding the territory for cancers to develop. The mechanisms involved in immune responses against cancer are widely studied. Genome editing has changed the genome‐based immunotherapy process in the human body and has opened a new era for cancer treatment. In this review, recent cancer immunotherapies and the use of genome engineering technology are largely focused on.

Triple-negative breast cancer (TNBC) is a breast malignancy with a poor prognosis and limited therapeutic options. Many studies show that TNBC exhibits heterogeneity across clinical, histopathological, and molecular levels. In this review, we discuss the immunogenic features of TNBC with a focus on immunotherapy and the current standard of care in the neoadjuvant, adjuvant, and metastatic setting. In addition, we address the ongoing research on immunotherapy, antibody-drug conjugates (ADCs), poly ADP-ribose polymerase (PARP) inhibitors, and future challenges in the treatment of this entity.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is a subtype of BC that has been recently recognized as a separate clinical entity with distinct clinical and molecular characteristics. It is defined by a low level of HER2 protein expression, which distinguishes it from other more aggressive BC subtypes. Early studies suggest that it may have a more favorable prognosis than HER2-positive BC, as it is less likely to spread to other parts of the body and may be more responsive to standard BC treatments such as chemotherapy, radiation therapy, and hormone therapy. Given the relative new emergence of HER2-low BC, there is still much to be learned about this subtype; ongoing research is focused on identifying the underlying genetic mutations that contribute to HER2-low BC as well as developing targeted therapies that can improve outcomes for patients with this disease. This review is aimed at summarizing the current clinical knowledge on HER2-low BC, with the aim of creating a better understanding of this entity and paving the way for potential interventions and a new standard of care.

Aim: Bone tumors are rare and have an uneven geographic distribution. Methods: 730 patients diagnosed with bone tumors were included in this retrospective analysis. Results: With a 64% rate of malignancy, the most common tumors were metastasis (40%) mostly in the axial skeleton, Osteosarcoma (9%) mostly in the femur, Osteochondroma (8%) mostly in the femur, giant cell tumors (7%) mostly in the knee, and Ewing's sarcoma (6%) mostly in the axial skeleton. Conclusion: Even though a some of the tumors have a predilection for certain localizations in the human body, they may differ in the middle-eastern population. One must also pay attention to the higher rates of malignancies as compared with other cohorts.

Abstract Background Bladder cancer (BC) is the 10th most frequent tumor worldwide. Evidence shows an association between elevated risk of BC and various single nucleotide polymorphisms (SNP). BC incidence was the highest in Lebanon according to Globocan 2018 report, but little is known about the genetic susceptibility of Lebanese people to this disease. We aim to evaluate whether this prominent incidence of BC in Lebanon is attributable to known coding genetic variants. Methods A case-control study was conducted at Hotel-Dieu de France Hospital, Beirut. A cohort of 51 Lebanese patients with BC were recruited between 2017 and 2020. Whole Exome Sequencing (WES) was performed on peripheral blood samples to detect coding genetic variants in the patients. An in-house database including WES data from 472 Lebanese individuals served as control. Literature review of the genetic predisposition to BC was conducted to establish a database of variants known to influence the risk of BC. In-common SNPs were identified between cases and the aforecited database, and their allelic frequencies was quantified in the former and in controls. Comparative analysis of the allelic frequencies of each in-common SNP was carried out between cases, controls, and the genome aggregation database (gnomAD). Analysis was performed by applying the binomial law and setting the p-value to 10− 10. Results 484 polymorphisms associated with BC were extracted from the literature review ;151 of which were in-common with the 206 939 variations detected by WES in our cases. Statistically significant differences (p-value

Treatment of non-small-cell lung cancers (NSCLC) has evolved over the last decade. According to studies, the use of targeted therapies has significantly increased the life expectancy of patients. Moreover, ALK-tyrosine kinase inhibitors (ALK-TKIs) have improved clinical outcomes. In Lebanon, translating recommendations into clinical practice remains challenging. A Lebanese expert panel of oncologists was convened to describe the management paradigm and the clinical evidence supporting the optimal use of next-generation TKIs in patients with ALK-rearranged NSCLC and to provide an expert overview of local challenges and recommendations for optimizing the management of advanced NSCLC in Lebanese patients. The experts agreed that these recommendations should be part of a healthcare strategy to be implemented at the national level. Article highlights ALK-TKIs: ALK-tyrosine kinase inhibitors NSCLC: Overview of NSCLC management Over the last decade, non-small-cell lung cancers (NSCLC) management has evolved and is now based on genetic alterations, including ALK rearrangements. The use of ALK-tyrosine kinase inhibitors (ALK-TKIs) has changed the management paradigm for advanced NSCLC. Recommendations of NSCLC management in Lebanon Diagnosis: NGS testing should be preferred over sequential testing to identify several actionable targets, especially in young patients, light smokers, or non-smokers with squamous or mixed histology. Treatment: Due to limitations or unavailability of certain treatments, patients can either be encouraged to enroll in clinical trials or receive a first-generation ALK inhibitor that is always available, instead of a third-generation drug that is extremely potent but may pose a high risk of relapse if given intermittently. Panel experts agreed that lorlatinib would be the treatment of choice in patients with brain metastases. In other patients, clinicians would opt for any ALK-TKI. Patients with advanced NSCLC should have a systematic follow-up every 4–6 months, including brain magnetic resonance imaging (MRI). Patients who develop drug resistance following ALK-TKI treatment should be offered a rebiopsy or a liquid biopsy. MDT-based multimodal approach should be implemented for the management of NSCLC. Managing toxicity: Most adverse events resolve without any intervention. For grade I adverse events (AEs), neither dose reduction nor withholding treatment is necessary. However, for grade II or above AEs, the dose should be reduced and in cases where a severe AE re-occurs, treatment must be stopped and the patient monitored for recovery. For cognitive dysfunction, physicians should rule out any potential causes of Central nervous system (CNS) impairment before attributing it to lorlatinib treatment. Limitations in the Lebanese practice Several challenges are currently affecting Lebanese practice, including a deteriorating healthcare system, limited access to biomarker testing, high costs associated with diagnosis and treatment and shortages in medication and equipment. [ABSTRACT FROM AUTHOR]

Aim: Pancreatic adenocarcinoma is a very aggressive type of cancer, in which targeted therapies have not yet been fully utilized. KRAS wild-type pancreatic adenocarcinoma tumors are associated with different genomic alterations in comparison to KRAS mutated pancreatic adenocarcinoma. Objective: This systematic review aims to provide a one-stop summary of all these alterations, their proposed targeted treatment and their effect on disease progression. Methods: An electronic search strategy was elaborated in the PubMed database between 2020 and January 2024. Results: 21 studies were included, and we found that the most frequent targetable genomic alterations in KRAS wild-type pancreatic adenocarcinoma were BRAF, EGFR, FGFR, MSI-H/dMMR, Her2/ERBB2 amplification, BRCA1/2 and other HRDs, and gene fusions like ALK, NTRK and NRG1. Article highlights Standard of care for pancreatic ductal adenocarcinoma has been mediocre at best with very short median survival times. KRAS wild-type (WT) pancreatic ductal adenocarcinoma is less frequent but presents different and more targetable alterations than KRAS mutation (KRASm) pancreatic ductal adenocarcinoma. Different genomic alterations present in KRAS WT patients include BRAF, FGFR, EGFR, Her2 amplification, BRCA1/2 and HRD mutations, and MSI-H and dMMR tumors. These genomic alterations are targetable, some already with US FDA approvals. However, further testing is needed to prove and improve its efficacy in pancreatic ductal adenocarcinoma. Low frequency of KRAS WT pancreatic ductal adenocarcinoma patients is the main limitation to studies and advancements. Different genomic profiling techniques (liquid biopsy vs echo-guided endoscopic fine needle aspiration) are emerging, as well as different gene panels used in the profiling by different institutions, further contributing to divergences between studies, thus making progress harder. Age of onset of pancreatic ductal adenocarcinoma is another factor contributing to controversial results. Tumor mutational burden (TMB) is another source of controversy as some studies show higher mean TMB in KRAS WT pancreatic ductal adenocarcinoma patients compared with KRASm pancreatic ductal adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates (ADCs) have recently emerged as a promising therapeutic option that combine the specificity of monoclonal antibodies and the cytotoxic effect of chemotherapy. With numerous ADCs approved and on the market, a particular concern of ADCs that target HER-2 has been their cardiac side effects, in view of the crucial role of HER-2 in cardiac development and physiology. While rarely toxic and generally safe, numerous publications have outlined the consistent association of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) with the development of cardiac toxicity. Despite not being clinically relevant in most cases, cardiac baseline evaluation, monitoring and early detection of cardiac adverse events remain pivotal with HER-2 targeting ADCs. This review aims to summarize and better characterize the complete cardiac toxicity profile of HER-2 ADCs, with the goal of improving clinical understanding of this adverse event, leading to better recognition, monitoring and management. [ABSTRACT FROM AUTHOR]

Abstract Background Basal cell carcinoma (BCC) represents by far the most common non-melanoma skin cancer (NMSC) in the world with an increasing incidence of 3% to 10% per year, especially in patients under the age of 40. While variants in the sonic Hedgehog and cell cycle regulation pathways account for the majority of BCC cases in adults, the molecular etiology of BCC in young patients is unelucidated yet. This study aims to investigate the molecular profile of BCC in the young population. Methods 28 tumors belonging to 25 Lebanese patients under the age of 40, presenting different stages of BCC and diagnosed at Hôtel Dieu de France—Saint Joseph University Medical Center were included in this study. A selected panel of 150 genes involved in cancer was analyzed by Next Generation Sequencing (NGS) in the 28 included tumors. Results Genetic variants detected in more than 5% of the reads, with a sequencing depth ≥ 50x, were selected. Two hundred and two genetic variants in 48 different genes were detected, with an overall average sequencing depth of 1069x. Among the 28 studied tumors, 18 (64.3%) show variations in the PTCH1 gene, 6 (21.4%) in TP53 and 3 (10.7%) in SMO. Conclusions This is the first study reporting NGS-based analysis of BCC in a cohort of young patients. Our results highlight the involvement of the hedgehog and cell cycle regulation pathways in the genesis of BCC in the general population. The inclusion of a larger cohort of young patients is needed to confirm our findings.

Triple‐negative breast cancer (TNBC) is a breast malignancy with a poor prognosis and limited therapeutic options. Many studies show that TNBC exhibits heterogeneity across clinical, histopathological, and molecular levels. In this review, we discuss the immunogenic features of TNBC with a focus on immunotherapy and the current standard of care in the neoadjuvant, adjuvant, and metastatic setting. In addition, we address the ongoing research on immunotherapy, antibody‐drug conjugates (ADCs), poly ADP‐ribose polymerase (PARP) inhibitors, and future challenges in the treatment of this entity. [ABSTRACT FROM AUTHOR]

PURPOSEFertility and pregnancy-related issues are highly relevant for young (≤ 40 years) patients with breast cancer. Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding these issues.METHODSA 19-item questionnaire adapted from an international survey exploring issues about fertility preservation and pregnancy after breast cancer was sent by e-mail between November 2019 and January 2020 to physicians from LMICs involved in breast cancer care. Descriptive analyses were performed.RESULTSA total of 288 physicians from Asia, Africa, America, and Europe completed the survey. Median age was 38 years. Responders were mainly medical oncologists (44.4%) working in an academic setting (46.9%). Among responders, 40.2% and 53.8% reported having never consulted the available international guidelines on fertility preservation and pregnancy after breast cancer, respectively. 25.0%, 19.1%, and 24.3% of responders answered to be not at all knowledgeable about embryo, oocyte, or ovarian tissue cryopreservation, respectively; 29.2%, 23.6%, and 31.3% declared that embryo, oocyte, and ovarian tissue cryopreservation were not available in their countries, respectively. 57.6% of responders disagreed or were neutral on the statement that controlled ovarian stimulation can be considered safe in patients with breast cancer. 49.7% and 58.6% of responders agreed or were neutral on the statement that pregnancy in breast cancer survivors may increase the risk of recurrence overall or only in those with hormone receptor–positive disease, respectively.CONCLUSIONThis survey showed suboptimal knowledge, practice, and attitudes of physicians from LMICs on fertility preservation and pregnancy after treatment completion in young women with breast cancer. Increasing awareness and education on these aspects are needed to improve adherence to available guidelines and to promote patients' oncofertility counseling.

Aim: Assess the knowledge and behavior of Lebanese parents when it comes to melanoma and its prevention in children. Methods: A survey, to be completed by parents, was sent through children from three schools. Results: During sun exposure only 23.5% of 1012 respondents were always covering enough areas of their children's skin and 74.1% did not always apply sunscreen to their children. Parents of private school children were three times more likely to apply sunscreen to their children when exposed to sun, four times more likely to reapply sunscreen every 2–3 h and 21 times more likely to use a higher sun protection factor. Conclusion: Sun protection in children is insufficient and sunburns are frequent, illustrating the need for melanoma awareness campaigns.

Human epidermal growth factor receptor 2 (HER2)‐low breast cancer (BC) is a subtype of BC that has been recently recognized as a separate clinical entity with distinct clinical and molecular characteristics. It is defined by a low level of HER2 protein expression, which distinguishes it from other more aggressive BC subtypes. Early studies suggest that it may have a more favorable prognosis than HER2‐positive BC, as it is less likely to spread to other parts of the body and may be more responsive to standard BC treatments such as chemotherapy, radiation therapy, and hormone therapy. Given the relative new emergence of HER2‐low BC, there is still much to be learned about this subtype; ongoing research is focused on identifying the underlying genetic mutations that contribute to HER2‐low BC as well as developing targeted therapies that can improve outcomes for patients with this disease. This review is aimed at summarizing the current clinical knowledge on HER2‐low BC, with the aim of creating a better understanding of this entity and paving the way for potential interventions and a new standard of care. [ABSTRACT FROM AUTHOR]

Joe Mehanna,1 Fady GH Haddad,1 Roland Eid,1 Matteo Lambertini,2,3 Hampig Raphael Kourie11Oncology Department, Faculty of Medicine, Saint Joseph University of Beirut, Beirut, Lebanon; 2Department of Medical Oncology, U.O.C. Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 3Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, ItalyAbstract: Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy.Keywords: breast cancer, triple-negative, immunotherapy, PARP inhibitors

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. Chromosomal abnormalities are reported to play important roles in CLL pathogenesis and evolution, including deletions of 11q, 13q, 17p, and trisomy12, that are frequently observed and have a known prognostic value. Furthermore, the mutational status of the IGHV gene was reported as an independent prognostic marker in CLL impacting the choice of therapy. We herein, report an unusual presentation of a Lebanese CLL patient with two cytogenetic abnormalities: trisomy 12 and t(14;18)(q32;q21), along with an unmutated IGHV, displaying a favorable response to ibrutinib with a maintained complete remission.

Aim: Report the epidemiologic and histologic characteristics of CNS lesions in the Lebanese population. Methods: We conducted a retrospective study evaluating 2025 CNS lesions diagnosed between 1998 and 2017 in the pathology laboratory of a Lebanese tertiary center. Results: 52.2% of patients were men with a median age of 50 years. The most frequent symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of tumors were primary. Lung (35.6%) and breast (16.5%) were the most frequent primaries of metastases. 46.2% of primary CNS tumors were glial, predominantly astrocytic (56.4%), and (42.5%) were nonglial, predominantly meningeal tumors (58%). Conclusion: Compared with Western literature, the Lebanese population is characterized by a younger age of onset of brain tumors, a lower rate of meningiomas and a higher rate of gliomas.