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Immune checkpoint therapy (ICB) has conferred significant and durable clinical benefit to some patients with cancer. However, most patients do not respond to ICB, and reliable biomarkers of ICB response are needed to improve patient stratification. Here, we performed a transcriptome-wide meta-analysis across 1,486 tumors from ICB-treated patients and tumors with expected ICB outcomes based on microsatellite status. Using a robust transcriptome deconvolution approach, we inferred cancer- and stroma-specific gene expression differences and identified cell-type specific features of ICB response across cancer types. Consistent with current knowledge, stromal expression of CXCL9, CXCL13, and IFNG were the top determinants of favorable ICB response. In addition, we identified a group of potential immune-suppressive genes, including FCER1A, associated with poor response to ICB. Strikingly, PD-L1 expression in stromal cells, but not cancer cells, is correlated with ICB response across cancer types. Furthermore, the unbiased transcriptome-wide analysis failed to identify cancer-cell intrinsic expression signatures of ICB response conserved across tumor types, suggesting that cancer cells lack tissue-agnostic transcriptomic features of ICB response., Significance: Our results challenge the prevailing dogma that cancer cells present tissue-agnostic molecular markers that modulate immune activity and ICB response, which has implications on the development of improved ICB diagnostics and treatments., (© 2024 The Authors; Published by the American Association for Cancer Research.)

For three years, COVID-19 has circulated among our communities and around the world, fundamentally changing social interactions, health care systems, and service delivery. For people living with (and receiving treatment for) cancer, pandemic conditions presented significant additional hurdles in an already unstable and shifting environment, including disrupted personal contact with care providers, interrupted access to clinical trials, distanced therapeutic encounters, multiple immune vulnerabilities, and new forms of financial precarity. In a 2020 perspective in this journal, we examined how COVID-19 was reshaping cancer care in the early stages of the pandemic and how these changes might endure into the future. Three years later, and in light of a series of interviews with patients and their caregivers from the United States and Australia conducted during the pandemic, we return to consider the potential legacy effects of the pandemic on cancer care. While some challenges to care provision and survivorship were unforeseen, others accentuated and amplified existing problems experienced by patients, caregivers, and health care providers. Both are likely to have enduring effects in the "post-pandemic" world, raising the importance of focusing on lessons that can be learned for the future., (©2023 The Authors; Published by the American Association for Cancer Research.)

Clinical trials that have a pharmacokinetic or a pharmacodynamic immunologic mechanism of action-based primary outcome could substantially improve the validity and efficiency of early development of immuno-oncology agents. Here, we outline different trial design options in this area, review examples from the literature and their unique immunologic aspects, and highlight how these trials have been underutilized. We illustrate how new technologies and translationally focused approaches can be successfully used to develop different classes of immunotherapeutic agents., (©2021 The Authors; Published by the American Association for Cancer Research.)

With rapid advances in our understanding of cancer, there is an expanding number of potential novel combination therapies, including novel-novel combinations. Identifying which combinations are appropriate and in which subpopulations are among the most difficult questions in medical research. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review of trials of novel-novel combination therapies involving immunotherapies or molecular targeted therapies in advanced solid tumors. A MEDLINE search was conducted using a modified Cochrane Highly Sensitive Search Strategy for published clinical trials between July 1, 2017, and June 30, 2020, in the top-ranked medical and oncology journals. Trials were evaluated according to a criterion adapted from previously published Food and Drug Administration guidance and other key considerations in designing trials of combinations. This included the presence of a strong biological rationale, the use of a new established or emerging predictive biomarker prospectively incorporated into the clinical trial design, appropriate comparator arms of monotherapy or supportive external data sources and a primary endpoint demonstrating a clinically meaningful benefit. Of 32 identified trials, there were 11 (34%) trials of the novel-novel combination of anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) therapy, and 10 (31%) trials of anti-PD-1/PD-L1 and anti-vascular endothelial growth factor (VEGF) combination therapy. 20 (62.5%) trials were phase II trials, while 12 (37.5%) were phase III trials. Most (72%) trials lacked significant preclinical evidence supporting the development of the combination in the given indication. A majority of trials (69%) were conducted in biomarker unselected populations or used pre-existing biomarkers within the given indication for patient selection. Most studies (66%) were considered to have appropriate comparator arms or had supportive external data sources such as prior studies of monotherapy. All studies were evaluated as selecting a clinically meaningful primary endpoint. In conclusion, designing trials to evaluate novel-novel combination therapies presents numerous challenges to demonstrate efficacy in a comprehensive manner. A greater understanding of biological rationale for combinations and incorporating predictive biomarkers may improve effective evaluation of combination therapies. Innovative statistical methods and increasing use of external data to support combination approaches are potential strategies that may improve the efficiency of trial design. Designing trials to evaluate novel-novel combination therapies presents numerous challenges to demonstrate efficacy in a comprehensive manner. A greater understanding of biological rationale for combinations and incorporating predictive biomarkers may improve effective evaluation of combination therapies. Innovative statistical methods and increasing use of external data to support combination approaches are potential strategies that may improve the efficiency of trial design., Competing Interests: Competing interests: ACT reports consultant or advisory roles for Amgen. SJB reports research grants from Incyte, Eli Lilly, Novocure, GSK; consultant or advisory roles for Bayer and Novocure; and US patent for 'Combination therapies of EGFRvIII chimeric antigen receptors and PD-1 inhibitors'. PYW reports consultant or advisory roles for Agios, Astra Zeneca, Bayer, Boston Pharmaceuticals, CNS Pharmaceuticals, Elevate Bio Immunomic Therapeutics, Imvax, Karyopharm, Merck, Novartis, Nuvation Bio, Vascular Biogenics, VBI Vaccines, Voyager and QED; research funding from Agios, Astra Zeneca/Medimmune, Beigene, Celgene, Eli Lily, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Oncoceutics, Vascular Biogenics and VBI Vaccines; is an editor for UpToDate and Elsevier. ML reports consultant or advisory roles for Tocagen, SQZ Technologies, VBI, InCephalo Therapeutics and Pyramid Bio; non-research consulting roles for Stryker; research support from Arbor, Bristol-Myers Squibb, Accuray, DNAtrix, Tocagen, Biohaven and Kyrin-Kyowa; and has patents for focused radiation+checkpoint inhibitors and local chemotherapy+checkpoint inhibitors. MP reports consultant or advisory roles for non-financial support from Roche, personal fees and non-financial support from Bayer, personal fees from Novartis, personal fees from Apogenix, non-financial support from Pfizer, personal fees from Affiris outside the submitted work. In addition, MP has a patent EP2753315B1 licensed to Bayer, a patent EP2800580B1 issued, a patent US20180155403A1 pending, a patent US20180246118A1 pending, a patent US20170254803A1 pending, a patent WO2018146010A1 licensed to Bayer, a patent WO2019101643A1 licensed to Bayer, a patent WO2019101647A1 licensed to Bayer, a patent WO2019101641A1 licensed to Bayer, and a patent WO2019101642A1 licensed to Bayer. HC reports consultant or advisory roles for Best Doctors/Teladoc, Karyopharm Therapeutics, Private Health, Orbus, Bayer, Forma Therapeutics and Adastra Pharmaceuticals; research funding (Inst) from Newlink Genetics, Plexxikon, Kadmon, Orbus, Merck, DNATrix, Abbvie, Beigene, Forma Therapeutics, GCAR, Array BioPharma, Karyopharm, Nuvation Bio, Bayer and Bristol Meyer Squibb. DMA reports stock and other ownership interests in Diverse Biotech; consulting or advisory roles for Istari Oncology and Jackson Laboratory for Genomic Medicine; patents, royalties, other intellectual property for 'Methods for predicting tumor response to immunotherapy, U.S. Provisional application no. 62/787' and 'Methods for predicting tumor response to immunotherapy, U.S. Provisional application no. 62/620,577'; and expert testimony for Tanoury, Nauts, McKinney & Gabarino, PLLC. WW reports consultant or advisory roles (Inst) for Agios, Bayer, MSD, Novartis and Roche; research funding (Inst) from Apogenix, Boehringer Ingelheim, Pfizer and Roche. SMC reports research funding (Inst) from Agios. EG reports consultant or advisory roles (Inst) for MedImmune, Inc., Agios Pharmaceuticals and Karyopharm; consultant or advisory roles for Gradalis, Inc. and Kiyatec, Inc.; research funding (Inst) from MedImmune, Inc., Tracon, Genentech and Bristol-Myers Squibb. MPM reports consultant or advisory roles for Zap, Mevion, Karyopharm, Tocagen and Astra-Zeneca; and Board of Directors options from Oncoceutics. ABH reports consultant or advisory roles for Caris Life Sciences and WCG Oncology; royalties on licensed intellectual property from Celldex Therapeutics and DNAtrix; research funding from Celularity, Carthera, Codiak, and Moleculin. DAR reports consultant or advisory roles for Abbvie, Advantagene, Agenus, Amgen, Bayer, Bristol-Myers Squibb, Celldex, DelMar, EMD Serono, Genentech/Roche, Imvax, Inovio, Medicenna Biopharma, Inc., Merck, Merck KGaA, Monteris, Novocure, Oncorus, Oxigene, Regeneron, Stemline, Sumitono Dainippon Pharma and Taiho Oncology, Inc.; honoraria from Abbvie, Advantagene, Agenus, Bristol-Myers Squibb, Celldex, EMD Serono, Genentech/Roche, Imvax, Inovio, Medicenna Biopharma, Inc., Merck, Merck KGaA, Monteris, Novocure, Oncorus, Oxigene, Regeneron, Stemline, Sumitono Dainippon Pharma and Taiho Oncology, Inc.; research funding (Inst) from Acerta Phamaceuticals, Agenus, Celldex, EMD Serono, Incyte, Inovio, Omniox and Tragara. SS reports consultant or advisory roles for Merck and Boehringer Ingelheim; research funding from Merck, Bristol-Myers Squibb, and Brooklyn ImmunoTherapeutics. RJS reports research funding (Inst) from Bayer, Astra Zeneca, Pfizer, Astella, Roche, Merck, Abbvie and Amgen. SJA reports consultant or advisory roles for Achilles, Amgen, AstraZeneca, Bristol-Myers Squibb, Caris Life Sciences, CBMG, Celsius Therapeutics, G1 Therapeutics, GlaxoSmithKline, Memgen, Merck, Nektar, RAPT Therapeutics, Venn, Glympse and Samyang; data review committee for EMD Serano. DB is co-owner of Berry Consultants, LLC, a company that designs adaptive Bayesian clinical trials for pharmaceutical and medical device companies, NIH cooperative groups, patient advocacy groups, and international consortia. MK reports consultant or advisory roles for Janssen, AbbVie, Ipsen, Pfizer Roche, and Jackson Laboratory for Genomic Medicine; research funding from AbbVie, Bristol-Myers Squibb, and Specialized Therapeutics. AM, SK and VKP report no conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center., Patients and Methods: Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore. Primary objective was to identify molecular biomarkers in patient's tumors for allocation to clinical trials. The study commenced in February 2012 and is ongoing, with the results of all patients who underwent multiplex next-generation sequencing (NGS) testing until December 2018 presented here. The results were discussed at a molecular tumor board where recommendations for allocation to biomarker-directed trials or targeted therapies were made., Results: One thousand fifteen patients were enrolled with a median age of 58 years (range 20-83 years). Most common tumor types were lung adenocarcinoma (26%), colorectal cancer (15%), and breast cancer (12%). A total of 1,064 NGS assays were performed, on fresh tumor tissue for 369 (35%) and archival tumor tissue for 687 (65%) assays. TP53 (39%) alterations were most common, followed by EGFR (21%), KRAS (14%), and PIK3CA (10%). Of 405 NGS assays with potentially actionable alterations, 111 (27%) were allocated to a clinical trial after molecular tumor board and 20 (4.9%) were enrolled on a molecularly matched clinical trial. Gene fusions were detected in 23 of 311 (7%) patients tested, including rare fusions in new tumor types and known fusions in rare tumors., Conclusion: Individualized Molecular Profiling for Allocation to Clinical Trials Singapore demonstrates the feasibility of a prospective broad molecular profiling program in an Asian tertiary cancer center, with the ability to develop and adapt to a dynamic landscape of precision oncology., Competing Interests: Aaron C. Tan Honoraria: Amgen, Thermo Fisher Scientific Travel, Accommodations, Expenses: ASLAN Pharmaceuticals, Illumina Tira J. Tan Stock and Other Ownership Interests: Immunomedics Honoraria: AstraZeneca, Roche/Genentech Consulting or Advisory Role: AstraZeneca, Lilly, Pfizer, DKSH, Novartis Speakers' Bureau: Novartis Research Funding: Bayer, Novartis, AstraZeneca, Odonate Therapeutics, Synthon Travel, Accommodations, Expenses: AstraZeneca, Eisai Matthew C. H. Ng Honoraria: MSD Oncology, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Lilly Consulting or Advisory Role: MSD Oncology, Bristol Myers Squibb, Novartis, Merck Speakers' Bureau: Lilly Research Funding: ASLAN Pharmaceuticals Travel, Accommodations, Expenses: MSD Oncology, Taiho Pharmaceutical, Bristol Myers Squibb David W. M. Tai Honoraria: Bristol Myers Squibb, Eisai Consulting or Advisory Role: Bristol Myers Squibb, Eisai Speakers' Bureau: Ipsen, Bristol Myers Squibb, Eisai, Roche Research Funding: Bristol-Myers Squibb, Sirtex Medical, Novartis. Justina Y. C. Lam Honoraria: AstraZeneca Consulting or Advisory Role: AstraZeneca Research Funding: Bayer, Merus, Bristol Myers Squibb Travel, Accommodations, Expenses: Lilly Bien-Soo Tan Research Funding: Boston Scientific Rebecca Alexandra Dent Honoraria: Roche/Genentech, AstraZeneca, Pfizer, MSD Consulting or Advisory Role: Roche, Pfizer, Merck, Eisai, AstraZeneca, Novartis Travel, Accommodations, Expenses: Roche, Pfizer, Amgen, Merck Yoon-Sim Yap Honoraria: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Consulting or Advisory Role: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Travel, Accommodations, Expenses: Pfizer, AstraZeneca, Eisai, Lilly, Roche, Novartis Iain B. H. Tan Honoraria: Amgen, Roche, Merck Serono, MSD Consulting or Advisory Role: Amgen, Roche, Merck Serono, MSD, Novartis Research Funding: MSD Travel, Accommodations, Expenses: Merck Serono, Amgen Su Pin Choo Honoraria: Bristol Myers Squibb, AstraZeneca Consulting or Advisory Role: Bristol Myers Squibb, AstraZeneca, Bayer, MSD Oncology, Eisai, Roche Travel, Accommodations, Expenses: Taiho Pharmaceutical, Bristol Myers Squibb Chee-Keong Toh Stock and Other Ownership Interests: Nektar Consulting or Advisory Role: Merck, Bristol Myers Squibb/Celgene, Astellas Pharma, MSD Oncology, Roche, DKSH, Natera, Eisai, Pfizer Speakers' Bureau: Ipsen, AstraZeneca, Merck, Astellas Pharma Mohamad Farid Honoraria: Bayer Consulting or Advisory Role: Bayer N. Gopalakrishna Iyer Consulting or Advisory Role: InvitroCue Patents, Royalties, Other Intellectual Property: A device and method of providing lighting during surgeries in deep and narrow cavities Inventors: N. C. Tan, W. S. Tan, M. H. Chew, H. K. Tan, P. Sunkeri, R. S. L. Lieu, F. W. L. Loke, N. G. Iyer. PCTSG2016-050231. Licensed to Vivo Surgical Pte Ltd Wan Teck Lim Consulting or Advisory Role: Roche, AstraZeneca, MSD Oncology, Novartis, Boehringer Ingelheim Research Funding: Bristol Myers Squibb Travel, Accommodations, Expenses: AstraZeneca, Taiho Pharmaceutical Daniel S. W. Tan Honoraria: Bristol Myers Squibb, Takeda, Novartis, Roche, Pfizer Consulting or Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer Research Funding: Novartis, GlaxoSmithKline, AstraZeneca Travel, Accommodations, Expenses: Pfizer, Boehringer Ingelheim, Roche No other potential conflicts of interest were reported.Aaron C. Tan Honoraria: Amgen, Thermo Fisher Scientific Travel, Accommodations, Expenses: ASLAN Pharmaceuticals, Illumina Tira J. Tan Stock and Other Ownership Interests: Immunomedics Honoraria: AstraZeneca, Roche/Genentech Consulting or Advisory Role: AstraZeneca, Lilly, Pfizer, DKSH, Novartis Speakers' Bureau: Novartis Research Funding: Bayer, Novartis, AstraZeneca, Odonate Therapeutics, Synthon Travel, Accommodations, Expenses: AstraZeneca, Eisai Matthew C. H. Ng Honoraria: MSD Oncology, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Lilly Consulting or Advisory Role: MSD Oncology, Bristol Myers Squibb, Novartis, Merck Speakers' Bureau: Lilly Research Funding: ASLAN Pharmaceuticals Travel, Accommodations, Expenses: MSD Oncology, Taiho Pharmaceutical, Bristol Myers Squibb David W. M. Tai Honoraria: Bristol Myers Squibb, Eisai Consulting or Advisory Role: Bristol Myers Squibb, Eisai Speakers' Bureau: Ipsen, Bristol Myers Squibb, Eisai, Roche Research Funding: Bristol-Myers Squibb, Sirtex Medical, Novartis. Justina Y. C. Lam Honoraria: AstraZeneca Consulting or Advisory Role: AstraZeneca Research Funding: Bayer, Merus, Bristol Myers Squibb Travel, Accommodations, Expenses: Lilly Bien-Soo Tan Research Funding: Boston Scientific Rebecca Alexandra Dent Honoraria: Roche/Genentech, AstraZeneca, Pfizer, MSD Consulting or Advisory Role: Roche, Pfizer, Merck, Eisai, AstraZeneca, Novartis Travel, Accommodations, Expenses: Roche, Pfizer, Amgen, Merck Yoon-Sim Yap Honoraria: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Consulting or Advisory Role: Novartis, Lilly, Pfizer, AstraZeneca, Eisai, MSD, Inivata Travel, Accommodations, Expenses: Pfizer, AstraZeneca, Eisai, Lilly, Roche, Novartis Iain B. H. Tan Honoraria: Amgen, Roche, Merck Serono, MSD Consulting or Advisory Role: Amgen, Roche, Merck Serono, MSD, Novartis Research Funding: MSD Travel, Accommodations, Expenses: Merck Serono, Amgen Su Pin Choo Honoraria: Bristol Myers Squibb, AstraZeneca Consulting or Advisory Role: Bristol Myers Squibb, AstraZeneca, Bayer, MSD Oncology, Eisai, Roche Travel, Accommodations, Expenses: Taiho Pharmaceutical, Bristol Myers Squibb Chee-Keong Toh Stock and Other Ownership Interests: Nektar Consulting or Advisory Role: Merck, Bristol Myers Squibb/Celgene, Astellas Pharma, MSD Oncology, Roche, DKSH, Natera, Eisai, Pfizer Speakers' Bureau: Ipsen, AstraZeneca, Merck, Astellas Pharma Mohamad Farid Honoraria: Bayer Consulting or Advisory Role: Bayer N. Gopalakrishna Iyer Consulting or Advisory Role: InvitroCue Patents, Royalties, Other Intellectual Property: A device and method of providing lighting during surgeries in deep and narrow cavities Inventors: N. C. Tan, W. S. Tan, M. H. Chew, H. K. Tan, P. Sunkeri, R. S. L. Lieu, F. W. L. Loke, N. G. Iyer. PCTSG2016-050231. Licensed to Vivo Surgical Pte Ltd Wan Teck Lim Consulting or Advisory Role: Roche, AstraZeneca, MSD Oncology, Novartis, Boehringer Ingelheim Research Funding: Bristol Myers Squibb Travel, Accommodations, Expenses: AstraZeneca, Taiho Pharmaceutical Daniel S. W. Tan Honoraria: Bristol Myers Squibb, Takeda, Novartis, Roche, Pfizer Consulting or Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer Research Funding: Novartis, GlaxoSmithKline, AstraZeneca Travel, Accommodations, Expenses: Pfizer, Boehringer Ingelheim, Roche No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

Coronavirus disease 2019 (COVID-19) has fundamentally disrupted the practice of oncology, shifting care onto virtual platforms, rearranging the logistics and economics of running a successful clinical practice and research, and in some contexts, redefining what treatments patients with cancer should and can receive. Since the start of the pandemic in early 2020, there has been considerable emphasis placed on the implications for patients with cancer in terms of their vulnerability to the virus and potential exposure in healthcare settings. But little emphasis has been placed on the significant, and potentially enduring, consequences of COVID-19 for how cancer care is delivered. In this article, we outline the importance of a focus on the effects of COVID-19 for oncology practice during and potentially after the pandemic, focusing on key shifts that are already evident, including: the pivot to online consultations, shifts in access to clinical trial and definitions of "essential care," the changing economics of practice, and the potential legacy effects of rapidly implemented changes in cancer care. COVID-19 is reshaping oncology practice, clinical trials, and delivery of cancer care broadly, and these changes might endure well beyond the short- to mid-term of the active pandemic. Therefore, shifts in practice brought about by the pandemic must be accompanied by improved training and awareness, enhanced infrastructure, and evidence-based support if they are to harness the positives and offset the potential negative consequences of the impacts of COVID-19 on cancer care., (©2020 American Association for Cancer Research.)

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has necessitated changes in cancer care delivery as resources are reallocated. Clinical trials and other research activities are inevitably impacted. Start-up activities for new trials may be deferred and recruitment suspended. For patients already enrolled however, there are challenges in continuing treatment on trial. Regulatory bodies have issued guidance on managing clinical trials during the pandemic, including contingency measures for remote study visits, delivery of investigational product, and site monitoring visits. New cancer clinical trial practices during the SARS-CoV-2 pandemic include new risk assessment strategies, decentralized and remote trial coordination, data collection, and delegation of specific therapeutic activities. This experience could provide evidence of more feasible and cost-effective methods for future clinical trial conduct., (©2020 American Association for Cancer Research.)

Background: Patients with advanced malignancies have historically been considered poor candidates for admission to the intensive care unit (ICU); however, prognosis is continually improving, and requirements for ICU access are increasing., Aim: To understand the characteristics and outcomes of oncology unit patients admitted to an Australian ICU and identify potential prognostic factors., Methods: A single-centre, retrospective, cohort study conducted at a tertiary public hospital with a quaternary ICU in Sydney, Australia. All patients admitted under the medical oncology team requiring ICU admission between June 2014 and June 2016 were evaluated. Clinical outcomes were determined including mortality, ICU requirements (ventilation, dialysis, vasopressors, infection) and prognostic scores (Acute Physiologic and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) score)., Results: There were 96 patients with mean age 61 years, 58% were male and 76% had metastatic disease. Most were receiving palliative treatment (89%), with recent chemotherapy (43%), immunotherapy (10%) and other therapies (5%). Of the 10 patients with recent immunotherapy, three (all with melanoma) required ICU admission due to immunotoxicity; 13% were admitted due to an oncological emergency. Mean APACHE II score was 17 (standard deviation (SD) 5.33), mean SOFA score was 3.99 (SD 2.70), ICU mortality was 5% and hospital mortality was 22%. Using multivariate logistic regression analysis, cancer stage, infection during ICU admission, intracranial mass effect on ICU admission and SOFA score were associated with 30-day mortality., Conclusion: Our patient population had good short-term survival outcomes despite most receiving palliative treatment. Cancer patients can achieve positive outcomes after ICU admission, and appropriate selection of patients is crucial., (© 2018 Royal Australasian College of Physicians.)

Stimuli-responsive nanoprobes that combine both fluorescence and magnetic resonance imaging (MRI) are anticipated to be highly beneficial for tumor visualization with high imaging sensitivity. By employing an interfacial templating scheme, a pH-activatable fluorescence/MRI dual-modality imaging nanoprobe is successfully developed based on the coencapsulation of MnO nanoparticles and coumarin-545T inside a hybrid silica nanoshell. To promote cancer cell targeting with high-specificity, the nanoprobes are also conjugated with folic acid to establish a greater affinity for cancer cells that over-express folate receptors on their cell membrane. In the new nanosystem, MnO nanoparticles are shown to function as an efficient fluorescence quencher of coumarin-545T prior to cellular uptake. However, fluorescence recovery is achieved upon acidic dissolution of the MnO nanoparticles following receptor-mediated endocytosis into the low pH compartments of the cancer cells. Meanwhile, the Mn(2+) ions thus released are also shown to exert a strong T1 contrast enhancement in the cancer cells. Therefore, by demonstrating the dual-activatable MRI and fluorescence imaging in response to the low pH conditions, it is envisioned that these nanoprobes would have tremendous potential for emerging cancer-imaging modalities such as image-guided cancer therapy., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nanotechnology has been widely used in the development of new strategies for drug delivery and cancer therapy. Compared to traditional drug delivery systems, nano-based drug delivery system have greater potential in a variety of areas, such as multiple targeting functionalization, in vivo imaging, combined drug delivery, extended circulation time, and systemic control release. Nano-systems incorporating stimulus-responsive materials have remarkable properties which allow them to bypass biological barriers and achieve targeted intracellular drug delivery. As a result of the active metabolism of tumor cells, the tumor microenvironment (TME) is highly acidic compared to normal tissues. pH-Sensitive nano-systems have now been developed in which drug release is specifically triggered by the acidic tumor environment. Studies have demonstrated that novel pH-sensitive drug delivery systems are capable of improving the efficiency of cancer treatment. A number of these have been translated from bench to clinical application and have been approved by the Food and Drug Administration (FDA) for treatment of various cancerous diseases. Herein, this review mainly focuses on pH-sensitive nano-systems, including advances in drug delivery, mechanisms of drug release, and possible improvements in drug absorption, with the emphasis on recent research in this field. With deeper understanding of the difference between normal and tumor tissues, it might be possible to design ever more promising pH-responsive nano-systems for drug delivery and cancer therapy in the near future., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Interest in dietary phytochemicals for potential cancer chemoprevention has increased substantially. Screening dietary compounds for chemopreventive activity however, requires a systematic and wide-ranging approach to encompass the complexity of carcinogenesis. We present some of the molecular pathways that underpin the broad biological processes involved in carcinogenesis. Oxidative stress, inflammation, and the evasion of apoptosis are important biological mechanisms by which carcinogenesis occurs. Subsequently, antioxidant, anti-inflammatory, and pro-apoptotic activity represent important activities for preventing, suppressing, or reversing the development of carcinogenesis. Ultimately, these mechanisms of action may provide a useful basis for screening novel phytochemicals for chemopreventive activity. In this review, we identify the important molecular processes that may be targeted in routine screenings of dietary phytochemicals to ultimately select the most effective potential candidates for cancer chemoprevention.