Current Cancer Treatment Research Articles

Experimental Animal Models for Preclinical Investigation of the Bladder Cancer

Abstract: The current treatments for bladder cancer are unable to substantially avoid the disease's growth and recurrence, which is a serious public health problem. Researchers have explored a variety of approaches in an effort to effectively replicate the pathophysiology of human tumors using experimental tumor models. The investigation of the available models is a necessary tool in order to choose the most appropriate scheme which serves the translation of potential treatments from a primary experimental bench to the clinical settings. The most suitable murine models of bladder cancer should have excellent reproductivity, intravesical predictability, and accessibility in order to facilitate the mechanistic, chemopreventive, and therapeutic research that can be expanded into clinical trials. This article provides a complete evaluation of both in vitro and in vivo bladder cancer models, comparing their advantages and limitations in urological research.

Construction of Lung Adenocarcinoma Prognosis Model and Drug Sensitivity Analysis Based on Cuproptosis Related Genes

Lung cancer is one of the most common malignant tumors in the world, and the current lung cancer screening and treatment strategies are constantly improving, but its 5-year survival rate is still very low, which seriously endangers human health. Therefore, it is critical to explore new biomarkers to provide personalized treatment and improve the prognosis. Cuproptosis is a newly discovered type of cell death, which is due to the accumulation of excess copper ions in the cell, eventually leading to cell death, which has been suggested by studies to be closely related to the occurrence and development of lung adenocarcinoma (LUAD). Based on The Cancer Genome Atlas (TCGA) database, this study explored the association between cuproptosis-related genes (CRGs) and LUAD prognosis, established a prognostic risk model, and analyzed the interaction between CRGs and LUAD immune cell infiltration. The RNA-seq data of LUAD tissue and paracancerous or normal lung tissue were downloaded from the TCGA database; the RNA-seq data of normal lung tissue was downloaded from the Genotype-tissue Expression (GTEx) database, and the data of 462 lung adenocarcinoma cases were downloaded from the Gene Expression Omnibus repository (GEO) as verification. T the risk score model to assess prognosis was constructed by univariate Cox and Lasso-Cox regression analysis, and the predictive ability of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Immune-related and drug susceptibility analysis was further performed on high- and low-risk groups. A total of 1656 CRGs and 1356 differentially expressed CRGs were obtained, and 13 CRGs were screened out based on univariate Cox and Lasso-Cox regression analysis to construct a prognostic risk model, and the area under the curves (AUCs) of ROC curves 1-, 3- and 5- year were 0.749, 0.740 and 0.689, respectively. Further study of immune-related functions and immune checkpoint differential analysis between high- and low-risk groups was done. High-risk groups were more sensitive to drugs such as Savolitinib, Palbociclib, and Cytarabine and were more likely to benefit from immunotherapy. The risk model constructed based on 13 CRGs has good prognostic value, which can assist LUAD patients in individualized treatment, and provides an important theoretical basis for the treatment and prognosis of LUAD.

Carcinoma buccal mucosa treated with definitive hypofractionated accelerated radiotherapy: a retrospective analysis of treatment outcomes.

Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS (P = 0.026) and OS (P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.

Robotic Rectal Resection for Rectal Cancer in Elderly Patients: A Systematic Review and Meta-Analysis.

Rectal cancer is estimated to increase due to an expanding aging population, thus affecting elderly patients more frequently. The optimal surgical treatment for this type of patient remains controversial because they are often excluded from or underrepresented in trials. This meta-analysis aimed to evaluate the feasibility and the safety of robotic surgery in elderly patients (>70 years old) undergoing curative treatment for rectal cancer. Studies comparing elderly (E) and young (Y) patients submitted to robotic rectal resection were searched on PubMed, Embase, and the Cochrane Library. Data regarding surgical oncologic quality, post-operative, and survival outcomes were extracted. Overall, 322 patients underwent robotic resection (81 in the E group and 241 in the Y group) for rectal cancer. No differences between the two groups were found regarding distal margins and the number of nodes yielded (12.70 in the E group vs. 14.02 in the Y group, p = 0.16). No differences were found in conversion rate, postoperative morbidity, mortality, and length of stay. Survival outcomes were only reported in one study. The results of this study suggest that elderly patients can be submitted to robotic resection for rectal cancer with the same oncologic surgical quality offered to young patients, without increasing postoperative mortality and morbidity.

Impact of the time interval between primary or interval surgery and adjuvant chemotherapy in ovarian cancer patients.

Primary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes. We conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation. Among the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04-3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75-3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50-4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients. In conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease.

Radiotherapy-induced Immune Response Enhanced by Selective HDAC6 Inhibition.

Radiotherapy is a curative cancer treatment modality that imparts damage to cellular DNA, induces immunogenic cell death, and activates antitumor immunity. Despite the radiotherapy-induced direct antitumor effect seen within the treated volume, accumulating evidence indicates activation of innate antitumor immunity. Acute proinflammatory responses mediated by anticancer M1 macrophages are observed in the immediate aftermath following radiotherapy. However, after a few days, these M1 macrophages are converted to anti-inflammatory and pro-cancer M2 phenotype, leading to cancer resistance and underlying potential tumor relapse. Histone deacetylase 6 (HDAC6) plays a crucial role in regulating macrophage polarization and innate immune responses. Here, we report targeting HDAC6 function with a novel selective inhibitor (SP-2-225) as a potential therapeutic candidate for combination therapy with radiotherapy. This resulted in decreased tumor growth and enhanced M1/M2 ratio of infiltrating macrophages within tumors. These observations support the use of selective HDAC6 inhibitors to improve antitumor immune responses and prevent tumor relapse after radiotherapy.

The association between hospital variation in curative treatment for esophagogastric cancer and health-related quality of life and survival

BackgroundAs previous studies showed significant hospital variation in curative treatment of esophagogastric cancer, this study assesses the association between this variation and overall, cancer-specific and recurrence-free survival, and Health-Related Quality of Life (HRQoL). MethodsPatients diagnosed with potentially curable esophageal or gastric cancer between 2015 and 2018 as registered in the Netherlands Cancer Registry were included. Data on overall survival was available for all patients, data on cancer-specific and recurrence-free survival and HRQoL was available for subgroups. Patients were classified according to diagnosis in hospitals with low, medium or high probability of treatment with curative intent (LP, MP or HP). Multivariable models were used to assess the association between LP, MP and HP hospitals and HRQoL and survival. ResultsThis study includes 7,199 patients with esophageal, and 2,407 with gastric cancer. Overall and cancer-specific survival was better for patients diagnosed in HP versus LP hospitals for both esophageal (HR = 0.82, 95%CI:0.77–0.88 and HR = 0.82, 95%CI:0.75–0.91, respectively), and gastric cancer (HR = 0.82, 95%CI:0.73–0.92 and HR = 0.74, 95%CI:0.64–0.87, respectively). These differences disappeared after adjustments for treatment. Recurrence-free survival was worse for gastric cancer patients diagnosed in HP hospitals (HR = 1.50, 95%CI:1.14–1.96), which disappeared after adjustment for radicality of surgery. Minor, but no clinically relevant, differences in HRQoL were observed. ConclusionsPatients diagnosed in hospitals with a high probability of treatment with curative intent have a better overall and cancer-specific but not recurrence-free survival, while minor differences in HRQoL were observed.

Wanita 74 Tahun Dengan Metastasis Pada Lobus Parieto-Oksipital Pada Melanoma Maligna

Melanoma is a tumor that is produced by the malignant transformation of melanocyte cells. Melanoma is the leading cause of premature death from cancer. Known risk factors include personal or family history of melanoma, large numbers of naevi and/or dysplastic naevi, congenital melanocytic naevi, sun-damaged skin, history of non-melanoma skin cancer, and immunodeficiency. Based on the Basic Health Research Results (Riskesdas) report, skin cancer as a whole ranks 3rd in Indonesia. Epidemiological studies of skin cancer have reported in Jakarta in 2014–2017, where out of 263 cases of skin cancer, malignant melanoma ranks third with the highest incidence of skin cancer (5.7%). Diagnosis of melanoma can be made by assessing the skin lesions with the naked eye and also by the patient's clinical symptoms. A person's risk of metastases is directly related to the depth of invasion and ulceration of their primary lesion. Among solid tumors, melanoma has one of the highest propensities to cause brain metastases with a proportion of more than 25% of patients. Although the current cancer treatment paradigm may reflect a combination of surgery, chemotherapy, radiotherapy, and immunotherapy with medical management, options for the treatment of metastatic brain cancer remain limited.

The Relationship Between Gene Mutations and the Clinicopathological Features and Prognosis of Gastric Cancer.

Current treatments for gastric cancer (GC) are suboptimal. Potential therapeutic targets for GC were screened using next-generation sequencing. We examined many mutation genes linked to GC, including TP53 (60%), PIK3CA (19%), LRP1B (13%), and ERBB2 (12%), ARID1A (9%), KMT2C (9%), and KRAS (7%). The KMT2C, KRAS, CDK6, and ARID1A wild-type genes were dominant in diffuse-type GC (P < .05), but mutations did not influence prognosis. Patients with APC (6%) and CDH1 (8%) wild-type GC presented with vascular invasion (P < .05). Patients with ATR (2%) wild-type GC were prone to lymph node metastasis (P < .05). Patients with ARID1A (9%) wild-type GC had reduced programmed death ligand 1 expression (<1, P < .05). We found that patients who received chemotherapy had a better prognosis than those who did not (although there was no statistical difference), with platinum-based group having better prognosis and uracil combined with paclitaxel group having worse prognosis.

Can We Predict Prostate Cancer Metastasis Based on Biomarkers? Where Are We Now?

The incidence of prostate cancer (PC) has risen annually. PC mortality is explained by the metastatic disease (mPC). There is an intermediate scenario in which patients have non-mPC but have initiated a metastatic cascade through epithelial-mesenchymal transition. There is indeed a need for more and better tools to predict which patients will progress in the future to non-localized clinical disease or already have micrometastatic disease and, therefore, will clinically progress after primary treatment. Biomarkers for the prediction of mPC are still under development; there are few studies and not much evidence of their usefulness. This review is focused on tissue-based genomic biomarkers (TBGB) for the prediction of metastatic disease. We develop four main research questions that we attempt to answer according to the current evidence. Why is it important to predict metastatic disease? Which tests are available to predict metastatic disease? What impact should there be on clinical guidelines and clinical practice in predicting metastatic disease? What are the current prostate cancer treatments? The importance of predicting metastasis is fundamental given that, once metastasis is diagnosed, quality of life (QoL) and survival drop dramatically. There is still a need and space for more cost-effective TBGB tests that predict mPC disease.

Evaluation of Nationwide Trends in Nodal Sampling Guideline Adherence for Gastric Cancer: 2005-2017

IntroductionSurgical resection is the primary curative treatment for localized gastric cancer. A multitude of research supports surgical nodal sampling guidelines. Though there are known disparities in adherence to nodal sampling, it is unclear how hospital program-level disparities have changed over time. The purpose of this study is to evaluate trends in program-level disparities in adherence to gastric cancer nodal sampling guidelines. MethodsPatients who underwent resection of gastric cancer from 2005 to 2017 were identified in the National Cancer Database. Patients treated at academic programs were compared to those treated at nonacademic programs, and rates and trends of adherence to nodal sampling guidelines (defined as ≥15 lymph nodes) were determined. Adjusted multivariable analysis was used to determine likelihood of nodal sampling adherence while controlling for sociodemographic, clinical, hospital, and travel distance characteristics. ResultsA total of 55,421 patients were included with 27,201 (49.1%) of patients meeting adherence criteria for lymph node sampling. Academic programs treated 44.4% of the total cohort. Overall, lymph node sampling criteria were met in 59.2% of patients treated at high-volume academic programs and 37.0% of patients treated at low-volume nonacademic programs (incidence rate ratios 0.67, 95% confidence interval 0.63-0.72 versus high-volume academic programs). Adherence rates improved from 2005 to 2017 for both low-volume nonacademic programs (27.8% in 2005 to 50.1% in 2017) and high-volume academic programs (46.0% in 2005 to 69.8% in 2017, P < 0.001). ConclusionsThough adherence rates have improved from 2005 to 2017, high-volume academic programs were more likely to adhere to lymph node sampling guidelines for gastric cancer.

Cabazitaxel-loaded human serum albumin nanoparticles combined with TGFβ-1 siRNA lipid nanoparticles for the treatment of paclitaxel-resistant non-small cell lung cancer

BackgroundIn the current treatment of non-small cell lung cancer (NSCLC), traditional chemotherapy causes high toxicity, so it is necessary to develop safe chemical drug delivery vehicles clinically. Chemotherapy monotherapy is prone to drug resistance. Chemotherapy combined with other therapies such as nucleic acid drugs is an effective way to avoid drug resistance and the toxicity of continuous chemotherapy. In this study, chemotherapy and siRNA therapy were combined to treat paclitaxel-resistant NSCLC in order to increase efficacy and reduce toxicity. This study aims to develop a cabazitaxel-loaded human serum albumin nanoparticles (CTX-HSA-NPs) to improve the toxicity of traditional CTX-Tween 80 and increase targeting, and to develop a TGFβ-1 siRNA lipid Nanoparticles (TGFβ-1 siRNA LNP) combined with chemotherapy in the treatment of paclitaxel-resistant NSCLC.ResultsThis study prepared CTX-HSA-NPs and TGFβ-1 siRNA LNP had small particle size, high encapsulation efficiency (EE). CTX-HSA-NPs lyophilized powder has high stability after dissolved. The antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was 1.8 times lower than that of CTX-Tween. More importantly, the combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC in vivo and in vitro. The results of tumor immunohistochemistry showed that TGFβ-1 siRNA LNP significantly inhibited the expression of TGFβ-1, and compared with other groups, the expression of P-gp after low-dose CTX-HSA-NPs treatment was lower, which did not cause obvious drug resistance.ConclusionsThe antitumor effect of CTX-HSA-NPs on paclitaxel-resistant NSCLC was higher than that of CTX-Tween, and the toxicity was lower than that of CTX-Tween. TGFβ-1 siRNA LNP can treat paclitaxel-resistant NSCLC by inhibiting the express of TGFβ-1 mRNA. The combined treatment of TGFβ-1 siRNA LNP and CTX-HSA-NPs could effectively improve the antitumor efficacy of paclitaxel-resistant NSCLC. A combination therapy of chemotherapy and nucleic acid drugs could be an effective approach for treating paclitaxel-resistant NSCLC.

Updates and advances in the concept of gallbladder cancer treatment

The gallbladder is the most common site of tumor occurrence among biliary tract cancer. Gallbladder cancer accounts for approximately 0.6% of new cancers and 0.9% of cancer-related deaths. The risk factors identified for the development of gallbladder cancer include being female,>65 years of age, asymptomatic gallstone disease,and obesity. Surgical resection is the only curative treatment for early-stage gallbladder cancer, and some intermediate or advanced gallbladder cancers can be radically cured by extended resection. However, the extent of liver resection or lymph node dissection and whether to combine it with bile duct removal, revascularisation,and multiple organ resection remain somewhat controversial. After neoadjuvant treatment, up to a third of patients with locally advanced gallbladder cancer benefit from secondary surgical treatment. Only a small proportion of patients with gallbladder cancer at high risk for recurrence will benefit from postoperative adjuvant therapy. With the advent of different target-targeted drugs and the use of genetic tests in biliary tract cancer, targeted therapy and PD-1/PD-L1 inhibitors may become the new standard of care for gallbladder cancer and need to be further explored.

Current systemic treatment for pancreatic cancer

Current systemic treatment for pancreatic cancer

Curative treatment for stage IIIC2 cervical cancer: what to expect?

Since the GOG125 study, treating radically patients with positive para-aortic lymph nodes has been a valid approach. Nevertheless, literature lacks data on how to better treat these patients since they are usually excluded from trials. In this study, we aimed to report the outcomes of patients with advanced cervical cancer and positive para-aortic lymph nodes (PAN) treated in a single tertiary/academic institution and try to identify variables that may impact survival. We retrospectively reviewed patients with positive para-aortic lymph nodes treated in our institution. Demographic variables and treatment options were assessed and their impact on overall survival (OS), locorregional control, distant metastasis free survival, and para-aortic lymph node progression was analyzed. We assessed 65 patients treated from April 2010 to May 2017. Median OS was 38.7 months. Median locorregional and para-aortic progression free survivals were not reached. Median distant metastasis progression-free survival was 64.3 months. Better ECOG performance status (p > 0.001), concurrent chemotherapy (p = 0.031), and brachytherapy (p = 0.02) were independently related to better overall survival. Patients with current stage IIIC2 cervix cancer may present long term survival. Treating positive PAN cervical cancer patients with concurrent chemoradiation including brachytherapy with curative intent should be standard. Poor PS and more advanced pelvic disease may represent a higher risk for worse outcomes. Distant metastases are still a challenge for disease control.

Advances in Management of Ovarian Cancer through Natural Resources: An Update

Since times immemorial, mankind has been dependent on Mother Nature in terms of natural resources for alleviating its sufferings. As per W.H.O., developing countries should fully explore their flora and fauna to become economically self-reliant. Country India enjoys having diverse climatic conditions of heavy rainfall, sandy deserts &amp; snow-clad mountains, which play a perfect condition and host for the growth of plenty of medicinal plants with desirable phytoconstituents. Presently mankind is suffering from many diseases that were not so common in the olden days. Does it is a signal from our mother Nature to once again rediscover its treasure of natural resources for exploring answers for various prophylaxis and therapeutic needs of modern-day disorders and diseases? Cancer is the most fatal disease worldwide caused due to the uncontrolled growth of abnormal cells in the body. Ovarian Cancer is the fifth leading cause of death in females. The incidence and mortality rate of Ovarian Cancer is increasing day by day across the world. Biomarkers such as CA125, HE4, OVA1, and Cancer stem cells have been used for the detection of Ovarian Cancer. The current treatment of Ovarian Cancer is surgery and some common treatments include chemotherapy, radiation therapy, adoptive cell therapy, use of medicinal plants and their derivatives. Some prominent medicinal plants like Quercus tinctoria, Curcuma longa, Taxus brevifolia, Allium sativum, Asparagus racemosa, Camptotheca acuminate, Symplocus racemosa, Ginkgo biloba, Genistein, Zingiber officinale, Azadirachta indica, Embilica officinalis, Podophyllum peltatum, Camellia sinensis, Saraca indica. A large number of phytochemicals which has anticancer compounds are flavonoids, alkaloids, terpenoids, carotenoids, phenolics, and organosulfur compounds. Ayurvedic drugs highly effective on Ovarian Cancer are Arka, Bhallataka, Ahipena, Bhanga, Vishamushti, and Jayapala. The diagnosis of Ovarian Cancer in the initial stage is not possible mainly due to a lack of awareness on patients’ behalf. The main effective parameter is imaging for checking the extent and location of the disease. Some other parameters also included physical examination and transvaginal ultrasonography. Thus, the present review is an attempt to compile published reports through authentic sources regarding the current management scenario of Ovarian Cancer with the help of natural drugs or medicinal plants that inhibits or hinders the growth of cancer cell, which may serve as a ready reference for future researchers.

Patient Experiences of a Telehealth Multidisciplinary Cancer Rehabilitation Programme: Qualitative Findings from the ReStOre@Home Feasibility Study

Purpose. Multidisciplinary rehabilitation programmes providing exercise, nutrition support, education, and peer support can effectively meet the rehabilitation needs of upper gastrointestinal (UGI) cancer survivors. This study aimed to explore the experiences of participants who engaged in a telehealth, multidisciplinary rehabilitation programme for UGI cancer survivors. Methods. This single-arm feasibility study recruited participants who completed curative treatment for UGI cancer. Participants (n = 10, male = 9) aged 58–76 years were 5–17 months postsurgery. A 12-week telehealth rehabilitation programme was delivered via video call, consisting of group resistance training, remotely monitored aerobic training, 1 : 1 dietary counselling, 1 : 1 physiotherapy support, and group education sessions. Independent researchers conducted semistructured interviews at postintervention assessments. Transcripts were analysed using reflexive thematic analysis (RTA). Results. RTA of participant transcripts generated three overarching themes: (1) ReStOre@Home impacted psychosocial and physical needs by addressing a broad and meaningful gap in services, (2) paving a pathway towards prosperity, and (3) contrasting experiences with using technology. Participants’ preferences and recommendations for future telehealth programmes were discussed. Conclusions. A telehealth multidisciplinary rehabilitation programme supported participants in physical and psychosocial recovery. Qualitative analysis identified an important ongoing need for some in-person care and provided detailed insights into participant experiences during telehealth-delivered rehabilitation.

The Contribution of Cancer-Specific Psychosocial Factors to the Pain Experience in Cancer Survivors.

Palliative care teams are increasingly called up to manage chronic pain in cancer survivors. Chronic pain is common in cancer survivors and is heavily influenced by biopsychosocial factors. This study aimed to determine the relative contribution of unique cancer-specific psychosocial factors, pain catastrophizing, and multisite pain to the pain experience in 41 cancer survivors who completed curative cancer treatment. To test the research hypotheses, a series of nested linear regression models were used with likelihood ratio testing to test the individual and collective contribution of cancer-specific psychosocial factors (fear of cancer recurrence, cancer distress, cancer-related trauma), pain catastrophizing, and the number of pain sites on the pain experience. The results indicate pain catastrophizing and multisite pain explained a significant degree of variance in pain interference scores ( P < .001) and pain severity ( P = .005). Cancer-specific psychosocial factors did not significantly predict variability in pain interference ( P = .313) or pain severity ( P = .668) over and above pain catastrophizing and the number of sites of pain. In summary, pain catastrophizing and multisite pain contribute to the chronic cancer-related pain experienced by cancer survivors. Palliative care nurses are well positioned to improve chronic pain among cancer survivors by assessing and treating pain catastrophizing and multisite pain.

State-of-the-Art and Upcoming Innovations in Pancreatic Cancer Care: A Step Forward to Precision Medicine

Pancreatic cancer remains a social and medical burden despite the tremendous advances that medicine has made in the last two decades. The incidence of pancreatic cancer is increasing, and it continues to be associated with high mortality and morbidity rates. The difficulty of early diagnosis (the lack of specific symptoms and biomarkers at early stages), the aggressiveness of the disease, and its resistance to systemic therapies are the main factors for the poor prognosis of pancreatic cancer. The only curative treatment for pancreatic cancer is surgery, but the vast majority of patients with pancreatic cancer have advanced disease at the time of diagnosis. Pancreatic surgery is among the most challenging surgical procedures, but recent improvements in surgical techniques, careful patient selection, and the availability of minimally invasive techniques (e.g., robotic surgery) have dramatically reduced the morbidity and mortality associated with pancreatic surgery. Patients who are not candidates for surgery may benefit from locoregional and systemic therapy. In some cases (e.g., patients for whom marginal resection is feasible), systemic therapy may be considered a bridge to surgery to allow downstaging of the cancer; in other cases (e.g., metastatic disease), systemic therapy is considered the standard approach with the goal of prolonging patient survival. The complexity of patients with pancreatic cancer requires a personalized and multidisciplinary approach to choose the best treatment for each clinical situation. The aim of this article is to provide a literature review of the available treatments for the different stages of pancreatic cancer.

Stromal cell-derived small extracellular vesicles enhance radioresistance of prostate cancer cells via interleukin-8-induced autophagy.

Radiation is a curative treatment for localized prostate cancer (PCa). Unfortunately, radiotherapeutic efficacy is often diminished when patients develop more aggressive or metastatic phenotypes. Recent studies have demonstrated that extracellular vesicles participate in cancer therapeutic resistance by delivering small bioactive molecules, such as small non-coding RNAs. Here, we show that stromal cell-derived small extracellular vesicles (sEVs) facilitate the radioresistance of PCa cells by transporting interleukin-8 (IL-8). Indeed, prostatic stromal cells secrete more IL-8 than AR-positive PCa cells, which can be accumulated in sEVs. Intriguingly, the uptake of stromal cells-derived sEVs by radiosensitive PCa cells enhanced their radioresistance, which could be attenuated by silencing CXCL8 in stromal cells or inhibiting its receptor CXCR2 in PCa cells. sEV-mediated radioresistance has been validated in zebrafish and mouse xenograft tumours. Mechanistically, the uptake of stromal sEVs triggers the AMPK-activated autophagy pathway in PCa cells under the irradiation condition. Consequently, inactivating AMPK efficiently resensitized radiotherapy either by utilizing an AMPK inhibitor or silencing AMPKα in PCa cells. Furthermore, chloroquine (CQ), a lysosomal inhibitor, sufficiently resensitized radiotherapy via blockade of autophagolysosome fusion, leading to autophagosome accumulation in PC cells. Collectively, these results suggest that stromal cells enhance the radioresistance of PCa cells mainly through sEVs that deliver IL-8.