Expanding Beyond Genetic Subtypes in B-Cell Acute Lymphoblastic Leukemia: A Pathway-Based Stratification of Patients for Precision Oncology.

Precision oncology promises individually tailored drugs and clinical care for patients with cancer: That is, "the right drug, for the right patient, at the right dose, and at the right time." Although stratification of the risk for treatment resistance and toxicity is key to precision oncology, there are multiple ways in which such stratification can be achieved, for example, genetic, functional pathway based, among others. Moving toward precision oncology is sorely needed in the case of acute lymphoblastic leukemia (ALL) wherein adult patients display survival rates ranging from 30% to 70%. The present study reports on the pathway activity signature of adult B-ALL, with an eye to precision oncology. Transcriptome profiles from three different expression datasets, comprising 346 patients who were adolescents or adults with B-ALL, were harnessed to determine the activity of signaling pathways commonly disrupted in B-ALL. Pathway activity analyses revealed that Ph-like ALL closely resembles Ph-positive ALL. Although this was the case at the average pathway activity level, the pathway activity patterns in B-ALL differ from genetic subtypes. Importantly, clustering analysis revealed that five distinct clusters exist in B-ALL patients based on pathway activity, with each cluster displaying a unique pattern of pathway activation. Identifying pathway-based subtypes thus appears to be crucial, considering the inherent heterogeneity among patients with the same genetic subtype. In conclusion, a pathway-based stratification of the B-ALL could potentially allow for simultaneously targeting highly active pathways within each ALL subtype, and thus might open up new avenues of innovation for personalized/precision medicine in this cancer that continues to have poor prognosis in adult patients compared with the children.

Data sharing in cancer research: A qualitative study exploring community members' preferences.

BACKGROUND: Advancements in cancer treatment and survivorship rely on participation in research and access to health records. METHODS: This study explored preferences for data access and sharing in 14 workshops with 42 community members, most of whom were a cancer survivor or carer. Various scenarios for data access and sharing were presented and discussed, with participants' preferences summarized using descriptive statistics. Reasons underlying these preferences were identified through a thematic analysis of workshop transcripts. RESULTS: Most participants indicated a willingness for researchers to use their self-report data and current health records for a specific research project (86%). Many were also willing for their self-report data and current (62%) or all future (44%) health records to be shared with other researchers for use in other studies if made aware of this. Willingness to consent to data access and sharing data in cancer research was influenced by: (i) the potential for data sharing to advance medical discoveries and benefit people impacted by cancer in the future, (ii) transparency around researchers' credibility and their intentions for data sharing, (iii) level of ownership and control over data sharing, and (iv) protocols for privacy and confidentiality in data sharing. CONCLUSIONS: Based on these themes, we present practical strategies for optimizing data access and sharing in cancer research.

An Updated Review of Resistin and Colorectal Cancer.

Resistin is one of the most important adipokines, and its role lies mainly in controlling insulin sensitivity and inflammation. However, over the last years, the study of resistin gained increased popularity since it was proved that there is a considerable relationship between high levels of resistin and obesity as well as obesity-induced diseases, including diabetes, cardiovascular disorders, and cancer. Regarding cancer risk, circulating resistin levels have been correlated with several types of cancer, including colorectal, breast, lung, endometrial, gastroesophageal, prostate, renal, and pancreatic cancer. Colorectal cancer is regarded as a multi-pathway disease. Several pathophysiological features seem to promote colorectal cancer (CRC) such as chronic inflammation, insulin resistance, and obesity. Even though the molecular mechanisms involved in CRC development remain rather vague, it is widely accepted that several biochemical factors promote CRC by releasing augmented pro-inflammatory cytokines, like IGF-I, insulin, sex-steroid hormones, and adipokines. A wide range of research studies has focused on evaluating the impact of circulating resistin levels on CRC risk and determining the efficacy of chemotherapy in CRC patients by measuring resistin levels. Moreover, significant outcomes have emerged regarding the association of specific single nucleotide polymorphisms (SNPs) in the resistin gene and CRC risk. The present study reviewed the role of circulating resistin levels in CRC development and shed light on specific resistin gene SNPs implicated in the disease's development. Finally, we analyzed the impact of resistin levels on the effectiveness of chemotherapy and further discussed whether resistin can be regarded as a valuable biomarker for CRC prognosis and treatment. Resistin is one of the most important adipokines, and its role lies mainly in controlling insulin sensitivity and inflammation. However, over the last years, the study of resistin gained increased popularity since it was proved that there is a considerable relationship between high levels of resistin and obesity as well as obesity-induced diseases, including diabetes, cardiovascular disorders, and cancer. This review discusses the aberrant expression of resistin and its receptors, its diverse downstream signaling, and its impact on tumor growth, metastasis, angiogenesis, and therapy resistance to support its clinical exploitation in biomarker and therapeutic development.

Interpretation of the past, present, and future of organoid technology: an updated bibliometric analysis from 2009 to 2024.

Organoid technology has been developed rapidly in the past decade, which involves the exploration of the mechanism of development, regeneration and various diseases, and intersects among multiple disciplines. Thousands of literature on 3D-culture or organoids have been published in the research areas of cell biology tissue engineering, nanoscience, oncology and so on, resulting in it being challenging for researchers to timely summarize these studies. Bibliometric statistics is a helpful way to help researchers clarify the above issues efficiently and manage the whole landscape systematically. In our study, all original articles on organoids were included in the Web of Science database from January 2009 to May 2024, and related information was collected and analyzed using Excel software, "bibliometrix" packages of the R software, VOSviewer and CiteSpace. As results, a total of 6222 papers were included to classify the status quo of the organoids and predict future research areas. Our findings highlight a growing trend in publications related to organoids, with the United States and Netherlands leading in this field. The University of California System, Harvard University, Utrecht University and Utrecht University Medical Center have emerged as pivotal contributors and the key authors in the field include Clevers, H, Beekman, JM and Spence JR. Our results also revealed that the research hotspots and trends of organoids mainly focused on clinical treatment, drug screening, and the application of materials and technologies such as "hydrogel" and "microfluidic technology" in organoids. Next, we had an in-depth interpretation of the development process of organoid research area, including the emergence of technology, the translation from bench to bedsides, the profiles of the most widely studied types of organoids, the application of materials and technologies, and the emerging organoid-immune co-cultures trends. Furthermore, we also discussed the pitfalls, challenges and prospects of organoid technology. In conclusion, this study provides readers straightforward and convenient access to the organoid research field.

Tackling challenges in rare diseases: The ISGACA approach on non-pancreatic cancers in the periampullary region.

OBJECTIVE: Rare but aggressive cancer types like non-pancreatic periampullary cancers pose unique challenges for cancer research due to their low incidence rates and lack of consensus on optimal treatment strategies, therefore necessitating a collaborative approach. The International Study Group on non-pancreatic peri-Ampullary CAncer (ISGACA) aimed to build a collaborative initiative to pool expertise, funding opportunities, and data from over 60 medical centers, in order to improve outcomes for underrepresented patients with rare cancers. METHODS: The ISGACA approach predefined a stepwise approach including a research scope, establishing a dedicated steering committee, creating a recognizable brand, identifying research gaps, following a well-defined timeline, ensuring robust data collection, addressing legal and ethical considerations, securing financial resources, investing in research ethics training and statistical expertise, raising awareness, creating uniformity, and initiating prospective studies. RESULTS: Overall, 60 medical centers joined the ISGACA consortium (41 in Europe, 15 in North-America, three in Asia, one in Australia). The database includes 4309 patients. Nine publications and several ongoing studies which in turn allowed for a successful application of research grants. Subsequently, an international consensus meeting established uniform definitions and classifications, and one prospective multicenter international clinical trial has been initiated. CONCLUSION: By sharing knowledge, expertise, and clinical data, the ISGACA approach has not only gathered sufficient evidence to secure grants and ethical approvals for prospective studies, but also demonstrates options for standardizing patient care and improving outcomes for patients with rare cancers. The ISGACA approach offers a detailed methodology for initiating research on rare cancers and could serve as a replicable model for future research initiatives.

Metaplastic Breast Carcinoma: A Rare Presentation in a Young Female With Double Hormone Receptor-Positive Tumor.

Metaplastic breast carcinoma (MBC) represents a rare subtype of breast cancer, characterized by poor prognostic indicators that have been recently identified. Clinical and radiological presentations often mimic other breast cancer types, necessitating immunohistochemistry (IHC) for accurate diagnosis. In this study, we report a case involving a 31-year-old female presenting with a painless, fixed, non-inflammatory mass in the left breast, which was confirmed as MBC. Treatment encompassed lumpectomy, chemotherapy, radiotherapy, and subsequent hormonal therapy. Understanding this rarely reported yet aggressive form of breast cancer holds significant importance for clinicians, enabling them to promptly establish a diagnosis and implement effective management strategies.

Factors influencing the research impact in cancer research: a collaboration and knowledge network analysis.

BACKGROUND: Cancer is a major public health challenge globally. However, little is known about the evolution patterns of cancer research communities and the influencing factors of their research capacity and impact, which is affected not only by the social networks established through research collaboration but also by the knowledge networks in which the research projects are embedded. METHODS: The focus of this study was narrowed to a specific topic - 'synthetic lethality' - in cancer research. This field has seen vibrant growth and multidisciplinary collaboration in the past decade. Multi-level collaboration and knowledge networks were established and analysed on the basis of bibliometric data from 'synthetic lethality'-related cancer research papers. Negative binomial regression analysis was further applied to explore how node attributes within these networks, along with other potential factors, affected paper citations, which are widely accepted as proxies for assessing research capacity and impact. RESULTS: Our study revealed that the synthetic lethality-based cancer research field is characterized by a knowledge network with high integration, alongside a collaboration network exhibiting some clustering. We found significant correlations between certain factors and citation counts. Specifically, a leading status within the nation-level international collaboration network and industry involvement were both found to be significantly related to higher citations. In the individual-level collaboration networks, lead authors' degree centrality has an inverted U-shaped relationship with citations, while their structural holes exhibit a positive and significant effect. Within the knowledge network, however, only measures of structural holes have a positive and significant effect on the number of citations. CONCLUSIONS: To enhance cancer research capacity and impact, non-leading countries should take measures to enhance their international collaboration status. For early career researchers, increasing the number of collaborators seems to be more effective. University-industry cooperation should also be encouraged, enhancing the integration of human resources, technology, funding, research platforms and medical resources. Insights gained through this study also provide recommendations to researchers or administrators in designing future research directions from a knowledge network perspective. Focusing on unique issues especially interdisciplinary fields will improve output and influence their research work.

Real-world first-line treatment with pembrolizumab for non-small cell lung carcinoma with high PD-L1 expression: Updated analysis.

BACKGROUND: Selecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum-based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death-ligand 1 (PD-L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD-L1 expression who received MONO or COMB as a first-line treatment. Here, we report updated data and evaluate the long-term outcomes. METHODS: We performed a retrospective multicenter study of 298 patients with NSCLC and high PD-L1 expression who received MONO or COMB as first-line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff. RESULTS: In total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0-1). At the prolonged data cutoff, the median follow-up was 20.2 (range: 0.1-41.4) months. The median progression-free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow-up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO. CONCLUSIONS: COMB may be effective as a first-line treatment for NSCLC with high PD-L1 expression in a selected subset of patients.

Characterisation of Canine and Feline Breast Tumours, Their Metastases, and Corresponding Primary Cell Lines Using LA-REIMS and DESI-MS Imaging.

Breast cancer, a complex disease with a significant prevalence to form metastases, necessitates novel therapeutic strategies to improve treatment outcomes. Here, we present the results of a comparative molecular study of primary breast tumours, their metastases, and the corresponding primary cell lines using Desorption Electrospray Ionisation (DESI) and Laser-Assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) imaging. Our results show that ambient ionisation mass spectrometry technology is suitable for rapid characterisation of samples, providing a lipid- and metabolite-rich spectrum within seconds. Our study demonstrates that the lipidomic fingerprint of the primary tumour is not significantly distinguishable from that of its metastasis, in parallel with the similarity observed between their respective primary cell lines. While significant differences were observed between tumours and the corresponding cell lines, distinct lipidomic signatures and several phospholipids such as PA(36:2), PE(36:1), and PE(P-38:4)/PE(O-38:5) for LA-REIMS imaging and PE(P-38:4)/PE(O-38:5), PS(36:1), and PI(38:4) for DESI-MSI were identified in both tumours and cells. We show that the tumours' characteristics can be found in the corresponding primary cell lines, offering a promising avenue for assessing tumour responsiveness to therapeutic interventions. A comparative analysis by DESI-MSI and LA-REIMS imaging revealed complementary information, demonstrating the utility of LA-REIMS in the molecular imaging of cancer.

Metal-based nanoparticle in cancer treatment: lessons learned and challenges.

Cancer, being one of the deadliest diseases, poses significant challenges despite the existence of traditional treatment approaches. This has led to a growing demand for innovative pharmaceutical agents that specifically target cancer cells for effective treatment. In recent years, the use of metal nanoparticles (NPs) as a promising alternative to conventional therapies has gained prominence in cancer research. Metal NPs exhibit unique properties that hold tremendous potential for various applications in cancer treatment. Studies have demonstrated that certain metals possess inherent or acquired anticancer capabilities through their surfaces. These properties make metal NPs an attractive focus for therapeutic development. In this review, we will investigate the applicability of several distinct classes of metal NPs for tumor targeting in cancer treatment. These classes may include gold, silver, iron oxide, and other metals with unique properties that can be exploited for therapeutic purposes. Additionally, we will provide a comprehensive summary of the risk factors associated with the therapeutic application of metal NPs. Understanding and addressing these factors will be crucial for successful clinical translation and to mitigate any potential challenges or failures in the translation of metal NP-based therapies. By exploring the therapeutic potential of metal NPs and identifying the associated risk factors, this review aims to contribute to the advancement of cancer treatment strategies. The anticipated outcome of this review is to provide valuable insights and pave the way for the advancement of effective and targeted therapies utilizing metal NPs specifically for cancer patients.

Immunohistochemical Detection of Indoleamine 2,3-Dioxygenase in Spontaneous Mammary Carcinomas of 96 Pet Rabbits.

For mammary carcinomas in pet rabbits, prognostic biomarkers are poorly defined, and treatment is limited to surgical excision. Additional treatment options are needed for rabbit patients for which surgery is not a suitable option. In human breast cancer, the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) represents a prognostic biomarker and possible therapeutic target. This retrospective immunohistochemical study examined IDO1 in 96 pet rabbit mammary carcinomas with known mitotic count, hormone receptor status, and percentage of stromal tumor infiltrating lymphocytes (TILs). Tumors were obtained from 96 pet rabbits with an average of 5.5 years. All rabbits with reported sex (n = 88) were female or female-spayed. Of the carcinomas, 94% expressed IDO1, and 86% had sparse TILs consistent with cold tumors. Statistically significant correlations existed between a higher percentage of IDO1-positive tumor cells, lower mitotic counts, and increased estrogen receptor expression. The threshold for significance was IDO1 staining in >10% of tumor cells. These results lead to the assumption that IDO1 expression contributes to tumorigenesis and may represent a prognostic biomarker and possible therapeutic target also in pet rabbit mammary carcinomas. They also support the value of rabbits for breast cancer research.

Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer.

Lung cancer (LC) is a highly invasive malignancy and the leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) as its most prevalent histological subtype. Despite all breakthroughs achieved in drug development, the prognosis of NSCLC remains poor. The mitogen-activated protein kinase signaling cascade (MAPKC) is a complex network of interacting molecules that can drive oncogenesis, cancer progression, and drug resistance when dysregulated. Over the past decades, MAPKC components have been used to design MAPKC inhibitors (MAPKCIs), which have shown varying efficacy in treating NSCLC. Thus, recent studies support the potential clinical use of MAPKCIs, especially in combination with other therapeutic approaches. This article provides an overview of the MAPKC and its inhibitors in the clinical management of NSCLC. It addresses the gaps in the current literature on different combinations of selective inhibitors while suggesting two particular therapy approaches to be researched in NSCLC: parallel and aggregate targeting of the MAPKC. This work also provides suggestions that could serve as a potential guideline to aid future research in MAPKCIs to optimize clinical outcomes in NSCLC.

New perspectives in prognostication of hepatocellular carcinoma: The role and clinical implications of transient receptor potential family genes.

The study titled "Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients" is a significant contribution to hepatocellular carcinoma (HCC) research, highlighting the role of transient receptor potential (TRP) family genes in the disease's progression and prognosis. Utilizing data from The Cancer Genome Atlas database, it establishes a new risk assessment model, emphasizing the interaction of TRP genes with tumor proliferation pathways, key metabolic reactions like retinol metabolism, and the tumor immune microenvironment. Notably, the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes, suggesting its potential as a prognostic biomarker and a target for personalized therapy, particularly in strategies combining immunotherapy and anti-TRP agents.

Incorporating verbal and nonverbal aspects to enhance a model of patient communication in cancer care: A grounded theory study.

PURPOSE: High-quality communication is essential to patient-centered care. Existing communication models and research tends to focus on what is said verbally with little attention to nonverbal aspects of communication. In sensitive and emotionally intensive healthcare encounters, such as in cancer care, provider and patient nonverbal behavior may be particularly important for communicating with empathy. Therefore, the aim of this study was to develop a conceptual model of communication that accounts for nonverbal behavior. METHODS: We followed a systematic grounded theory design that involved semi-structured interviews with 23 providers, including nurse practitioners, physicians, surgeons, and physician's assistants. Using constant comparative analysis, we analyzed transcripts and developed a grounded theory model of communication accounting for nonverbal behavior. RESULTS: The major themes included building rapport, gauging how patients will take bad news, ensuring patients' understanding of their conditions, staying honest but hopeful, centering but guiding patient through cancer care, conveying empathy while managing heightened emotions, and ensuring patient understanding. Throughout the process, providers synthesize both verbal and nonverbal information and apply what they learn to future encounters. CONCLUSIONS: The results extend existing models of patient-centered communication and invite communication intervention and research that incorporates nonverbal behavior. The model contributes an understanding of the full process of communication in clinical encounters.

Cancer research funding in South Asia.

BACKGROUND: The rising burden of cancer significantly influences the global economy and healthcare systems. While local and contextual cancer research is crucial, it is often limited by the availability of funds. In South Asia, with 1.7 million new cancer cases and 1.1 million deaths due to cancer in 2020, understanding cancer research funding trends is pivotal. METHODS: We reviewed funded cancer studies conducted between January 1, 2003, and Dec 31, 2022, using ClinicalTrials.gov, International Cancer Research Partnership (ICRP) Database, NIH World RePORT, and WHO International Clinical Trials Registry Platform (ICTRP). We included funded studies related to all cancer types, conducted in South Asian countries, namely Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. RESULTS: We identified 6561 funded cancer studies from South Asia between 2003 and 2022, increasing from 400 studies in 2003-2007 to 3909 studies in 2018-2022. India had the highest number of funded cancer studies, while Afghanistan, Bhutan, and the Maldives had minimal or no funded cancer research output. Interventional studies (67.3%) were the most common study type funded. The most common cancer sites funded were breast (17.8%), lung (9.9%), oropharyngeal (6.2%), and cervical (5.0%) cancers. On the WHO ICTRP, international funding agencies contributed to a majority of studies (57.5%), except in India where local funding agencies (58.2%) funded more studies. CONCLUSION: This study identified gaps in research funding distribution across cancer types and geographic areas in South Asia. This data can be used to optimize the distribution of cancer research funding in South Asia, fostering equitable advancement in cancer research.

3D Multispheroid Assembly Strategies towards Tissue Engineering and Disease Modeling.

Cell spheroids (esp. organoids) as 3D culture platforms are popular models for representing cell-cell and cell-extracellular matrix (ECM) interactions, bridging the gap between 2D cell cultures and natural tissues. 3D cell models with spatially organized multiple cell types are preferred for gaining comprehensive insights into tissue pathophysiology and constructing in vitro tissues and disease models because of the complexities of natural tissues. In recent years, an assembly strategy using cell spheroids (or organoids) as living building blocks has been developed to construct complex 3D tissue models with spatial organization. Here, a comprehensive overview of recent advances in multispheroid assembly studies is provided. The different mechanisms of the multispheroid assembly techniques, i.e., automated directed assembly, noncontact remote assembly, and programmed self-assembly, are introduced. The processing steps, advantages, and technical limitations of the existing methodologies are summarized. Applications of the multispheroid assembly strategies in disease modeling, drug screening, tissue engineering, and organogenesis are reviewed. Finally, this review concludes by emphasizing persistent issues and future perspectives, encouraging researchers to adopt multispheroid assembly techniques for generating advanced 3D cell models that better resemble real tissues.

Patient, Relative and Staff Experiences of Clinical Trial Participation in Neurooncology: "Maybe You Can Also Show the Positive, No Matter How It Ends".

Purpose: There is a lack of evidence regarding how patients with malignant brain tumor and their relatives experience participation in neurooncological clinical trials. Similarly, insights from the perspective of trial staff caring for this group of patients are missing. This study aims to investigate patient, relative and trial staff experiences regarding participation in clinical neurooncological trials. Methods: Within a qualitative exploratory study, 29 semi-structured interviews with brain tumor patients, relatives and trial staff were conducted and analyzed using reflexive thematic analysis (RTA) by Braun and Clarke. A patient researcher and patient council were involved in data analysis and interpretation. Results: Four themes were developed reflecting significant aspects of the trial experience: 1. "It all revolves around hope"; 2. "Trial participation: experiencing unique medical care"; 3. "Everyone's roles are changing"; 4. "Communication as a possible area of conflict". Experiencing trial participation and general medical treatment were found to be interconnected to such a degree that they were often not meaningfully distinguished by patients and relatives. Conclusion: In addition to assessing traditional endpoints for patient outcomes, we recommend increased emphasis on investigating the impact of the "soft" components constituting trial participation. Due to the interconnectedness of medical treatment and trial participation, we recommend further investigation in comparison to experiences in regular care. A deeper understanding of trial participation is needed to inform improvements for patient experiences and staff satisfaction alongside medical and scientific progress.

The treatment options available to patients with (malignant) brain tumors are currently very limited. Therefore, patients are sometimes offered to participate in a clinical trial. This means that they receive an experimental treatment (eg new medicine) for which it is not yet clear whether it works better than regular medical care. Currently, little is known about how this group of patients, their relatives and the hospital staff who care for them experience the participation in these clinical trials ­ which is what we aimed to explore in our study reported here. Based on interviews with patients, relatives and staff, we found that: trial participation mainly revolves around hope;trial participation entails experiencing unique medical care;trial participation significantly changes the previous roles of patients, relatives and staff;trial participation intensifies communication as a possible area of conflict. By providing information on how patients, relatives and staff make sense of their trial experiences, this study constitutes an important addition to the traditional focus of clinical trials on medical and scientific endpoints (eg progression-free survival). This may help clinicians and researchers involved in cancer research and treatment to understand why "unsuccessful" trials can still be perceived as positive by patients or how hopeful communication may support their patients even when perceived as "unrealistic" from the clinicians' perspective. An in depth understanding of trial participation from the perspective of those affected is needed for improved care experiences alongside medical and scientific progress for cancer treatment.

CRISPR/Cas9-mediated knockout strategies for enhancing immunotherapy in breast cancer.

Breast cancer, a prevalent disease with significant mortality rates, often presents treatment challenges due to its complex genetic makeup. This review explores the potential of combining Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene knockout strategies with immunotherapeutic approaches to enhance breast cancer treatment. The CRISPR/Cas9 system, renowned for its precision in inducing genetic alterations, can target and eliminate specific cancer cells, thereby minimizing off-target effects. Concurrently, immunotherapy, which leverages the immune system's power to combat cancer, has shown promise in treating breast cancer. By integrating these two strategies, we can potentially augment the effectiveness of immunotherapies by knocking out genes that enable cancer cells to evade the immune system. However, safety considerations, such as off-target effects and immune responses, necessitate careful evaluation. Current research endeavors aim to optimize these strategies and ascertain the most effective methods to stimulate the immune response. This review provides novel insights into the integration of CRISPR/Cas9-mediated knockout strategies and immunotherapy, a promising avenue that could revolutionize breast cancer treatment as our understanding of the immune system's interplay with cancer deepens.

Graphene-Based Photodynamic Therapy and Overcoming Cancer Resistance Mechanisms: A Comprehensive Review.

Photodynamic therapy (PDT) is a non-invasive therapy that has made significant progress in treating different diseases, including cancer, by utilizing new nanotechnology products such as graphene and its derivatives. Graphene-based materials have large surface area and photothermal effects thereby making them suitable candidates for PDT or photo-active drug carriers. The remarkable photophysical properties of graphene derivates facilitate the efficient generation of reactive oxygen species (ROS) upon light irradiation, which destroys cancer cells. Surface functionalization of graphene and its materials can also enhance their biocompatibility and anticancer activity. The paper delves into the distinct roles played by graphene-based materials in PDT such as photosensitizers (PS) and drug carriers while at the same time considers how these materials could be used to circumvent cancer resistance. This will provide readers with an extensive discussion of various pathways contributing to PDT inefficiency. Consequently, this comprehensive review underscores the vital roles that graphene and its derivatives may play in emerging PDT strategies for cancer treatment and other medical purposes. With a better comprehension of the current state of research and the existing challenges, the integration of graphene-based materials in PDT holds great promise for developing targeted, effective, and personalized cancer treatments.