Treatment Of Cancer Research Articles

Targeting BTLA with the peptide inhibitor HVEM(14-39) – A new way to restore the activity of T cells in melanoma

The complex of B- and T-lymphocyte attenuator (BTLA) and herpes virus entry mediator (HVEM) plays a critical role in immune regulation and has emerged as a promising therapeutic target for cancer treatment. In this study, we investigated the potential of the peptide inhibitor HVEM(14-39) to restore peripheral T cell activity in patients with advanced melanoma. In these patients, CD8+ T cells downregulated BTLA expression and increased HVEM expression upon activation. The addition of HVEM(14-39) reduced the percentage of BTLA+ CD8+ T cells and increased the subpopulation of HVEM+ CD8+ T cells. Additionally, HVEM(14-39) enhanced T cell activation, proliferation, and the shift toward effector memory T cell subpopulations. Finally, this peptide affected the proliferation rate and late apoptosis of melanoma cell line in co-culture with T cells. These findings suggest that HVEM(14-39) can overcome T cell exhaustion and improve antitumor responses. Peptide-based immunotherapy targeting the BTLA-HVEM complex offers a promising alternative to monoclonal antibody-based therapies, with the potential for fewer side effects and higher treatment efficacy.

Novel 2-pyridone Analogs with Anti-cancer Activity: Synthesis, In silico, and In vitro Evaluation

Background: 2-pyridone is frequently used to synthesize and develop new bioactive molecules approved for treating many diseases. The produced compounds play a significant role in inhibiting cancer growth. Objectives: Through a molecular docking investigation, we determined the binding affinity of 2-pyridone compounds with the Matrix Metalloproteinase receptor, which allowed us to develop, produce, and test the in vitro anticancer efficacy of those compounds. Method: 2-pyridones (A1-A12) were synthesized in a multistep process, followed by spectrum analysis to confirm the structure. In silico screening of the synthesized compounds was carried out with the assistance of AutoDock software. Flow cytometry was used on the HT-29 colon cancer cell line to measure A1-A12’s anticancer effect in a lab setting. Results: The enzyme matrix metalloproteinase receptor and A1-A12 interacted unexpectedly during a docking study (MMP3, MMP9 & MMP13). Research has shown a strong affinity for MMP3 receptors for A9, A10, A11, A12, and A4, respectively. Further flow cytometric testing revealed compound A9 (R1) to be highly cytotoxic, with an IC50 value of 20.77 M. The anticancer activity of A9 (R1) against HT-29 colon cancer cell lines was also confirmed by in vitro results. Conclusion: These findings suggested that 2-pyridone compounds have promising therapeutic potential for cancer treatment, and more research on these lead moieties would be advantageous to discovering an effective anticancer drug.

Prediction of Abnormal Growth of Breast Cancer Cell Using Support Vector Machine

Abstract: Breast cancer is a serious health concern that affects millions of women worldwide. Early detection of breast cancer is crucial for effective treatment and improved survival rates. Artificial intelligence (AI) has shown great promise in the field of medical imaging and has been increasingly used for breast cancer detection. Cancer is one of the most dangerous diseases to humans, and yet no permanent cure has been developed for it. Breast cancer is one of the most common cancer types. According to the National Breast Cancer foundation, in 2020 alone, more than 276,000 new cases of invasive breast cancer and more than 48,000 non-invasive cases were diagnosed in the US. To put these figures in perspective, 64% of these cases are diagnosed early in the disease’s cycle, giving patients a 99% chance of survival. In this paper we develop a system for diagnosis, prognosis and prediction of breast cancer using AI. This will assist the doctors in diagnosis of the disease. In this research work, we systematically reviewed previous work done on detection and treatment of breast cancer using genetic sequencing or histopathological imaging with the help of deep learning and machine learning We use of AI for breast cancer detection, including studies that have used mammography, ultrasound, and magnetic resonance imaging (MRI) as imaging modalities. AI can also improve the accuracy and efficiency of breast cancer screening and diagnosis, as well as the challenges that must be addressed to ensure the successful integration of AI into clinical practice. However, further research and development are needed to optimize AI algorithms and ensure their safety and effectiveness in clinical practice. Breast cancer detection has emerged as a critical area of research, leveraging the power of Artificial Intelligence (AI) to enhance diagnostic accuracy and efficiency. Utilizing AI technologies, particularly deep learning, enables the development of robust and precise models for early breast cancer detection. These models analyze mammographic images, identifying subtle patterns indicative of malignancies that may escape human eye detection. Transfer learning, employing pre-trained neural network architectures, has demonstrated significant success in leveraging existing knowledge for improved performance. The integration of convolutional neural networks (CNNs) and image processing techniques empowers AI models to discern subtle abnormalities, aiding in the timely identification of potential breast tumors. Additionally, AI-driven diagnostic tools can streamline radiologists' workflow, providing rapid and reliable assessments, ultimately contributing to early intervention and improved patient outcomes. As these technologies continue to evolve, the synergy between AI and breast cancer detection promises to revolutionize screening methods, fostering a paradigm shift towards more accurate, efficient, and accessible diagnostic practices in the realm of breast health.

Screening and molecular identification of l-asparaginase producing bacteria with ansB gene from sewage water

Enzymes are vital biocatalysts facilitating biochemical reactions in organisms, playing pivotal roles in both biological systems and numerous industrial applications. This study focuses on the isolation and screening of asparaginase-producing bacteria from sewage water samples in Bhopal City. A modified M9 media, supplemented with asparagine and phenol red, was used to isolate asparaginase-producing bacteria. Out of the ten samples, seven exhibited asparaginase activity. Two bacterial strains, identified as Bacillus tropicus (S-1) and Priestiaveravalensis (S-2), were found to harbor the ansB gene. Sequence analysis revealed a 96.52% and 95.09% resemblance to Bacillus tropicus MCCC 1A01406 and Priestiaveravalensis strain SGD-V-76, respectively. These findings highlight the potential of these bacterial strains in producing L-asparaginase, emphasizing their significance in pharmaceutical applications, particularly in cancer treatment.

Pharmacological and Biochemical activities of plantago major L

Throughout human history, natural remedies have been sought to treat diseases. The therapeutic wounds of plants are accepted worldwide as a result of many studies and research. Medicinal plants have started to be used in the pharmaceutical sector due to the chemical compounds contained in their structures. One of the potential plants that can be used in traditional medicine is the broadleaf plantain, white man's footprint, waybread, or greater plantain. Scientifically known as Plantago major, it is a wild plant belonging to the Plantaginaceae family that can reach a height of about 15 cm. Plantago major leaves have been used for centuries almost everywhere in the world as a wound healer and in the treatment of many diseases other than wound healing. Among them are treatments for skin, respiratory organs, digestive organs, reproduction, circulatory diseases, infections, and cancer. It is also used as a decongestant and analgesic. Plantago major contains biologically active compounds such as polysaccharides, lipids, caffeic acid derivatives, flavonoids, iridoid glycosides, and terpenoids. Alkaloids and some organic acids have also been detected. There are several biological activities from plant extracts, including wound healing activity, anti-inflammatory, analgesic, antioxidant, weak antibiotic, immune modulating, and antiulcerogenic activity. The widespread use of Plantago species in food and traditional medicine has attracted the attention of researchers looking for active principles and mechanisms of action. However, more studies are needed to better prove the medical applications, phytochemical properties, and pharmacological properties of this breed.

Artificial intelligence and machine learning for early cancer prediction and response

Worldwide, cancer claims more lives than any other disease. Although cancer detection, prognosis, and treatment have all advanced, one major obstacle is the lack of personalized, data-driven care. Artificial intelligence (AI), used to forecast and automate numerous malignancies, has emerged as a viable solution for increasing healthcare accuracy and patient outcomes. Artificial intelligence applications in cancer include risk evaluation, early detection, patient prognosis prediction, and treatment selection based on comprehensive data. Machine learning (ML), a form of artificial intelligence that allows computers to learn from training data, is very successful in predicting breast, brain, lung, liver, and prostate cancers. Indeed, AI and machine learning have outperformed physicians in predicting cancer. These technologies can potentially enhance the diagnosis, prediction, and quality of life of patients with a wide range of disorders, not just cancer. As a result, it is critical to enhance existing AI and ML technologies and create new programs to help patients. This article discusses the use of AI and machine learning algorithms in cancer prediction, including its present uses, future possibilities, and limitations.

Exploring Quinoxalinone Derivatives as Promising Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors for Cancer Therapy

E GFR plays an extensive role in the signaling pathway such as proliferation, migration, invasion. However, the malfunctioning of the epidermal growth factor receptor (EGFR) is a crucial factor in cancer progression. The search for new kinase inhibitors is necessary due to the evolving nature of diseases and the emergence of resistant strains, prompting the need for novel compounds that can effectively target and inhibit specific kinases for therapeutic purposes. This study explores quinoxalinone derivatives, comprised of benzene and pyrazine aromatic rings, as novel potential EGFR kinase inhibitors for cancer therapy, fulfilling an essential need in targeted cancer treatments. We utilized molecular docking to examine 46 synthesized quinoxalinone derivatives for their interaction with the tyrosine kinase domain of EGFR. Fifteen compounds exhibited strong binding affinities. Notably, LS3c, MN333, and MN343 displayed significant inhibitory effects on A431 cells with half-maximum inhibitory concentration (IC50) values comparable to gefitinib, erlotinib, and afatinib in enzymatic kinase assays. Subsequent experiments revealed that LS3c and MN343 effectively inhibit EGFR-expressing cell lines with low hepatotoxicity. MN343, the most potent compound, was selected for molecular dynamic simulation to understand its interaction with the tyrosine kinase of EGFR. To investigate the interaction between MN343 and EGFR’s tyrosine kinase, MM-PBSA analysis identified key residues (L694, V702, L768, M769, and L820) crucial for interaction, highlighting the potential of MN343 as a clinical EGFR tyrosine kinase inhibitor. The need for discovering new kinase inhibitors arises from the dynamic nature of diseases and the appearance of resistant strains, emphasizing the requirement for innovative compounds capable of targeting and inhibiting specific kinases effectively for therapeutic applications.

Interpretation of the surgical treatment of pancreatic cancer of the 2024 edition of the NCCN guidelines

Pancreatic cancer is a highly malignant tumor in the digestive system, and radical surgery is the only possible means to cure pancreatic cancer at present. In the past decade, pancreatic surgery has been developing rapidly, with various new technologies and concepts emerging, among which the use of minimally invasive techniques and the popularization of neoadjuvant therapy concepts are the most notable. At the same time, the surgical treatment of pancreatic cancer still has a long way to go, and many problems need to be solved urgently. This article introduces the surgical treatment of pancreatic cancer in the 2024 edition of the NCCN guidelines, focusing on minimally invasive and open surgical treatments, expanded lymph node dissection, combined vascular resection and reconstruction, surgical treatment of pancreatic neck cancer and neoadjuvant therapy, and briefly discussing the unresolved issues.

Oocyte collection and outcome following oncologic treatment: a retrospective multicentre study

PurposeThis study assesses fertility treatment outcomes in female patients who had undergone successful oocyte retrieval following cancer therapy.MethodsBetween January 2020 and December 2022, we collected fertility treatment data from six participating centres in Spain and Germany. All patients associated with this data had undergone successful oocyte retrieval following cancer treatment.ResultsWomen had most frequently been diagnosed with a haematological (41.9%), breast (22.6%) or gynaecological malignancy (12.9%); two thirds (67.7%) had previously received a chemotherapy, half a radiotherapy (53.3%) and 45.2% had undergone surgery. On average, 7 years (range 0–28) had passed between cancer treatment and first ovarian stimulation cycle. Forty-nine ovarian stimulation cycles had been conducted on these 31 women between 2004 and 2021 (mean age at first oocyte collection following treatment: 34.8 ± 5.7 years). On average, 7 oocytes were collected per cycle (range 0–26) and 11 were collected per patient (range 0–51). Out of the 190 oocytes collected for immediate use of artificial reproductive technique, 139 were fertilised at a rate of 73%. Live birth rate per fresh transfer was 45% (9/20); no births were reported following cryotransfer (0/10). Mean values of anti-Mullerian hormone (AMH) before stimulation declined with time since treatment; however, oocytes were successfully collected from four women with an AMH of <0.5 ng/ml, although no pregnancies were reported. Ten pregnancies were documented; 3 ended in miscarriage. Two twin and 5 single pregnancies resulted in nine live births. On average, children were carried to term.ConclusionIn this small cohort, oocytes were successfully collected after chemotherapy and radiotherapy, despite—in individual cases—low AMH values. Further studies are needed to enrich the database and ultimately provide appropriate counselling to female cancer patients regarding expectations and ART outcome following cancer therapy.

Mechanistic analyses reveal that Pueraria montana var. lobata (Willd.) is effective in inhibiting ovarian cancer progression.

Ovarian cancer (OC) is a common malignancies of the female genitalia. P. montana var. lobata (Willd.), a herb with anti-tumor effects, is widely used in the clinical treatment of ovarian cancer (OC), but the ingredients and molecular mechanism of action remains to be explored. In this study, we extracted the main active ingredients of P. montana var. lobata (Willd.) from the TCMSP database, and predicted its potential targets of action against OC from the DisGeNET and GeneCards databases. Protein-protein interaction (PPI) was constructed using the STRING database, while pathway enrichment analyses were performed using the DAVID database. Next, we generated an Ingredient-Target-Pathway network using Cytoscape 3.7.2, then processed the key targets of action and main active ingredients for molecular docking.The results showed that seven active ingredients of P montana var. lobata (Willd.) were associated with treating for OC, namely beta-sitosterol, coumestrol, daidzein, formononetin, genistein, puerarin and scoparone, two important targets Casp3 and Jun, and signaling pathways of P. montana var. lobata (Willd.) against the progression of OC. TUNEL staining, enzyme-linked immunosorbent assay (ELISA), and Western blot assays, the pharmacodynamic effect of puerarin in the treatment of OC and the major targets were verified. Animal experiment demonstrated that application of puerarin at different times of modeling not only upregulated expression of Casp3, Smac, and c-jun proteins, but also promoted apoptosis in tumor cells, hence inhibiting progression of OC. This study demonstrates that P. montana var. lobata (Willd.) can thereby induce apoptosis in tumor cells and inhibit malignant progression through activating expression of Casp3, smac, and c-jun proteins to regulate related apoptosis pathways, as validated by network pharmacology predictions and animal experiments, and can be verifed by large-scale clinical trials in the future. This study also provides theoretical support and new research perspectives for this disease.

Update - Stage-dependent standards and innovations in the treatment of colorectal cancer

Update - Stage-dependent standards and innovations in the treatment of colorectal cancer

FDA Approval Summary: Fruquintinib for the Treatment of Refractory Metastatic Colorectal Cancer.

On November 8, 2023, the FDA approved fruquintinib, an inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3, for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy, an anti‑VEGF therapy, and, if RAS wild‑type and medically appropriate, an anti EGFR therapy. Approval was based on Study FRESCO-2, a globally-conducted, double-blind, placebo-controlled randomized trial. The primary endpoint was overall survival (OS). The key secondary endpoint was progression-free survival (PFS). A total of 691 patients were randomized (461 and 230 into the fruquintinib and placebo arms, respectively). Fruquintinib provided a statistically significant improvement in OS with a hazard ratio (HR) of 0.66 (95% CI: 0.55, 0.80; p<0.001). The median OS was 7.4 months (95% CI: 6.7, 8.2) in the fruquintinib arm and 4.8 months (95% CI: 4.0, 5.8) for the placebo arm. Adverse events observed were generally consistent with the known safety profile associated with inhibition of the VEGFR. The results of FRESCO-2 were supported by the FRESCO study, a double-blind, single country, placebo-controlled, randomized trial in patients with refractory mCRC who have been previously treated with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy. In FRESCO, the OS HR was 0.65 (95% CI: 0.51, 0.83; p<0.001). FDA concluded that the totality of the evidence from FRESCO-2 and FRESCO supported an indication for patients with mCRC with prior treatment with fluoropyrimidine, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild‑type and medically appropriate, an anti-EGFR therapy.

Electrochemical Characterization of the Encapsulation and Release of 5-Fluorouracil in Nanocarriers Formed from Soy Lecithin Vesicles.

5-Fluorouracil (5-FU) is an antineoplastic agent known for its low bioavailability and limited cellular penetration, often resulting in adverse effects on healthy cells. Thus, finding vehicles that enhance bioavailability, enable controlled release, and mitigate adverse effects is crucial. The study focuses on encapsulating 5-FU within soy lecithin vesicles (SLVs) and assessing its impact on the carrier's properties and functionality. Results show that incorporating 5-FU does not affect SLVs' size or polydispersity, even postlyophilization. Liberation of 5-FU from SLVs requires system disruption rather than spontaneous release, with an encapsulation efficiency of approximately 43% determined using Square Wave Voltammetry. Cytotoxicity assays on colorectal cancer cells reveal SLV-based delivery's significant efficacy, surpassing free drug solution effects with 45% cell viability after 72 h vs 73% viability. The research addresses 5-FU's limited bioavailability by creating a biocompatible nanocarrier for efficient drug delivery, highlighting SLVs as promising for targeted cancer therapy due to sustained antiproliferative effects and improved cellular uptake. The study underscores the importance of tailored drug delivery systems in enhancing therapeutic outcomes and suggests SLV/5-FU formulations as a potential advancement in cancer treatment strategies.

Identifying Potential SOS1 Inhibitors via Virtual Screening of Multiple Small Molecule Libraries against KRAS-SOS1 Interaction.

The RAS-MAPK signaling pathway, crucial for cell proliferation and differentiation, involves key proteins KRAS and SOS1. Mutations in the KRAS and SOS1 genes are implicated in various cancer types, including pancreatic, lung, and juvenile myelomonocytic leukemia. There is considerable interest in identifying inhibitors targeting KRAS and SOS1 to explore potential therapeutic strategies for cancer treatment. In this study, advanced in silico techniques were employed to screen small molecule libraries at this interface, leading to the identification of promising lead compounds as potential SOS1 inhibitors. Comparative analysis of the average binding free energies of these predicted potent compounds with known SOS1 small molecule inhibitors revealed that the identified compounds display similar or even superior predicted binding affinities compared to the known inhibitors. These findings offer valuable insights into the potential of these compounds as candidates for further development as effective anti-cancer agents.

A fresh perspective on advances in pancreatic cancer treatment over the past two decades

In the past two decades, significant advances have been made in the treatment of pancreatic cancer.Numerous first-line treatments, such as gemcitabine combined with erlotinib, gemcitabine combined with albumin-bound paclitaxel, FOLFIRINOX, and NALIRIFOX, have emerged;surgery-centered treatment has gradually become the mains clinical strategy.However, behind these achievements, the new drugs developed with substantial funding have not extended the median survival time of patients with advanced pancreatic cancer to more than one year; the 5-year survival rate for postoperative patients remains below 30%. While harboring hope and being proactive, researchers must also soberly reflect and continually reassess our direction, in anticipation of bringing tangible clinical benefits to pancreatic cancer patients at an early date.

Does structural racism impact receipt of NCCN guideline-concordant breast cancer treatment?

Disparities in breast cancer survival remain a challenge. We aimed to analyze the effect of structural racism, as measured by the Index of Concentration at the Extremes (ICE), on receipt of National Cancer Center Network (NCCN) guideline-concordant breast cancer treatment. We identified patients treated at two institutions from 2005 to 2017 with stage I-IV breast cancer. Census tracts served as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed to create 5 models, controlling for economic segregation, non-Hispanic Black (NHB) segregation, NHB/economic segregation, Hispanic segregation, and Hispanic/economic segregation. Multi-level logistic regression models were used to determine the association between individual and neighborhood-level characteristics on receipt of NCCN guideline-concordant breast cancer treatment. 5173 patients were included: 55.2% were Hispanic, 27.5% were NHW, and 17.3% were NHB. Regardless of economic or residential segregation, a NHB patient was less likely to receive appropriate treatment [(OR)Model1 0.58 (0.45-0.74); ORModel2 0.59 (0.46-0.78); ORModel3 0.62 (0.47-0.81); ORModel4 0.53 (0.40-0.69); ORModel5 0.59(0.46-0.76); p < 0.05]. To our knowledge, this is the first analysis assessing receipt of NCCN guideline-concordant treatment by ICE, a validated measure for structural racism. While much literature emphasizes neighborhood-level barriers to treatment, our results demonstrate that compared to NHW patients, NHB patients are less likely to receive NCCN guideline-concordant breast cancer treatment, independent of economic or residential segregation. Our study suggests that there are potential unaccounted individual or neighborhood barriers to receipt of appropriate care that go beyond economic or residential segregation.

Barriers to cancer treatment for people experiencing socioeconomic disadvantage in high-income countries: a scoping review

BackgroundDespite advances in cancer research and treatment, the burden of cancer is not evenly distributed. People experiencing socioeconomic disadvantage have higher rates of cancer, later stage at diagnoses, and are dying of cancers that are preventable and screen-detectable. However, less is known about barriers to accessing cancer treatment.MethodsWe conducted a scoping review of studies examining barriers to accessing cancer treatment for populations experiencing socioeconomic disadvantage in high-income countries, searched across four biomedical databases. Studies published in English between 2008 and 2021 in high-income countries, as defined by the World Bank, and reporting on barriers to cancer treatment were included.ResultsA total of 20 studies were identified. Most (n = 16) reported data from the United States, and the remaining included publications were from Canada (n = 1), Ireland (n = 1), United Kingdom (n = 1), and a scoping review (n = 1). The majority of studies (n = 9) focused on barriers to breast cancer treatment. The most common barriers included: inadequate insurance and financial constraints (n = 16); unstable housing (n = 5); geographical distribution of services and transportation challenges (n = 4); limited resources for social care needs (n = 7); communication challenges (n = 9); system disintegration (n = 5); implicit bias (n = 4); advanced diagnosis and comorbidities (n = 8); psychosocial dimensions and contexts (n = 6); and limited social support networks (n = 3). The compounding effect of multiple barriers exacerbated poor access to cancer treatment, with relevance across many social locations.ConclusionThis review highlights barriers to cancer treatment across multiple levels, and underscores the importance of identifying patients at risk for socioeconomic disadvantage to improve access to treatment and cancer outcomes. Findings provide an understanding of barriers that can inform future, equity-oriented policy, practice, and service innovation.

Emotional Repercussions of Grandparents Facing the Illness and Treatment of Cancer in Pediatric Oncology at a Reference Hospital.

Childhood cancer, especially leukemias and central nervous system tumors, deeply impacts families, requiring important decisions during treatment. Parents, overwhelmed with increasing responsibilities, can rely on the crucial support of grandparents, both in providing significant emotional support and in actively participating in caring for their grandchildren, even if it affects their own daily activities and quality of life. Therefore, we sought to analyze the emotional repercussions of grandparents facing the illness and treatment of cancer. It was based on a qualitative cross-sectional study conducted at a reference hospital of the Unified Health System (SUS) in Pernambuco, Brazil, from December 2023 to February 2024. Data collection was performed through semi-structured and audio-recorded interviews, with participants' consent, transcribed in full, and analyzed using the Bardin technique. Five grandmothers participated in the study, all of them female, aged 52 to 68 years, with a mean age of 61.2 years. The study highlights the importance of grandparents in caring for their grandchildren, emphasizing the emotional challenges present in diagnosis and treatment.

Imidazole[1,5-a]pyridine derivatives as EGFR tyrosine kinase inhibitors unraveled by umbrella sampling and steered molecular dynamics simulations

Although the use of the tyrosine kinase inhibitors (TKIs) has been proved that it can save live in a cancer treatment, the currently used drugs bring in many undesirable side-effects. Therefore, the search for new drugs and an evaluation of their efficiency are intensively carried out. Recently, a series of eighteen imidazole[1,5-a]pyridine derivatives were synthetized by us, and preliminary analyses pointed out their potential to be an important platform for pharmaceutical development owing to their promising actions as anticancer agents and enzyme (kinase, HIV-protease,…) inhibitors. In the present theoretical study, we further analyzed their efficiency in using a realistic scenario of computational drug design. Our protocol has been developed to not only observe the atomistic interaction between the EGFR protein and our 18 novel compounds using both umbrella sampling and steered molecular dynamics simulations, but also determine their absolute binding free energies. Calculated properties of the 18 novel compounds were in detail compared with those of two known drugs, erlotinib and osimertinib, currently used in cancer treatment. Inspiringly the simulation results promote three imidazole[1,5-a]pyridine derivatives as promising inhibitors into a further step of clinical trials.

The role of PD-1/PD-L1 signaling pathway in cancer pathogenesis and treatment: a systematic review

Aim: Cancer as a complex disease poses significant challenges for both diagnosis and treatment. Researchers have been exploring various avenues to find effective therapeutic strategies, with a particular emphasis on cellular signaling pathways and immunotherapy. One such pathway that has recently been suggested is the PD-1/PD-L1 pathway, which is an immune checkpoint signaling system that plays an important role in regulating the immune system and maintaining tissue homeostasis. Cancer cells exploit this pathway by producing PD-L1, which attaches to PD-1 on T cells, thus inhibiting immune responses and enabling the cancer cells to escape detection by the immune system. This study aimed to evaluate the role of the PD-1/PD-L1 pathway in cancer pathogenesis and treatment. Method: This study was performed based on the principles of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). All in vitro , in vivo , and clinical studies that were published in English have been considered during a thorough search of the Scopus, Web of Science, and PubMed databases without date restriction until March 2024. Results: According to the studies reviewed, the PD-1/PD-L1 signaling axis suggests promising therapeutic effects on various types of cancers such as non-small cell lung cancer, melanoma, breast cancer, hepatocellular carcinoma, squamous cell carcinoma, and colorectal cancer, among others. Additionally, research suggests that immune checkpoint inhibitors that block PD1/PD-L1, such as pembrolizumab, atezolizumab, nivolumab, durvalumab, cemiplimab, avelumab, etc. , can effectively prevent tumor cells from escaping the immune system. Moreover, there might be a possible interaction between microbiome, obesity, etc. on immune mechanisms and on the immune checkpoint inhibitors (ICIs). Conclusion: Although we have gained considerable knowledge about ICIs, we are still facing challenges in effectively prescribing the appropriate ICIs for individual patients. This is largely due to the complex interactions between different intracellular pathways, which need to be thoroughly studied. To resolve this issue, it is necessary to conduct more reliable clinical trials that can produce a scientific consensus.