Showing papers on "Cancer research published in 2023"

Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated <i>BRAF</i>-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial

Abstract: PURPOSE Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for BRAFV600-mutant metastatic melanoma. METHODS SECOMBIT is a randomized, three-arm, noncomparative phase II trial (ClinicalTrials.gov identifier: NCT02631447 ). Patients with untreated, metastatic BRAFV600-mutant melanoma from 37 sites in nine countries were randomly assigned to arm A (encorafenib [450 mg orally once daily] plus binimetinib [45 mg orally twice daily] until progressive disease [PD] -> ipilimumab plus nivolumab [ipilimumab 3 mg/kg once every 3 weeks and nivolumab 1 mg/kg once every 3 weeks × four cycles -> nivolumab 3 mg/kg every 2 weeks]), arm B [ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib], or arm C (encorafenib plus binimetinib for 8 weeks -> ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib). The primary end point was overall survival (OS) at 2 years. Secondary end points included total progression-free survival, 3-year OS, best overall response rate, duration of response, and biomarkers in the intent-to-treat population. Safety was analyzed throughout sequential treatment in all participants who received at least one dose of study medication. RESULTS A total of 209 patients were randomly assigned (69 in arm A, 71 in arm B, and 69 in arm C). At a median follow-up of 32.2 (interquartile range, 27.9-41.6) months, median OS was not reached in any arm and more than 30 patients were alive in all arms. Assuming a null hypothesis of median OS of ≤ 15 months, the OS end point was met for all arms. The 2-year and 3-year OS rates were 65% (95% CI, 54 to 76) and 54% (95% CI, 41 to 67) in arm A, 73% (95% CI, 62 to 84) and 62% (95% CI, 48 to 76) in arm B, and 69% (95% CI, 59 to 80) and 60% (95% CI, 58 to 72) in arm C. No new safety signals emerged. CONCLUSION Sequential immunotherapy and targeted therapy provide clinically meaningful survival benefits for patients with BRAFV600-mutant melanoma.

Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma

Abstract: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. Download a PDF of the Research Summary. In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant–adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. At a median follow-up of 14.7 months, the neoadjuvant–adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P=0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant–adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant–adjuvant group and 14% in the adjuvant-only group. Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.) QUICK TAKE VIDEO SUMMARYNeoadjuvant Pembrolizumab for Advanced Melanoma 02:13

Significance of miRNAs on the thyroid cancer progression and resistance to treatment with special attention to the role of cross-talk between signaling pathways.

Abstract: Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. It has many types, the Papillary thyroid cancer (PTC)(most common and follicular thyroid carcinoma (FTC). Several risk factors have been associated with TC radiation exposure, autoimmunity, and genetics. Microribonucleic acids (miRNAs) are the most important genetic determinants of TC. They are small chains of nucleic acids that are able to inhibit the expression of several target genes. They could target several genes involved in TC proliferation, angiogenesis, apoptosis, development, and even resistance to therapy. Besides, they could influence the stemness of TC. Moreover, they could regulate several signaling pathways such as WNT/β-catenin, PI3K/AKT/mTOR axis, JAK/STAT, TGF- β, EGFR, and P53. Besides signaling pathways, miRNAs are also involved in the resistance of TC to major treatments such as surgery, thyroid hormone-inhibiting therapy, radioactive iodine, and adjuvant radiation. The stability and sensitivity of several miRNAs might be exploited as an approach for the usage of miRNAs as diagnostic and/or prognostic tools in TC.

miRNAs as cornerstones in chronic lymphocytic leukemia pathogenesis and therapeutic resistance- An emphasis on the interaction of signaling pathways.

Abstract: Chronic lymphocytic leukemia (CLL) accounts for the vast majority of cases of leukemia. Patients of advanced age are more likely to develop the condition, which has a highly varied clinical course. Consideration of illness features and preceding treatment sequence, as well as patient preferences and comorbidities, is necessary for selecting the appropriate treatment for the appropriate patient. Therefore, there is an urgent need for novel biomarkers with high sensitivity and specificity to detect CLL early, monitor CLL patients, select the treatment responders, and reduce ineffective treatment, unwanted side effects, and unnecessary expenses. In both homeostasis and illness, microRNAs (miRNAs/miRs) play a vital role as master regulators of gene expression and, by extension, protein expression. MiRNAs typically reduce the stability of mRNAs, including those encoding genes involved in tumorigenesis processes as cell cycle regulation, inflammation, stress response, angiogenesis, differentiation, apoptosis, and invasion. Due to their unique properties, miRNAs are rapidly being exploited as accurate biomarkers for illness detection, and medicines based on miRNA targets are finding widespread application in clinical practice. Accordingly, the current review serves as a quick primer on CLL and the biogenesis of miRNAs. In addition to providing a brief overview of the miRNAs whose function in the progression of CLL has been established by recent in vitro or in vivo research through articulating the influence of these miRNAs on a wide variety of cellular functions, including increased proliferative potential; support for angiogenesis; cell cycle aberration; evasion of apoptosis; promotion of metastasis; and reduced sensitivity to specific treatments.

The role of miRNAs in the pathogenesis and therapeutic resistance of endometrial cancer: a spotlight on the convergence of signaling pathways.

Abstract: Endometrial cancer (EC) is the 2nd common cancer in females after breast cancer. Besides, it's the most common among gynecological cancers. Several epigenetic factors such as miRNAs have been reported to affect EC aspects including initiation, progression, angiogenesis, and resistance to therapy. miRNAs could regulate the expression of various genes involved in EC pathogenesis. This effect is attributed to miRNAs' effects in proliferation, apoptosis, cell cycle, angiogenesis, invasion, and metastasis. miRNAs also influence crucial EC-related mechanistic pathways such as JAK/STAT axis, EGFR, TGF-β signaling, and P53. Beside pathogenesis, miRNAs also have the potential to affect EC response to treatments including radio and chemotherapy. Thus, this review aims to illustrate the link between miRNAs and EC; focusing on the effects of miRNAs on EC signaling pathways.

Single-cell spatial immune landscapes of primary and metastatic brain tumours

Abstract: Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues3. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.

Neoantigens: promising targets for cancer therapy

Abstract: Abstract Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma

Abstract: PURPOSE The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma. METHODS Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 10 6 plaque-forming unit (PFU) followed by ≤ 4 × 10 8 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis. RESULTS Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm. CONCLUSION T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.

miRNAs as potential game-changers in melanoma: A comprehensive review.

Abstract: Melanoma is the sixth most frequent malignancy. It represents 1.7% of all cancer cases worldwide. Many risk factors are associated with melanoma including ultraviolet radiation skin phenotype, Pigmented Nevi, Pesticides, and genetic and epigenetic factors. Of the main epigenetic factors affecting melanoma are microribonucleic acids (miRNAs). They are short nucleic acid chains that have the potential to prevent the expression of a number of target genes. They could target a number of genes related to melanoma initiation, stemness, angiogenesis, apoptosis, proliferation, and potential resistance to treatment. Additionally, they can control several melanoma signaling pathways, including P53, WNT/-catenin, JAK/STAT, PI3K/AKT/mTOR axis, TGF- β, and EGFR. MiRNAs also play a role in the resistance of melanoma to essential treatment regimens. The stability and abundance of miRNAs might be important factors enhancing the use of miRNAs as markers of prognosis, diagnosis, stemness, survival, and metastasis in melanoma patients.

miRNAs role in cervical cancer pathogenesis and targeted therapy: Signaling pathways interplay.

Abstract: Cervical cancer (CC) is the primary cause of cancer deaths in underdeveloped countries. The persistence of infection with high-risk human papillomavirus (HPV) is a significant contributor to the development of CC. However, few women with morphologic HPV infection develop invasive illnesses, suggesting other mechanisms contribute to cervical carcinogenesis. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. They had the power to regulate CC's invasion, pathophysiology, angiogenesis, apoptosis, proliferation, and cell cycle phases. Further research is required, even though novel methods have been developed for employing miRNAs in the diagnosis, and treatment of CC. We'll go through some of the new findings about miRNAs and their function in CC below. The function of miRNAs in the development of CC and its treatment is one of these. Clinical uses of miRNAs in the analysis, prediction, and management of CC are also covered.

Targeting the NRF2/KEAP1 pathway in cervical and endometrial cancers.

Abstract: Cervical and endometrial cancers are among the most dangerous gynaecological malignancies, with high fatality and recurrence rates due to frequent diagnosis at an advanced stage and chemoresistance onset. The NRF2/KEAP1 signalling pathway plays an important role in protecting cells against oxidative damage due to increased reactive oxygen species (ROS) levels. NRF2, activated by ROS, induces the expression of antioxidant enzymes such as heme oxygenase, catalase, glutathione peroxidase and superoxide dismutase which neutralize ROS, protecting cells against oxidative stress damage. However, activation of NRF2/KEAP1 signalling in cancer cells results in chemoresistance, inactivating drug-mediated oxidative stress and protecting cancer cells from drug-induced cell death. We review the literature on the role of the NRF2/KEAP1 pathway in cervical and endometrial cancers, with a focus on the expression of its components and downstream genes. We also examine the role of the NRF2/KEAP1 pathway in chemotherapy resistance and how this pathway can be modulated by natural and synthetic modulators.

γδ T cells are effectors of immunotherapy in cancers with HLA class I defects

Abstract: DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB)1,2. Here, in contrast to other cancer types3-5, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8+ T cells in this context. We next identified a strong association between B2M inactivation and increased infiltration by γδ T cells in MMR-d cancers. These γδ T cells mainly comprised the Vδ1 and Vδ3 subsets, and expressed high levels of PD-1, other activation markers, including cytotoxic molecules, and a broad repertoire of killer-cell immunoglobulin-like receptors. In vitro, PD-1+ γδ T cells that were isolated from MMR-d colon cancers exhibited enhanced reactivity to human leukocyte antigen (HLA)-class-I-negative MMR-d colon cancer cell lines and B2M-knockout patient-derived tumour organoids compared with antigen-presentation-proficient cells. By comparing paired tumour samples from patients with MMR-d colon cancer that were obtained before and after dual PD-1 and CTLA-4 blockade, we found that immune checkpoint blockade substantially increased the frequency of γδ T cells in B2M-deficient cancers. Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy.

An emphasis on the interaction of signaling pathways highlights the role of miRNAs in the etiology and treatment resistance of gastric cancer.

Abstract: Gastric cancer (GC) is 4th in incidence and mortality rates globally. Several genetic and epigenetic factors, including microRNAs (miRNAs), affect its initiation and progression. miRNAs are short chains of nucleic acids that can regulate several cellular processes by controlling their gene expression. So, dysregulation of miRNAs expressions is associated with GC initiation, progression, invasion capacity, apoptosis evasions, angiogenesis, promotion and EMT enhancement. Of important pathways in GC and controlled by miRNAs are Wnt/β-catenin signaling, HMGA2/mTOR/P-gp, PI3K/AKT/c-Myc, VEGFR and TGFb signaling. Hence, this review was conducted to review an updated view of the role of miRNAs in GC pathogenesis and their modulatory effects on responses to different GC treatment modalities.

The interplay of signaling pathways with miRNAs in cholangiocarcinoma pathogenicity and targeted therapy.

Abstract: Cholangiocarcinoma (CCA), the second most frequent liver cancer after hepatocellular carcinoma, has been rising worldwide in recent epidemiological research. This neoplasia's pathogenesis is poorly understood. Yet, recent advances have illuminated the molecular processes of cholangiocyte malignancy and growth. Late diagnosis, ineffective therapy, and resistance to standard treatments contribute to this malignancy's poor prognosis. So, to develop efficient preventative and therapy methods, the molecular pathways that cause this cancer must be better understood. MicroRNAs (miRNAs) are non-coding ribonucleic acids (ncRNAs) that influence gene expression. Biliary carcinogenesis involves abnormally expressed miRNAs that act as oncogenes or tumor suppressors (TSs). The miRNAs regulate multiple gene networks and are involved in cancer hallmarks like reprogramming of cellular metabolism, sustained proliferative signaling, evasion of growth suppressors, replicative immortality, induction/access to the vasculature, activation of invasion and metastasis, and avoidance of immune destruction. In addition, numerous ongoing clinical trials are demonstrating the efficacy of therapeutic strategies based on miRNAs as powerful anticancer agents. Here, we will update the research on CCA-related miRNAs and explain their regulation involved in the molecular pathophysiology of this malignancy. Eventually, we will disclose their potential as clinical biomarkers and therapeutic tools in CCA.

A Chat(GPT) about the future of scientific publishing

Abstract: The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a “cold tumour,” a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and in vivo EOC models.Noradrenaline (NA), an adrenergic agonist, did not directly regulate PD-L1 expression but PD-L1 was significantly upregulated by IFN-γ in EOC cell lines. IFN-γ also increased PD-L1 on extracellular vesicles (EVs) released by ID8 cells. PRO significantly decreased IFN-γ levels in primary immune cells activated ex vivo and showed increased viability of the CD8+ cell population in an EV-immune cell co-incubation. In addition, PRO reverted PD-L1 upregulation and significantly decreased IL-10 levels in an immune-cancer cell co-culture. Chronic behavioural stress increased metastasis in mice while PRO monotherapy and the combo of PRO and PD-(L)1 inhibitor significantly decreased stress-induced metastasis. The combined therapy also reduced tumour weight compared to the cancer control group and induced anti-tumour T-cell responses with significant CD8 expression in tumour tissues. In conclusion, PRO showed a modulation of the cancer immune response by decreasing IFN-γ production and, in turn, IFN-γ-mediated PD-L1 overexpression. The combined therapy of PRO and PD-(L)1 inhibitor decreased metastasis and improved anti-tumour immunity offering a promising new therapy.

miRNAs as potential game-changers in head and neck cancer: Future clinical and medicinal uses.

Abstract: Head and neck cancers (HNCs) are a group of heterogeneous tumors formed most frequently from epithelial cells of the larynx, lips, oropharynx, nasopharynx, and mouth. Numerous epigenetic components, including miRNAs, have been demonstrated to have an impact on HNCs characteristics like progression, angiogenesis, initiation, and resistance to therapeutic interventions. The miRNAs may control the production of numerous genes linked to HNCs pathogenesis. The roles that miRNAs play in angiogenesis, invasion, metastasis, cell cycle, proliferation, and apoptosis are responsible for this impact. The miRNAs also have an impact on crucial HNCs-related mechanistic networks like the WNT/β-catenin signaling, PTEN/Akt/mTOR pathway, TGFβ, and KRAS mutations. miRNAs may affect how the HNCs respond to treatments like radiation and chemotherapy in addition to pathophysiology. This review aims to demonstrate the relationship between miRNAs and HNCs with a particular emphasis on how miRNAs impact HNCs signaling networks.

Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination

Abstract: PURPOSE Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136 ). METHODS Eligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte–associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg intravenously once every 3 weeks until PD or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST, version 1.1, by independent central review. RESULTS A total of 103 patients were enrolled and treated. The median study follow-up was 15.3 months. ORR in the total population was 21.4% (95% CI, 13.9 to 30.5), with three (2.9%) complete responses and 19 (18.4%) partial responses. The median duration of response was 8.3 months (range, 3.2-15.9+). ORR was 33.3% in the 30 patients with PD on prior anti–PD-1 plus anti–CTLA-4 therapy. The median progression-free survival and overall survival in the total population were 4.2 months (95% CI, 3.8 to 7.1) and 14.0 months (95% CI, 10.8 to not reached), respectively. Grade 3-5 treatment-related adverse events occurred in 47 (45.6%) patients, most commonly hypertension (21.4%); one patient died from a treatment-related event (decreased platelet count). CONCLUSION Lenvatinib plus pembrolizumab provides clinically meaningful, durable responses in patients with advanced melanoma with confirmed PD on prior PD-1/L1 inhibitor-based therapy, including those with PD on anti–PD-1 plus anti–CTLA-4 therapy. The safety profile was as expected. These data support lenvatinib plus pembrolizumab as a potential regimen for this population of high unmet need.

miRNAs as potential game-changers in renal cell carcinoma: Future clinical and medicinal uses.

Abstract: Renal cell carcinoma (RCC) has the highest mortality rate of all genitourinary cancers, and its prevalence has grown over time. While RCC can be surgically treated and recurrence is only probable in a tiny proportion of patients, early diagnosis is crucial. Mutations in a large number of oncogenes and tumor suppressor genes contribute to pathway dysregulation in RCC. MicroRNAs (miRNAs) have considerable promise as biomarkers for detecting cancer due to their special combination of properties. Several miRNAs have been proposed as a diagnostic or monitoring tool for RCC based on their presence in the blood or urine. Moreover, the expression profile of particular miRNAs has been associated with the response to chemotherapy, immunotherapy, or targeted therapeutic options like sunitinib. The goal of this review is to go over the development, spread, and evolution of RCC. Also, we emphasize the outcomes of studies that examined the use of miRNAs in RCC patients as biomarkers, therapeutic targets, or modulators of responsiveness to treatment modalities.

Role of long non-coding RNAs in pancreatic cancer pathogenesis and treatment resistance- A review.

Abstract: Pancreatic cancer (PC) is one of the deadliest cancers associated with poor prognosis. The lack of reliable means of early cancer detection contributes to this disease's dismal prognosis. Long non-coding RNAs (LncRNAs) are protein-free RNAs produced by genome transcription; they play critical roles in gene expression regulation, epigenetic modification, cell proliferation, differentiation, and reproduction. Recent research has shown that lncRNAs play important regulatory roles in PC behaviors, in addition to their recently found functions. Several in-depth investigations have shown that lncRNAs are strongly linked to PC development and progression. Here, we discuss how lncRNAs, which are often overlooked, play many roles as regulators in the molecular mechanism underlying PC. This review also discusses the involved LncRNAs in PC pathogenesis and treatment resistance.

A spotlight on the interplay of signaling pathways and the role of miRNAs in osteosarcoma pathogenesis and therapeutic resistance.

Abstract: Osteosarcoma (OS) is one of the most common bone cancers that constantly affects children, teenagers, and young adults. Numerous epigenetic elements, such as miRNAs, have been shown to influence OS features like progression, initiation, angiogenesis, and treatment resistance. The expression of numerous genes implicated in OS pathogenesis might be regulated by miRNAs. This effect is ascribed to miRNAs' roles in the invasion, angiogenesis, metastasis, proliferation, cell cycle, and apoptosis. Important OS-related mechanistic networks like the WNT/b-catenin signaling, PTEN/AKT/mTOR axis, and KRAS mutations are also affected by miRNAs. In addition to pathophysiology, miRNAs may influence how the OS reacts to therapies like radiotherapy and chemotherapy. With a focus on how miRNAs affect OS signaling pathways, this review seeks to show how miRNAs and OS are related.

Understanding the role of the gut microbiome in gastrointestinal cancer: A review

Abstract: Gastrointestinal cancer represents one of the most diagnosed types of cancer. Cancer is a genetic and multifactorial disease, influenced by the host and environmental factors. It has been stated that 20% of cancer is caused by microorganisms such as Helicobacter pylori, hepatitis B and C virus, and human papillomavirus. In addition to these well-known microorganisms associated with cancer, it has been shown differences in the composition of the microbiota between healthy individuals and cancer patients. Some studies have suggested the existence of the selected microorganisms and their metabolites that can promote or inhibit tumorigenesis via some mechanisms. Recent findings have shown that gut microbiome and their metabolites can act as cancer promotors or inhibitors. It has been shown that gastrointestinal cancer can be caused by a dysregulation of the expression of non-coding RNA (ncRNA) through the gut microbiome. This review will summarize the latest reports regarding the relationship among gut microbiome, ncRNAs, and gastrointestinal cancer. The potential applications of diagnosing and cancer treatments will be discussed.

The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis

Abstract: Abstract Pancreatic cancer is characterized by abundant desmoplasia, a dense stroma composed of extra-cellular and cellular components, with cancer associated fibroblasts (CAFs) being the major cellular component. However, the tissue(s) of origin for CAFs remains controversial. Here we determine the tissue origin of pancreatic CAFs through comprehensive lineage tracing studies in mice. We find that the splanchnic mesenchyme, the fetal cell layer surrounding the endoderm from which the pancreatic epithelium originates, gives rise to the majority of resident fibroblasts in the normal pancreas. In a genetic mouse model of pancreatic cancer, resident fibroblasts expand and constitute the bulk of CAFs. Single cell RNA profiling identifies gene expression signatures that are shared among the fetal splanchnic mesenchyme, adult fibroblasts and CAFs, suggesting a persistent transcriptional program underlies splanchnic lineage differentiation. Together, this study defines the phylogeny of the mesenchymal component of the pancreas and provides insights into pancreatic morphogenesis and tumorigenesis.