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Background It has been suggested that the results from fragile trials are less likely to translate into benefit in routine clinical practice. Methods We searched the Food and Drug Administration (FDA) archives to identify drug approvals for solid organ malignancies between 2010 and 2019. We calculated the Fragility Index (FI) supporting each approval, using methods to account for time‐to‐event. We compared FI and trial and approval characteristics using Mann‐Whitney U and Kruskal‐Wallis test. Using logistic regression, we examined study characteristics associated with withdrawal of consent or lost to follow‐up (WCLFU) exceeding the calculated FI. Results The median FI among 125 included studies was 23 (range 1–322). The FI was ≤10 in 35 studies (28%), 11–20 in 21 (17%), and >20 in 69 (55%). The median FI/Nexp was 7.7% (range 0.1–51.7%). The median FI was significantly lower among approvals processed through the accelerated vs regular pathway (5.5 vs 25, p = 0.001), but there was no difference in median FI/Nexp. The WCLFU exceeded FI in 42% of studies. Overall survival endpoints were more likely to have a WCLFU exceeding FI (OR 3.16, p = 0.003). WCLFU exceeding FI was also associated with a lesser magnitude of effect (median HR 0.69 vs 0.55, p FI. Conclusion The median FI among all trials was 23, and WCLFU exceeded FI in 42%. Comparative trials in solid tumors supporting approval through the accelerated pathway are more fragile compared to trials approved through the regular pathway, an observation likely explained by a lower sample size in the experimental arm., Trials in solid tumors supporting accelerated approval are more fragile compared to regular approvals. This finding supports the need for post‐marketing trials or real‐world analyses to ensure the benefit observed in clinical trials is robust and reproducible.

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long-term follow-up strategies for patients at risk of cancer therapy-related cardiotoxicities. Research to better define strategies for early identification, follow-up and management is highly necessary. Although the academic cardio-oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross-discipline interactions and help in the design and funding of cardio-oncology trials. The overarching goals of cardio-oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology.

The thioredoxin system is highly conserved system found in all living cells and comprises NADPH, thioredoxin, and thioredoxin reductase. This system plays a critical role in preserving a reduced intracellular environment, and its involvement in regulating a wide range of cellular functions makes it especially vital to cellular homeostasis. Its critical role is not limited to healthy cells, it is also involved in cancer development, and is overexpressed in many cancers. This makes the thioredoxin system a promising target for cancer drug development. As such, over the last decade, many inhibitors have been developed that target the thioredoxin system, most of which are small molecules targeting the thioredoxin reductase C-terminal redox center. A few inhibitors of thioredoxin have also been developed. We believe that more efforts should be invested in developing protein/peptide-based inhibitors against both thioredoxin reductase and/or thioredoxin.

Growth factor receptors are known to be involved in the process of viral infection. Many viruses not only use growth factor receptors to physically attach to the cell surface and internalize, but also divert receptor tyrosine kinase signaling in order to replicate. Thus, repurposing drugs that have initially been developed to target growth factor receptors and their signaling in cancer may prove to be a fast track to effective therapies against emerging new viral infections, including the coronavirus disease 19 (COVID‐19).

As high-throughput sequencing experiments become more widely used in pre-clinical and clinical settings, pharmacogenetic and pharmacogenomic biomarker development plays an increasingly important role in oncology drug development pipelines and programs. Consequently, computer-based learning approaches have entered into use at multiple stages in pre-clinical and clinical pipelines. However, few approaches are available to identify interpretable and implementable biomarkers of response early in the drug development process when only small pre-clinical data packages are available. To address the need for early-stage biomarker development using pre-clinical tumor models, we have adapted the previously published Probabilistic Target Inhibitor Map (PTIM) platform to the challenge of biomarker hypothesis development, and denoted this approach the Probabilistic Target Map-Biomarker (PTM-Biomarker). In this article, we detail the history and design philosophy of PTM-Biomarker, and present two case studies using the biomarker discovery tool to illustrate its utility in guiding cancer drug development. © 2021 Wiley Periodicals LLC.

Due to the speed, efficiency, relative risk, and lower costs compared to traditional drug discovery, the prioritization of candidate drugs for repurposing against cancers of interest has attracted the attention of experts in recent years. Herein, we present a powerful computational approach, termed prioritization of candidate drugs (PriorCD), for the prioritization of candidate cancer drugs based on a global network propagation algorithm and a drug–drug functional similarity network constructed by integrating pathway activity profiles and drug activity profiles. This provides a new approach to drug repurposing by first considering the drug functional similarities at the pathway level. The performance of PriorCD in drug repurposing was evaluated by using drug datasets of breast cancer and ovarian cancer. Cross‐validation tests on the drugs approved for the treatment of these cancers indicated that our approach can achieve area under receiver‐operating characteristic curve (AUROC) values greater than 0.82. Furthermore, literature searches validated our results, and comparison with other classical gene‐based repurposing methods indicated that our pathway‐level PriorCD is comparatively more effective at prioritizing candidate drugs with similar therapeutic effects. We hope that our study will be of benefit to the field of drug discovery. In order to expand the usage of PriorCD, a freely available R‐based package, PriorCD, has been developed to prioritize candidate anticancer drugs for drug repurposing.

Background: Cancer drug expenditure is enormous and rising rapidly. There is potential for the waste of parenteral cancer drugs, ordered from external compounding companies, if patients are delayed or have treatment discontinued. Unused drugs can be orphaned and potentially reused in the future, for the same or other patients, up to their expiry date. Aim: This study evaluated the amount and cost of waste that could occur from orphaned cancer drugs having to be discarded, determined the amount and cost of waste that can be prevented by reuse, and identified strategies to prevent waste and optimise recycling. Methods: A prospective study over 6 months was undertaken to document information on all drugs orphaned. Doses, expiry dates, purchase costs, reasons for orphaning, how drugs were reused and why drugs were discarded were recorded. Results: Of 3379 drugs purchased, 412 were orphaned (12.2%), with 357 of these recycled (86.7%). The potential cost of orphaned drugs that could have been wasted was A$334,111. Of this, A$303,951 (91%) was saved via recycling, equating to 9.8% of the total expenditure on cancer drug products over 6 months. Conclusion: This study has important consequences for the health sector, demonstrating that significant cost savings can be realised by recycling cancer drugs. This directly affects the budgets of Australian hospitals using external compounding companies, and reduces claims on the Pharmaceutical Benefits Scheme. The study highlights the amount of wastage that can occur, and identifies strategies to prevent and reduce waste.

Drug development for cancer chemotherapy has an interesting history. A mix of serendipity, animal, cell line, and standard pharmacological principles of dose, dose-response, dose-concentration, dose intensity and combination therapies have been used to develop optimal dosing schedules. However in practice, significant gaps in the translation of preclinical to clinical dosing schedules persist, and clinical development has instead moved to new drug development. A older chemotherapies are still the backbone of most solid tumour schedules, therapeutic drug monitoring has emerged as a method for optimising the dose for individual patients.

A universal health care system has been a source of both identity and pride for Canadians for the last 6 decades. Currently, Canada actively negotiates the prices of cancer drugs but is not immune to their overwhelming financial toxicities. Prices of cancer drugs are set to ensure maximal profit based on what the market will bear rather than by the value they offer or solely because of the cost of research and development, as often is claimed by the manufacturers. The pan-Canadian Oncology Drug Review (pCODR) is mandated to provide funding recommendations to Canada's provinces and territories. For the most part, the pCODR has been crucial in assessing the cost-effectiveness and feasibility of new drugs in the Canadian context but it could assist more in safeguarding payers against extreme drug costs. Herein, the author suggests a few strategies by which national efforts such as the pCODR and its partners can help Canada to become a leader in facilitating value-based sustainable cancer care.

Background The clinical benefit and pricing of breakthrough-designated cancer drugs are uncertain. This study compares the magnitude of the clinical benefit and monthly price of new and supplemental breakthrough-designated and non-breakthrough-designated cancer drug approvals. Methods A cross-sectional cohort comprised approvals of cancer drugs for solid tumors from July 2012 to December 2017. For each indication, the clinical benefit from the pivotal trials was scored via validated frameworks: the American Society of Clinical Oncology Value Framework (ASCO-VF), the American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC), the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS), and the National Comprehensive Cancer Network (NCCN) Evidence Blocks. A high clinical benefit was defined as scores ≥ 45 for the ASCO-VF, overall survival gains ≥ 2.5 months or progression-free survival gains ≥ 3 months for all cancer types for the ASCO-CRC criteria, a grade of A or B for trials of curative intent and a grade of 4 or 5 for trials of noncurative intent for the ESMO-MCBS, and scores of 4 and 5 and a combined score ≥ 16 for the NCCN Evidence Blocks. Monthly Medicare drug prices were calculated with Medicare prices and DrugAbacus. Results This study identified 106 trials supporting approval of 52 drugs for 96 indications. Forty percent of these indications received the breakthrough designation. Among the included trials, 33 (43%), 46 (73%), 35 (34%), and 67 (69%) met the thresholds established by the ASCO-VF, ASCO-CRC, ESMO-MCBS, and NCCN, respectively. In the metastatic setting, there were higher odds of clinically meaningful grades in trials supporting breakthrough drugs with the ASCO-VF (odds ratio [OR], 3.69; P = .022) and the NCCN Evidence Blocks (OR, 5.80; P = .003) but not with the ASCO-CRC (OR, 3.54; P = .11) or version 1.1 (v1.1) of the ESMO-MCBS (OR, 1.22; P = .70). The median costs of breakthrough therapy drugs were significantly higher than those of nonbreakthrough therapies (P = .001). Conclusions In advanced solid cancers, drugs that received the breakthrough therapy designation were more likely than nonbreakthrough therapy drugs to be scored as providing a high clinical benefit with the ASCO-VF and the NCCN Evidence Blocks but not with the ESMO-MCBS v1.1 or the ASCO-CRC scale.

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short‐ and long‐term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long‐term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio‐oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long‐term follow‐up strategies for patients at risk of cancer therapy‐related cardiotoxicities. Research to better define strategies for early identification, follow‐up and management is highly necessary. Although the academic cardio‐oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross‐discipline interactions and help in the design and funding of cardio‐oncology trials. The overarching goals of cardio‐oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology.

Policy decisions about the approval and funding of new cancer drugs must often be made in an environment of complex uncertainty about clinical and cost-effectiveness data. The focus of this article is on the results from qualitative interviews with senior officials (n = 16) who make decisions about or influence cancer drug policy in various organizations in the Canadian cancer control system. Most participants identified the use of a limited number of informal approaches to address uncertainty, such as grounding decisions in evidence and advice from expert groups. People tended to focus on evidence informed decisions including price negotiations, the ability to implement policy changes, and stakeholder values. Lessons from the Canadian context related to continuing efforts to build a public culture of understanding into how policy decisions like cancer drug funding are made may result in greater acceptance and increased confidence in health policy decision-making processes across multiple sectors internationally.

Objective To examine the impact of the 340B drug discount program on the site of cancer drug administration and cancer care spending in Medicare. Data sources/study setting 2010-2013 Medicare claims data for a random sample of Medicare Fee-for-Service beneficiaries with cancer. Study design We identified the 340B effect using variation in the availability of 340B hospitals across markets. We considered beneficiaries from markets that newly gained a 340B hospital during the study period (new 340B markets) as the treatment group. Beneficiaries in markets with no 340B hospital were the control group. We used a difference-in-differences approach with market fixed effects. Data collection Secondary data analysis. Principal findings The probability of a patient receiving cancer drug administration in hospital outpatient departments (HOPDs) versus physician offices increased 7.8 percentage points more in new 340B markets than in markets with no 340B hospital. Per-patient spending on other cancer care increased $1,162 more in new 340B markets than in markets with no 340B hospital. Conclusions The 340B program shifted the site of cancer drug administration to HOPDs and increased spending on other cancer care. As the program expands, continuing assessment of its impact on service utilization and spending would be needed.

The successful development of new drugs with a companion diagnostic based on genomic alteration of an oncogene has led to rethinking of all phases on clinical development of cancer drugs. We critically review some of the new clinical trial designs for biomarker-based cancer drug development. We try to clarify the objectives of the new designs and examine completed trials using these designs to evaluate what has been learned about these designs.

BACKGROUND The objective of this study was to determine the impact of modeling cancer drug wastage in economic evaluations because wastage can result from single-dose vials on account of body surface area– or weight-based dosing. METHODS Intravenous chemotherapy drugs were identified from the pan-Canadian Oncology Drug Review (pCODR) program as of January 2015. Economic evaluations performed by drug manufacturers and pCODR were reviewed. Cost-effectiveness analyses and budget impact analyses were conducted for no-wastage and maximum-wastage scenarios (ie, the entire unused portion of the vial was discarded at each infusion). Sensitivity analyses were performed for a range of body surface areas and weights. RESULTS Twelve drugs used for 17 indications were analyzed. Wastage was reported (ie, assumptions were explicit) in 71% of the models and was incorporated into 53% by manufacturers; this resulted in a mean incremental cost-effectiveness ratio increase of 6.1% (range, 1.3%-14.6%). pCODR reported and incorporated wastage for 59% of the models, and this resulted in a mean incremental cost-effectiveness ratio increase of 15.0% (range, 2.6%-48.2%). In the maximum-wastage scenario, there was a mean increase in the incremental cost-effectiveness ratio of 24.0% (range, 0.0%-97.2%), a mean increase in the 3-year total incremental budget costs of 26.0% (range, 0.0%-83.1%), and an increase in the 3-year total incremental drug budget cost of approximately CaD $102 million nationally. Changing the mean body surface area or body weight caused 45% of the drugs to have a change in the vial size and/or quantity, and this resulted in increased drug costs. CONCLUSIONS Cancer drug wastage can increase drug costs but is not uniformly modeled in economic evaluations. Cancer 2017. © 2017 American Cancer Society.

Summary Investigator-initiated trials (IITs) are important aspects of medical research and have contributed substantially to modern oncology. IITs using post-approval drugs have been conducted by domestic institutions in Japan. Data from this study were obtained by all IITs registered clinical trials for five cancers (lung, colorectal cancer, gastric cancer, liver cancer, and breast cancer) using drugs approved from 1999 to 2009 in Japan. The Kaplan-Meier method, analysis of variance (ANOVA), and Kruskal-Wallis test were used to estimate time to enrolment completion (TTEC) and time to enrolment per patient (TTEP). Of 1,222 trials eligible for analysis, 465 trials (38%) completed enrolment to the studies, and 203 trials (17%) published results. In the distribution according to trial phase, 98 (8%) were phase I, 1,058 (87%) were phase I/II + II, and 66 (5%) were phase II/III + III. The accrual achievement and publication rates were higher in late-phase than in early-phase trials. The median TTEC was 1,387 days (95% confidence interval [CI], 1,302 to 1,472). The median TTEP was 38.5 days (95% CI, 34.5 to 42.5). The median TTEC and TTEP were significantly different in each trial phase (P < 0.01), funding source (P < 0.01), and publication status (median TTEC published trials vs. unpublished trial; 720 days vs. 1,672 days, median TTEP; 16 days vs. 55.8 days; P < 0.001). Many IITs using approved cancer drugs have been conducted; however, the quality of the clinical trials was low in terms of accrual achievement, publication rate, and time to publication of trial results. This article is protected by copyright. All rights reserved.

Lack of access to high-cost medications is a complex issue at the intersection of economics, medicine, politics, and ethics, and it poses a significant threat to global health care. The problem is even more significant in low- and middle-income countries, such as those in Latin America, where governments and individuals struggle to pay for products that are priced at several times the level of their per capita gross domestic product. In this review, we examine the determinants for increasing drug costs and how Latin American countries face this burgeoning crisis. We emphasize that a number of opportunities and strategies to reduce costs and improve access exist and should be identified and implemented, ideally within a regional approach with multiple stakeholders involved and based on systematic and transparent cost-effectiveness analyses. Cancer 2017;123:1313-1323. © 2016 American Cancer Society.

Measuring the potencies of small-molecule drugs in cell lines is a critical aspect of preclinical pharmacology. Such experiments are also prototypical of high-throughput experiments in multi-well plates. The procedure is simple in principle, but many unrecognized factors can affect the results, potentially making data unreliable. The procedures for measuring drug response described here were developed by the NIH LINCS program to improve reproducibility. Key features include maximizing uniform cell growth during the assay period, accounting for the effects of cell density on response, and correcting sensitivity measures for differences in proliferation rates. Two related protocols are described: one involves an endpoint measure well-suited to large-scale studies and the second is a time-dependent measurement that reveals changes in response over time. The methods can be adapted to other types of plate-based experiments. © 2017 by John Wiley & Sons, Inc.

While systemic immuno-oncology therapies have shown remarkable success, only a limited subset of patients benefit from them. Our Click Activated Protodrugs Against Cancer (CAPAC™) Platform is a click chemistry-based approach that activates cancer drugs at a specific tumor with minimal systemic toxicity. CAPAC Platform is agnostic to tumor characteristics that can vary across patients and hence applicable to several types of tumors. We describe the benefits of SQ3370 (lead candidate of CAPAC) to achieve systemic anti-tumor responses in mice bearing two tumors. SQ3370 consists of a biopolymer, injected in a single lesion, followed by systemic doses of an attenuated protodrug™ of doxorubicin (Dox). SQ3370 was well-tolerated at 5.9-times the maximum dose of conventional Dox, increased survival by 63% and induced a systemic anti-tumor response against injected and non-injected lesions. The sustained anti-tumor response also correlated with immune activation measured at both lesions. SQ3370 could potentially benefit patients with micro-metastatic lesions.

The headline figures from the oncology drugs pipeline look like a sabres-drawn cavalry charge that will sweep all before them. The statistics are impressive – 6484 products in active development across a range of novel mechanisms that can thwart cancer’s most malevolent mutations and variations. More than 2000 of these are first-in-class – according to the GBI Research’s Frontier Pharma: Versatile Innovation in Oncology report1 – as scientists get the upper hand in cracking genetic coding to deliver innovative disease-modifying therapies. Almost a decade of development following the first cancer genome sequencing report in 2006 has elevated the treatment of cancers to unprecedented levels of success. Clinicians now have a formidable arsenal to combat cancer from small molecule inhibitors to cure-delivering immunotherapies. The library of effective drug combinations is growing and, combined with a more muscular use of data, therapies can be targeted and stratified to promise enhanced survival and quality of life for cancer patients. Ambition is in the air. Cancer Research UK has recently invested in a Cambridge laboratory looking for antibodies against specific drug targets and it has launched a Grand Challenge to find ways of “drugging the undruggable” such as the Myc gene, which is an accelerant in a significant number of cancers. The potential suggests a fast approaching “And they all lived happily ever after” moment but, despite the genuine medical triumphs, discovery and delivery seem to run on different tracks and misconnecting timetables. As the consultation period for a recalibrated Cancer Drugs Fund (CDF) closes on 11 February, it is timely to ask if the trumpet-blaring is a little too soon and if the pipeline force will be reduced to a trickle by the time the patient is involved?

Marijuana (cannabis sativa), a schedule 1 drug has been recently approved by some of states in the US for its therapeutic benefit. Although few reports discuss about its anti-cancer potential, curr...

BACKGROUND: Adherence to endocrine therapy for breast cancer is often inadequate, in part due to medication out-of-pocket costs. Numerous states have enacted parity laws to limit patient cost-sharing for oral anticancer drugs. We sought to estimate the impact of these laws on patient copayments for and adherence to oral endocrine therapy for breast cancer. METHODS: Utilizing administrative health insurance claims data from 2007–2014 in the Clinformatics™ Data Mart Database (OptumInsight), we identified female patients aged 18–64 years with invasive cancer or ductal carcinoma in situ of the breast who initiated endocrine therapy and were enrolled in fully insured health plans in states that either enacted parity legislation between 2008 and 2013 or had not yet enacted legislation by 2015. Differences-in-differences analysis was used to compare copayments for and adherence to endocrine therapy during the one-year period before and after each year of legislation enactment. RESULTS: We identified 6,900 individuals with 7,778 unique drug therapy courses. Parity legislation was associated with significant decreases in the 25th percentile copayments for anastrozole of $4.39 (95% CI: −4.52 to −4.26; p

The p53-MDM2 complex is both a major target for cancer drug development and a valuable model system for computational predictions of protein-ligand binding. To investigate the accuracy of molecular simulations of MDM2 and its complex with p53, we performed a number of long (200 ns to 1 µs) explicit-solvent simulations using a range of force fields. We systematically compared nine popular force fields (AMBER ff03, ff12sb, ff14sb, ff99sb, ff99sb-ildn, ff99sb-ildn-nmr, ff99sb-ildn-phi, CHARMM22*, and CHARMM36) against experimental chemical shift data, and found similarly accurate results, with microsecond simulations achieving better agreement compared to 200-ns trajectories. Although the experimentally determined apo structure has a closed binding cleft, simulations in all force fields suggest the apo state of MDM2 is highly flexible, and able to sample holo-like conformations, consistent with a conformational selection model. Initial structuring of the MDM2 lid region, known to competitively bind the binding cleft, is also observed in long simulations. Taken together, these results show molecular simulations can accurately sample conformations relevant for ligand binding. We expect this study to inform future computational work on folding and binding of MDM2 ligands. Proteins 2015; 83:1665–1676. © 2015 Wiley Periodicals, Inc.

Although fungi produce highly structurally diverse metabolites, many of which have served as excellent sources of pharmaceuticals, no fungi-derived agent has been approved as a cancer drug so far. This is despite a tremendous amount of research being aimed at the identification of fungal metabolites with promising anticancer activities. This review discusses the results of clinical testing of fungal metabolites and their synthetic derivatives, with the goal to evaluate how far we are from an approved cancer drug of fungal origin. Also, because in vivo studies in animal models are predictive of the efficacy and toxicity of a given compound in a clinical situation, literature describing animal cancer testing of compounds of fungal origin is reviewed as well. Agents showing the potential to advance to clinical trials are also identified. Finally, the technological challenges involved in the exploitation of fungal biodiversity and procurement of sufficient quantities of clinical candidates are discussed, and potential solutions that could be pursued by researchers are highlighted.

In Australia, patients who want to access medicines that are not yet approved have only two options: to enroll in a clinical trial if they are eligible, or obtain their medicine through 'compassionate supply', which is provided at the discretion of the manufacturer. In this article, we explore ethical issues associated with the provision of oncology medicines that are still in development, either prior to regulatory approval or government reimbursement.

We compared and determined the reasons for any differences in the review and approval times of tyrosine kinase inhibitors (TKIs) by the US Food and Drug Administration (FDA) and the European EMA/CHMP. Applications for these novel cancer drugs were submitted to them within a mean of 31.2 days of each other, providing a fair basis for comparison. The FDA had granted priority review to 12 TKIs but the EMA/CHMP did not grant the equivalent accelerated assessment to any. The FDA granted accelerated approvals to six (38%) and CHMP granted (the equivalent) conditional approvals to four (29%) of these agents. On average, the review and approval times were 205.3 days in the US compared with 409.6 days in the European Union (EU). The active review times, however, were comparable (225.4 days in the EU and 205.3 days in the US). Since oncology drug development lasts about 7 years, the 20 days difference in review times between the two agencies is inconsequential. Clock stops during review and the time required to issue an approval had added the extra 184.2 days to review time in the EU. We suggest possible solutions to expedite the EU review and approval processes. However, post-marketing emergence of adverse efficacy and safety data on gefitinib and lapatinib, respectively, indicate potential risks of expedited approvals. We challenge the widely prevalent myth that early approval translates into early access or beneficial impact on public health. Both the agencies collaborate closely but conduct independent assessments and make decisions based on distinct legislation, procedures, precedents and societal expectations.

Innovation has frequently been described as the key to drug discovery. However, in the daily routine, medicinal chemists often tend to stick to the functional groups and structural elements they know and love. Blockbuster cancer drug Velcade (bortezomib), for example, was rejected by more than 50 companies, supposedly because of its unusual boronic acid function (as often repeated: "only a moron would put boron in a drug!"). Similarly, in the discovery process of the pan-CDK inhibitor BAY 1000394, the unconventional proposal to introduce a sulfoximine group into the lead series also led to sneers and raised eyebrows, since sulfoximines have seldom been used in medicinal chemistry. However, it was the introduction of the sulfoximine group that finally allowed the fundamental issues of the project to be overcome, culminating in the identification of the clinical sulfoximine pan-CDK inhibitor BAY 1000394. This Minireview provides an overview of a widely neglected opportunity in medicinal chemistry--the sulfoximine group.

The Cancer Drugs Fund was initiated in April 2011 as part of a Government scheme to enable patients to access the cancer drugs their doctors think will benefit them.1 In this Expert Panel Discussion, two oncology specialists and a Cancer Network Director discuss how well the fund is working. Copyright © 2012 Wiley Interface Ltd

Most cancer drugs are quite potent and represent a potential hazard to chemists conducting their synthesis. Chemical development teams must therefore integrate proper handing techniques for such compounds into their development plans. We describe the synthesis of the drug busulfan using barrier isolation technology. These systems are a general solution for the safe handling of many potent drugs, including those used to treat cancer. Drug Dev Res 71: 439–444, 2010. © 2010 Wiley-Liss, Inc.

Over the past 2 decades, our increased understanding of tumor biology has resulted in the delivery of a new generation of molecularly targeted cancer drugs with greater efficacy and less toxicity. This understanding has also provided pharmaceutical and academic institutions with a greater appreciation for the complexities and challenges associated with discovering and developing molecularly targeted drugs. To deal with the complexities of tumor biology and the associated technologies needed to develop molecularly targeted drugs, there has been increased cooperation and collaboration between academic and pharmaceutical-industry researchers in a broader number of aspects of the drug discovery and development continuum, including structural biology and translational research. This collaborative effort has played a role in molecularly targeted drugs such as cetuximab, trastuzumab, imatinib, and new promising drug candidates such as OSI-906. Cooperative efforts by industry and academia have also provided important insights to optimize the use of such agents in the clinic. This review aims to emphasize the need for academic/industrial collaborations for success and efficiency through the drug discovery and development continuum, and will highlight several examples of collaborations between academic and industrial scientists that facilitated the development of molecularly targeted antitumor agents into the clinic. Mt Sinai J Med 77:358–365, 2010. © 2010 Mount Sinai School of Medicine