Implications For Chemotherapy Research Articles

Histone acetylation risk model predicts prognosis and guides therapy selection in glioblastoma: implications for chemotherapy and anti-CTLA-4 immunotherapy

BackgroundGlioblastoma is characterized by high aggressiveness, frequent recurrence, and poor prognosis. Histone acetylation-associated genes have been implicated in its occurrence and development, yet their predictive ability in glioblastoma prognosis remains unclear.ResultsThis study constructs a histone acetylation risk model using Cox and LASSO regression analyses to evaluate glioblastoma prognosis. We assessed the model’s prognostic ability with univariate and multivariate Cox regression analyses. Additionally, immune infiltration was evaluated using ESTIMATE and TIMER algorithms, and the SubMAP algorithm was utilized to predict responses to CTLA4 inhibitor. Multiple drug databases were applied to assess drug sensitivity in high- and low-risk groups. Our results indicate that the histone acetylation risk model is independent and reliable in predicting prognosis.ConclusionsLow-risk patients showed higher immune activity and longer overall survival, suggesting anti-CTLA4 immunotherapy suitability, while high-risk patients might benefit more from chemotherapy. This model could guide personalized therapy selection for glioblastoma patients.

Implications of Chemotherapy, Radiation therapy, and Surgical treatment in Oral Cancer

Oral cancer includes both the cancers of the mouth and back of the throat. This literature review investigates viable treatment modalities for adult patients diagnosed with oral cancer including the comparison of chemo/radiation therapy, surgery, and new treatment modalities. Surgical interventions are often the initial treatment, depending on tumor characteristics, and may require reconstructive procedures. Chemotherapy and radiation therapy, while effective, present challenges such as side effects such as nausea, vomiting, hair loss, and fatigue. With surgery, there is the consideration of different types of therapies. Post-operative care, lifestyle implications, and treatment success vary among these modalities. New treatments such as gene therapy and immunotherapy are also starting to appear. Findings suggest the drawbacks and the advantages of different treatments and possible preventive measures.

Abstract B043: Challenges in managing cancer patients with congenital coronary artery anomalies: A case report

Abstract Introduction: Congenital coronary artery anomalies are rare cardiac abnormalities that can increase the risk of sudden cardiac death, particularly during exercise. Patients with cancer and concurrent coronary artery disease face higher mortality risks, as they often receive delayed percutaneous coronary intervention. Additionally, anthracycline chemotherapy, commonly used in cancer treatment, can cause cardiotoxicity and worsen pre-existing cardiac abnormalities. Despite the complexity of managing cancer patients with coronary artery anomalies, there is a lack of clear guidelines and consensus on optimal approaches. This report presents a unique case of a patient with a malignant inter-arterial course of the right coronary artery and newly diagnosed Human T-lymphotropic virus type I-associated adult T-cell leukemia/lymphoma, discussing the challenges and implications of chemotherapy in such cases. Case Presentation: A 38-year-old male presented with weakness and palpitations, exhibiting abnormal laboratory findings. CT angiography revealed a malignant inter-arterial course of the right coronary artery with severe narrowing. Electrocardiograms showed ST elevations and subsequent T-wave inversions. Despite the increased risk of cardiomyopathy due to the coronary anomaly, the patient required chemotherapy for life-threatening tumor lysis syndrome and refractory lactic acidosis. Anthracycline-based chemotherapy was initiated, and a follow-up echocardiogram after six months showed no acute changes. Conclusion: Managing cancer patients receiving anthracycline chemotherapy remains challenging due to limited guidelines. Anthracycline-induced cardiotoxicity is a concern, especially in patients with pre-existing cardiac anomalies like the malignant inter-arterial course of the right coronary artery. This case emphasizes the importance of recognizing and managing such anomalies in cancer patients to reduce the risk of sudden cardiac death. The higher mortality risk in cancer patients with coronary artery disease highlights the need for guidelines in managing anomalous coronary vessels in cancer patients. Further research is necessary to develop evidence-based strategies for managing cardiac complications in cancer patients, particularly those with pre-existing cardiac anomalies. Citation Format: Aliya M. Khan, Sophia Navajas Urisote, Danish A. Sheikh. Challenges in managing cancer patients with congenital coronary artery anomalies: A case report [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B043.

Stem Cells: Therapeutic Implications in Chemotherapy and Radiotherapy Resistance in Cancer Therapy.

Cancer stem cells (CSCs) are transformed forms of normal stem cells within heterogeneous mixture of cancer cells. These are mainly responsible for the recurrence of cancer after treatment because of their ability to develop resistance against chemo and radiotherapy due to various factors such as activation of signalling pathways important for self-renewal, DNA repair capacity, microenvironment and expression of ABC transporters. Targeting these mechanisms as potential factors can eliminate CSCs, which eventually decreases cancer recurrence. This review focuses on the characteristics of CSCs, their role in the development of resistance to chemotherapy and radiotherapy along with the therapeutic potential targets for successful elimination of CSC population.

Sensitivity analysis unveils the interplay of drug-sensitive and drug-resistant Glioma cells: Implications of chemotherapy and anti-angiogenic therapy

<abstract><p>This study presented a glioma growth model that accounts for drug-sensitive and drug-resistant cells in response to chemotherapy and anti-angiogenic therapy. Chemotherapy induces mutations in drug-sensitive cells, leading to the emergence of drug-resistant cells and highlighting the benefits of combined therapy. Anti-angiogenic therapy can mitigate mutations by inducing angiogenic dormancy. We have identified two reproduction numbers associated with the non-cell and disease-free states. Numerical sensitivity analysis has highlighted influential parameters that control glioma growth dynamics, emphasizing the interactions between drug-sensitive and drug-resistant cells. To reduce glioma endemicity among sensitive cases, it was recommended to decrease chemotherapy expenditure, increase angiogenic dormancy, and adjust chemotherapy infusion rates. In addition, to combat resistance to glioma endemicity, enhancing angiogenic dormancy is crucial.</p></abstract>

Drug resistance dependent on allostery: A P-loop rigor Eg5 mutant exhibits resistance to allosteric inhibition by STLC.

The mitotic kinesin Eg5 has emerged as a potential anti-mitotic target for the purposes of cancer chemotherapy. Whether clinical resistance to these inhibitors can arise is unclear. We exploited HCT116 cancer cell line to select resistant clones to S-trityl-L-cysteine (STLC), an extensively studied Eg5 loop-L5 binding inhibitor. The STLC resistant clones differed in their resistance to other loop-L5 binding inhibitors but remained sensitive to the ATP class of competitive Eg5 specific inhibitors. Eg5 is still necessary for bipolar spindle formation in the resistant clones since the cells were sensitive to RNAi mediated depletion of Eg5. One clone expressing Eg5(T107N), a dominant point mutation in the P-loop of the ATP binding domain of the motor, appeared to be not only resistant but also dependent on the presence of STLC. Eg5(T107N) expression was associated also with resistance to the clinical relevant loop-L5 Eg5 inhibitors, Arry-520 and ispinesib. Ectopic expression of the Eg5(T107N) mutant in the absence of STLC was associated with strong non-exchangeable binding to microtubules causing them to bundle. Biochemical assays showed that in contrast to the wild type Eg5-STLC complex, the ATP binding site of the Eg5(T107N) is accessible for nucleotide exchange only when the inhibitor is present. We predict that resistance can be overcome by inhibitors that bind to other than the Eg5 loop-L5 binding site having different chemical scaffolds, and that allostery-dependent resistance to Eg5 inhibitors may also occur in cells and may have positive implications in chemotherapy since once diagnosed may be beneficial following cessation of the chemotherapeutic regimen.

The viral capsid as novel nanomaterials for drug delivery.

The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging.

The Role of Chemotherapy in Patients With HER2-Negative Isolated Locoregional Recurrence of Breast Cancer: A Multicenter Retrospective Cohort Study.

Background: The role of chemotherapy for isolated locoregional recurrence (iLRR) of breast cancer has not been firmly established after local therapies.Methods: We performed a multicenter, retrospective analysis to evaluate the clinical implications of chemotherapy in breast cancer patients with HER2-negative iLRR.Results: Of a total of 277 patients, 146 (52.7%) received chemotherapy for iLRR. Median follow-up duration was 56.1 months. Eighty-six (31.0%) patients had luminal B-like and 100 (36.1%) had TNBC iLRR. There was a trend of longer disease free survival (DFS) in the chemotherapy group (4-year DFS: 70.4 vs. 59.5%, HR = 0.68, 95% CI 0.45–1.02, log-rank p = 0.059). When adjusted with clinically relevant factors, DFS was significantly prolonged with chemotherapy (adjusted HR = 0.61, 95% CI 0.40–0.94, p = 0.023). Subgroup analyses for DFS showed patients with disease free interval (DFI) <5 years or prior chemotherapy had a benefit from chemotherapy (adjusted HR = 0.57, p = 0.018; adjusted HR = 0.51, p = 0.005, respectively). Regarding the molecular subtypes, a longer DFS with chemotherapy was observed both in luminal B-like (4-year DFS: 77.8 vs. 55.0%, HR = 0.51, 95% CI 0.27–0.99, log-rank p = 0.048) and in TNBC patients (4-year DFS: 61.9 vs. 42.8%, HR = 0.49, 95% CI 0.24–1.02, log-rank p = 0.056), but not in luminal A-like.Conclusions: The chemotherapy for iLRR of breast cancer should be individualized for each patient, considering DFI, prior chemotherapy, and molecular subtypes.

The Impact of m6A RNA Modification in Therapy Resistance of Cancer: Implication in Chemotherapy, Radiotherapy, and Immunotherapy.

m6A RNA methylation, which serves as a critical regulator of transcript expression, has gathered tremendous scientific interest in recent years. From RNA processing to nuclear export, RNA translation to decay, m6A modification has been studied to affect various aspects of RNA metabolism, and it is now considered as one of the most abundant epitranscriptomic modification. RNA methyltransferases (writer), m6A-binding proteins (readers), and demethylases (erasers) proteins are frequently upregulated in several neoplasms, thereby regulating oncoprotein expression, augmenting tumor initiation, enhancing cancer cell proliferation, progression, and metastasis. Though the potential role of m6A methylation in growth and proliferation of cancer cells has been well documented, its potential role in development of therapy resistance in cancer is not clear. In this review, we focus on m6A-associated regulation, mechanisms, and functions in acquired chemoresistance, radioresistance, and resistance to immunotherapy in cancer.

Heart Failure and Malignancy: Implications of Chemotherapy and Radiation in the Pathogenesis of Cardiomyopathy in Cancer Treated Populations

The field of Cardio-oncology is rapidly growing with significant advances in research leading to better understanding of the underlying pathogenesis with implications in the diagnosis and management of cancer-related cardiomyopathy. Parallel to advancement in cardio-oncology is an increased awareness of the incidence of congestive heart failure and cardiomyopathy associated with malignancy. While specific cardiotoxic profiles exist for certain chemotherapeutic agents, there is increasing evidence of unexpected cardiotoxic side effects of some therapeutic modalities, combination chemo- and radiotherapy with large analyses identifying a strong association between malignancy and Takotsubo cardiomyopathy. Takotsubo Cardiomyopathy, also known as "broken-heart" syndrome or stress cardiomyopathy, is characterized by transient and reversible, regional or global, myocardial dysfunction without inciting ischemic perfusion defect from obstructive coronary artery disease. While direct causative pathophysiologic mechanisms continue to be investigated, much of the postulated pathways center on the high emotional and physical burdens of cancer and the related emotional stress associated with the diagnosis of cancer as well as the corporal effects of anti-neoplastic therapies, radiation, and oncologic surgery. In this manuscript we review the most current data in this rapidly emerging field highlighting the epidemiology, the postulated pathogenetic mechanisms as well as the current guidelines by major societies addressing malignancy -associated heart failure and cardiomyopathy, a rather complex disease entity with high morbidity and mortality.

Epigenetic Modulation of Self-Renewal Capacity of Leukemic Stem Cells and Implications for Chemotherapy.

Most patients with acute myeloid leukemia (AML) have a poor prognosis. Curative therapy of AML requires the complete eradication of the leukemic stem cells (LSCs). One aspect of LSCs that is poorly understood is their low frequency in the total population of leukemic cells in AML patients. After each cell division of LSCs, most of the daughter cells lose their capacity for self-renewal. Investigations into the role of Isocitrate dehydrogenase (IDH) mutations in AML provide some insight on the regulation of the proliferation of LSCs. The primary role of IDH is to convert isocitrate to alpha-keto-glutarate (α-KG). When IDH is mutated, it converts α-KG to 2-hydroxyglutarate (2-HG), an inhibitor of the TET pathway and Jumonji-C histone demethylases (JHDMs). The demethylating action of these enzymes removes the epigenetic gene-silencing markers, DNA methylation, H3K27me3 and H3K9me2 and can lead to the differentiation of LSCs. This enzymatic action is blocked by 2-HG in mutated IDH (mut-IDH) AML patients, who can be induced into remission with antagonists of 2-HG. These observations suggest that there exists in cells a natural enzymatic mechanism that uses demethylation to reverse epigenetic gene-silencing, leading to a loss of the self-renewal capacity of LSCs. This mechanism limits the proliferative potential of LSCs. Epigenetic agents that inhibit DNA and histone methylation exhibit a synergistic antineoplastic action on AML cells. It is possible that the therapeutic potential of this epigenetic therapy may be enhanced by demethylation enzymes, resulting in a very effective treatment for AML.

Chemotherapy and Inflammatory Cytokine Signalling in Cancer Cells and theTumour Microenvironment.

Cancer is the result of a cell's acquisition of a variety of biological capabilities or 'hallmarks' as outlined by Hanahan and Weinberg. These include sustained proliferative signalling, the ability to evade growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and the ability to invade other tissue and metastasize. More recently, the ability to escape immune destruction has been recognized as another important hallmark of tumours. It is suggested that genome instability and inflammation accelerates the acquisition of a variety of the above hallmarks. Inflammation, is a product of the body's response to tissue damage or pathogen invasion. It is required for tissue repair and host defense, but prolonged inflammation can often be the cause for disease. In a cancer patient, it is often unclear whether inflammation plays a protective or deleterious role in disease progression. Chemotherapy drugs can suppress tumour growth but also induce pathways in tumour cells that have been shown experimentally to support tumour progression or, in other cases, encourage an anti-tumour immune response. Thus, with the goal of better understanding the context under which each of these possible outcomes occurs, recent progress exploring chemotherapy-induced inflammatory cytokine production and the effects of cytokines on drug efficacy in the tumour microenvironment will be reviewed. The implications of chemotherapy on host and tumour cytokine pathways and their effect on the treatment of cancer patients will also be discussed.

Chemotherapy-related cognitive impairment or «chemobrain»: concept and state of art.

Cognitive complaints are frequent in patients who received chemotherapy for a non-CNS cancer. These observations have been described as «chemobrain». However, studies results are contradictory concerning the implication of chemotherapy in the onset of cognitive defects. Moreover, other factors as mood, anxiety and fatigue are often associated in this population and could be confounding. This article present principal results of research in human experiencing chemobrain, concerning clinical presentation, neuropsychological examination, imaging techniques and treatment possibilities. Physiopathological hypothesis are presented. The implication of hormonotherapy is also discussed.

Influence of TS and ABCB1gene polymorphisms on survival outcomes of 5‑FU-based chemotherapy in aChinese population of advanced gastric cancer patients.

To investigate the impacts of gene variations on survival outcomes of advanced gastric cancer (AGC) patients treated with 5‑fluorouracil (5-FU)-based chemotherapy, we analyzed the associations of 2 indels of the TS gene rs34743033 (double or triple tandem repeats of a28 bp sequence in 5'-UTR, denoted as 2R or 3R allele) and rs16430 (a6 bp variation at 1494 bp in 3'-UTR, denoted as ins6 or del6allele) and 2 single nucleotide polymorphisms (SNPs) of ABCB1gene rs2032582 in exon21 and rs1045642 in exon26, with clinical outcomes after 5‑FU treatment. Generally, indels rs34743033 and rs16430 were genotyped by PCR and polyacrylamide gel electrophoresis assay and SNPs rs2032582 and rs1045642 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 110Chinese AGC patients post-chemotherapy. Cox regression analysis was used to analyze the risk factors affecting patient survival. As aresult, rs34743033, rs1045642 and rs2032582 were shown to be significantly associated with overall survival (P< 0.05), and associations between the four polymorphisms with disease-free survival were also observed (P< 0.05). Moreover, we found that genotypes rs34743033 3R/2R, rs16430 ins6/del6, rs1045642 CC or CT, and rs2032582GG were beneficial predictors of clinical treatment outcome in AGC patients, suggesting some clinical implications in chemotherapy of aChinese population.

Abstract 3410: Downregulation of let 7a 5p predicts lymph node metastasis and prognosis in colorectal cancer: implications for chemotherapy

Abstract Background. Colorectal cancer guidelines recommend adjuvant chemotherapy is based on the number of lymph nodes metastasis. Let-7a-5p is a microRNA which could inhibits migration, invasion and epithelial-mesenchymal transition by targeting HMGA2. The aim of this study was to investigate the role of let-7a-5p in clinical impact of colorectal cancer (CRC). Methods. One hundred ninety-two CRC patients were enrolled. The expression of let-7a-5p and HMGA2 in serums and tumor tissues were analyzed by real-time PCR and immunohistochemistry. Univariate (Kaplan-Meier) analysis was used to analyze primary outcomes included 5-year overall survival and tumor recurrence. Results. The expression of let-7a-5p in tumor tissues was significantly negative correlated with tumor size, stage, and lymph node metastasis in CRC patients (p = 0.024 for tumor size, p = &amp;lt;0.0001 for stage, and p&amp;lt;0.0001 for lymph node metastasis). There was a negative correlation between levels of let-7a-5p and the HMGA2 gene (p &amp;lt;0.0001), especially in CRC patients with wildtype APC gene. Patients with let-7a-5p low / HMGA2 high had poorer overall survival (OS) and disease-free survival (DFS) rates than those with let-7a-5p high / HMGA2 high, let-7a-5p high / HMGA2 low, and let-7a-5p low /HMGA2 low groups. In addition, the expression levels of let-7a-5p in PBMCs were positive correlated with in tumor tissues of CRC patients. Conclusion. We suggest that down-regulation of let-7a-5p in PBMCs and tumor tissues patients could be used to predicts lymph node metastasis and prognosis impact on chemotherapy of colorectal cancer Citation Format: Ya-Wen Cheng, Tsang-Pai Liu, Po-Li Wei, Huei Lee. Downregulation of let 7a 5p predicts lymph node metastasis and prognosis in colorectal cancer: implications for chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3410.

Assessment of insulin-like growth factor 1 receptor as an oncogene in esophageal squamous cell carcinoma and its potential implication in chemotherapy.

Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of multiple cancers. After ligand binding, IGF-1R can initiate the activation of the PI3K/AKT/mTOR and Ras/Raf/MEK/MAPK pathways to modulate cell proliferation, survival, differentiation, motility, invasion and angiogenesis. IGF-1R is a prerequisite for tumor progression and is one of the most attractive targets for therapeutic interventions in several types of cancer. In the present study, we determined the expression of IGF-1R in an esophageal squamous cell carcinoma(ESCC) cohort, investigated the detailed function of IGF-1R and screened the potential application of IGF-1R in the clinic. We verified the higher expression of IGF-1R in ESCC tumor tissues as compared to adjacent normal tissues. We also found that high expression of IGF-1R was associated with advanced tumor progression. We used ESCC cell lines and a mouse xenograft model to detect the function of IGF-1R invitro and invivo. Our results suggest the oncogenic function of IGF-1R in regulating cell proliferation, clonogenesis, the cell cycle and apoptosis. In addition, we found that IGF-1R was associated with the response to standard chemotherapy drugs 5-FU and cisplatin in an ESCC cell line. More importantly, we confirmed that the serum concentration of IGF-1/IGFBP3 can be used for predicting response to chemotherapy, and increased serum levels of IGF-1 and IGFBP-3 are associated with significantly higher rates of tumor response. In the present study, we demonstrated that IGF-1R is an important oncogene in ESCC and can be used to detect the chemotherapeutic response.

Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy

The putative tumour suppressor and apoptosis-promoting gene, growth arrest-specific 5 (GAS5), encodes long ncRNA (lncRNA) and snoRNAs. Its expression is down-regulated in breast cancer, which adversely impacts patient prognosis. In this preclinical study, the consequences of decreased GAS5 expression for breast cancer cell survival following treatment with chemotherapeutic agents are addressed. In addition, functional responses of triple-negative breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to enhance cellular GAS5 levels is investigated. Breast cancer cell lines were transfected with either siRNA to GAS5 or with a plasmid encoding GAS5 lncRNA and the effects on breast cancer cell survival were determined. Cellular responses to mTOR inhibitors were evaluated by assaying culture growth and GAS5 transcript levels. GAS5 silencing attenuated cell responses to apoptotic stimuli, including classical chemotherapeutic agents; the extent of cell death was directly proportional to cellular GAS5 levels. Imatinib action in contrast, was independent of GAS5. GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. Reduced GAS5 expression attenuates apoptosis induction by classical chemotherapeutic agents in breast cancer cells, providing an explanation for the relationship between GAS5 expression and breast cancer patient prognosis. Clinically, this relationship may be circumvented by the use of GAS5-independent drugs such as imatinib, or by restoration of GAS5 expression. The latter may be achieved by the use of a dual PI3K/mTOR inhibitor, to improve apoptotic responses to conventional chemotherapies.

Patterns of resource utilization and cost for postmenopausal women with hormone-receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) in Europe.

e17520 Background: Healthcare resource utilization varies by disease stage and treatment choice. Notably, chemotherapy (CT) use is associated with extensive healthcare resource utilization and cost. This study reviews the direct and indirect cost implications of CT versus hormonal therapy (HT) in the ABC setting through the first 3 lines of treatment. Methods: A retrospective chart review of postmenopausal women diagnosed with HR+, HER2– ABC in 5 European countries was conducted. Patients must have progressed on at least 1 line of HT and completed at least 1 line of CT in the ABC setting. Patient cohorts based on therapy received in each line were constructed (cohort A: HT 1st-line, CT 2nd-line, and any treatment 3rd-line; cohort B: HT 1st- and 2nd-line with CT 3rd-line; and cohort C: CT 1st-line with any 2nd- and 3rd-line). Costs of care based on resource utilization and country-specific cost were calculated by patient cohort and line of therapy. Working status was also assessed. Results: A total of 355 eligible patient charts between 2008 and 2012 were included in the analysis: cohort A, 218 (61%) patients; cohort B, 26 (7%) patients; and cohort C 111 (31%) patients. Total direct costs over all 3 treatment lines were €14,362 higher for CT versus HT as 1st-line therapy (cohort C vs A) and €10,368 higher for CT versus HT as 2nd-line (cohort A vs B). Monthly direct costs were €2,536 higher for CT versus HT for 1st-line therapy and €1,713 higher for CT versus HT in 2nd-line. Increased costs for CT were due to treatments to manage side effects, use of concomitant targeted therapies, and increased frequency of hospitalizations, healthcare provider visits, and monitoring tests. On switching from HT to CT, there was a doubling of the proportion of patients on sick leaves in both cohorts A and B. Conclusions: These results suggest an increased direct cost of care for CT relative to HT in European postmenopausal women with HR+, HER2– ABC. Furthermore, CT-based therapy appears to be associated with lower productivity of working-age patients, potentially increasing overall indirect costs.

Glycogen Synthase Kinase 3β in Pancreatic Cancer and its Implications in Chemotherapy and Radiation Therapy.

Pancreatic cancer is a highly lethal disease with a poor prognosis characterized by local and systemic disease progression. Both radiation and chemotherapy play important roles in the management of this disease. However, in order to improve standard therapy many molecularly targeted agents are being developed. Glycogen synthase kinase 3β (GSK3β) participates in a multitude of cellular processes and is a newly proposed therapeutic target in pancreatic cancer. This review will discuss both the oncogenic and tumor suppressor functions of GSK3β in pancreatic cancer with an emphasis on the roles of GSK3β in tumor cell survival and sensitivity to radiation and chemotherapy.

Polyamines and cancer: implications for chemotherapy and chemoprevention

Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes, and a poorly characterised transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate and skin cancers, and altered levels of rate-limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway-specific drugs and ongoing clinical trials targeting polyamine biosynthesis.