A free glossary of oncology-related terms and resource organizations.
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Unlike reports that are 'dead on arrival' nm|OK is a constantly updated comprehensive report on every aspect of oncology drug development. click
Drugs profiled in nm|OK
nm|OK profiles over 4,310 drugs/in vivo imaging agents in development:
3,653 anticancer agents addressing over 100 cancer types and thousands of clinical indications. Of these, 1,695 are in active development; 821 have been or are currently being evaluated in clinical trials and 539 of these are targeted agents.
757 drugs for the management of complications of cancer and its treatment (pain, infection, mucositis, emesis, etc.)
nm|OK also profiles over 552 marketed drugs (anticancer agents=335, adjuncts=197) globally, providing trial results from monotherapy and combination therapy trials.
In vitro testing (IVT) products
nm|OK profiles over 200 companies and hundreds of products (screening tests, diagnostics, pharmacogenomics, prognostics, disease monitoring tests, theragnostics, etc.) in the in vitro testing area in oncology.
Enabling technologies/drug delivery
nm|OK describes hundreds of technology platforms used to discover, evaluate, optimize, and or deliver anticancer agents such as cytotoxics, synthetic nucleic acid sequences, small molecule drugs, monoclonal antibodies, fusion proteins, etc.
Targets in oncology
nm|OK describes over 1,000 molecular moieties that may be target candidates of anticancer strategies or used as in vitro testing markers.
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The headlines below refer to selected records among the hundreds updated in nm|OK within a 30-day period. A summary of the updated information, the complete records for each item on the list, and numerous other updated entries are available to subscribers upon logging in. Samples of records from each module are here.
Special reports are reviews of current developments of oncology and related drugs by indication, mechanism, delivery technology, etc. as well as personalized medicine, including biomarkers, diagnostics, theragnostics, prognostics, pharmacogenomics, disease monitoring tests, etc. Samples of special reports are here.
Idelalisib CAL-101, GS-1101
BP-100-1.01, Liposomal Grb-2, L-Grb2
EPZ005687, EPZ-6438, E7438
Tivozanib AV-951, formerly KRN951
BKT-140, BTK140, BL-8040
Pexastimogene devacirepvec JX-594, JX594, TG6006
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Targets in Oncology
Breast cancer 1 (BRCA1)
Breast Cancer 2 (BRCA2)
Enhancer of zeste homolog 2 (EZH2)
Lactate dehydrogenase B (LDHB)
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SCOTUS Rules That Human Genes Cannot be Patented
In June 2013, the Supreme Court overturned a lower Federal court decision that allowed Myriad Genetics' patent of two human genes, BRCA-1 and BRCA-2. Despite alarmist forecasts that the inability to patent naturally existing genes would stifle innovation in the biotechnology sector, this groundbreaking decision rendered unanimously by the Supreme Court is expected to open up this area to uninhibited development of novel and superior technologies and products. Myriad's patents on its tests to detect BRCA-1 and BRCA-2 are unaffected by this decision and remain valid through to their normal date of expiration These patents were originally granted by the USPTO in 1997. In May 2004, an opposition division at the European Patent Office (EPO) had decided to revoke the Myriad patents, which parenthetically were rarely enforced in Europe by Myriad. The Court, however allowed Myriad's patents on complementary DNA (cDNA), which refers to DNA synthesized from a messenger RNA (mRNA) template in a reaction catalyzed by the enzymes reverse transcriptase and DNA polymerase to produce gene clones.
HEr2 Inhibitors May Benefit Patients with Hormone Receptor-positive Breast Cancer Irrespective of the Level of HEr2 Expression
Although current breast cancer treatment guidelines limit the use of HEr2-blocking agents to tumors with HEr2 overexpression/gene amplification, retrospective analyses suggest that a wider group of patients may benefit from this therapy. In a serendipitous finding, investigators conducting a pivotal clinical trial (protocol ID: NSABP B-31; NCT00004067) to evaluate Herceptin in the adjuvant setting failed to detect either higher gene copies (by HEr2 FISH testing) or elevated mRNA levels in a number of responders. Surprisingly, patients with HEr2-negative breast cancer benefited as much from adjuvant trastuzumab therapy as women whose tumors displayed classical HEr2 amplification (Paik S, etal, NEM, 27 Mar 2008; 358:1409-1411). Similar results have been reported by others, providing confirmation of the results from this trial. Based on these findings, the restriction, based on the demonstrated clinical efficacy of HEr2 blockade in women with HEr2-amplified tumors in advanced stages of disease and adjuvant settings could be lifted if ongoing trials demonstrate the effectiveness of HEr2 inhibitors in patients with hormone-positive breast cancer irrespective of HEr2 expression status.
Confirmation of these results in clinical trials would dramatically expand the market for HEr2 inhibitors. In addition to trastuzumab (Herceptin), other currently marketed HEr2 inhibitors include lapatinib (Tykerb), pertuzumab (Perjeta), and T-DM1 (Kadcyla). Also, more than 58 novel HEr2 inhibitors have been investigated since the approval and launch of Herceptin in the USA in 1998; 35 have entered clinical trials; and 17 are currently in clinical development for various indications.
Worldwide sales of Herceptin alone, for the treatment of breast cancer grew from $645 million in 2002, when it was first launched globally, to $5,028 million in 2010, before it was approved for other indications. Expanded use of HEr2 inhibitors in HEr2-negative breast cancer could easily double the market, even if such inhibitors were used only in selected populations.
Herceptin May Prevent Bone Metastasis in Hormone Receptor-Positive Breast Cancer Irrespective of the Level of HEr2 Expression
Using breast cancer cell lines, mouse xenograft models and matched human primary and metastatic tissues, investigators at the University of Michigan (Ann Arbor, MI) reported that HEr2 is selectively expressed and regulates self renewal of the cancer stem cell (CSC) population in estrogen receptor-positive (Er+), HEr2+ luminal breast cancer. Although trastuzumab had no effect on the growth of established mouse xenografts of such cells, the drug blocked subsequent tumor growth. (more free...)
ODAC Declines to Recommed Tivozanib for the Treatment of Advanced Renal Cell Carcinoma (RCC)
In May 2013, FDA's ODAC in a 13 to 1 vote declined to recommend Aveo Pharmaceuticals' tivozanib for the treatment of patients with metastatic renal cell carcinoma (RCC). Aveo Pharmaceuticals had submitted an NDA for tivozanib in September 2012 that was supported by TIVO-1, a single phase III clinical trial, a randomized phase II trial (protocol ID: AV-951-12-205; NCT01673386), and an extension/crossover trial (protocol ID: AV-951-09-902, 2009-015987-32; NCT01076010); in total, Aveo submitted findings from 17 trials involving more than 1,000 patients. ODAC reviewed the findings of the TIVO-1 (TIvozanib Versus SOrafenib in 1st line Advanced RCC) open label phase III clinical trial (protocol ID: AV-951-09-301; NCT01030783) that enrolled 517 patients who were randomly allocated 1:1 to either tivozanib or sorafenib (Nexavar). The primary endpoint was PFS as determined by an independent review committee and the secondary endpoint was OS. According to the results from this trial, there was a statistically significant improvement in PFS with tivozanib (HR=0.80, p=0.04); median PFS was 11.9 months in the tivozanib arm versus 9.1 months in the sorafenib arm. However, there was a trend toward a detrimental effect on OS with tivozanib (HR=1.25, p=0.11); median OS was 28.8 months in the tivozanib arm versus 29.3 months in the sorafenib arm. ODAC concluded that the trial did not provide a favorable benefit-to-risk ratio for the treatment of advanced RCC.
A Three-drug Combination Produces 100% Response in Patients With Newly Diagnosed Advanced Mantle Cell Lymphoma (MCL)
In a small phase I/II clinical trial (protocol ID: MERCK-OHSU-4180; NCT00764517), treatment with the combination of vorinostat (Zolinza), the hypomethylating agent cladribine, and rituximab (Rituxan) resulted in a 100% response in a subgroup of 37 evaluable chemotherapy-naïve patients with advanced mantle cell lymphoma (MCL) including 35 complete responses (CR); a response was noted in 29/32 (91%) patients treated with at least 6 cycles of the combination therapy. The majority of patients were >/=60 years of age (median age=64), and 95% had Stage IV disease. Most of the responders have continued maintenance therapy with rituximab. PFS could not be estimated after a follow-up of 34 months. Reversible myelosuppression is the primary toxicity of this regimen consisting of neutropenia in 32% (Grade 3/4=11%) and thrombocytopenia in 20% (Grade 3/4=5%) of patients. Fatigue was the most common nonhematologic toxicity. Dramatic responses and CR were also seen albeit in fewer patients with low grade NHL, but not in those with diffuse large B cell lymphoma (DLBCL). Based on these results, further clinical evaluation is warranted with this regimen in MCL and in other B-cell hematologic malignancies (Hasanali Z, etal, AACR13, Abs. LB-140).
Back to the Future-The Return of Biologics in the Treatment of Cancer
Cancer drug developers are increasingly turning to the development of biologics after more than a decade of intensive emphasis on oral small molecule drugs, spurred more by the attractiveness of oral administration than by science. Positive clinical findings are driving the development of immunoconjugates/fusion proteins, autologous cancer vaccines, RNAi drugs, and various other biologic constructs. Over 350 distinct biologics have entered clinical development in cancer since 2000 and numerous autologous vaccine approaches have been investigated in academic institutions.
Cancer immunotherapy is a case in point. Immunotherapy as a cancer treatment strategy predates almost all other approaches. However, progress in this area was stalled when cytotoxics and molecularly targeted agents assumed center stage because the former were mostly based on approved similar agents and the latter are simpler to develop, manufacture and administer to patients. The lackluster performance of targeted inhibitors has revived intense interest in immunotherapy as a more generalized approach to combating malignancy. Immunotherapeutics circumvent the issues of resistance/escape mechanisms that have dogged targeted approaches and the adverse effects of compounded toxicities resulting from the necessity of combining targeted agents with cytotoxics to bolster effectiveness. Currently, a new wave of more effective immune system-based approaches, including autologous cancer vaccines, is rapidly changing the cancer therapeutics development landscape.
Stand Up To Cancer (SU2C) Forms Immunologic Checkpoint Blockade and Adoptive Cell Transfer Cancer Therapy Dream Team
In December 2012, Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) formed of a Dream Team project "Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy," dedicated to cancer immunology. (more free...)
MedImmune Joins Forces With the Cancer Research Institute (CRI), the Ludwig Institute for Cancer Research to Advance Novel Immunotherapy Research
In October 2012, the Cancer Research Institute (CRI), the Ludwig Institute for Cancer Research and MedImmune, the global biologics arm of AstraZeneca, signed a collaboration agreement to advance the research of immunotherapy in cancer by focusing on clinical trials to test novel combinations of immunotherapies. In addition, after reshuffling its senior management team, AstraZeneca announced in January 2013 its intention to equally rank R&D between immunotherapies and traditional small molecule drugs, reflecting the general trend favoring this sector. (more free...)
Novartis Forges Cancer Immunotherapy Alliance with the University of Pennsylvania
The recently forged exclusive global research and licensing agreement between Novartis and the University of Pennsylvania is aimed at bringing a new, personalized immunotherapy approach to patients with a wide variety of malignancies. Under this August 2012 agreement, novel cellular immunotherapies using chimeric antigen receptor (CAr) approaches will be evaluated and eventually commercialized. (more free...)
Inhibition of the Vascular Endothelial Growth Factor (VEGF) Pathway for the Treatment of Cancer
The success of Avastin, an antiangiogenesis agent targeting the VEGF pathway, has prompted the development of numerous similarly acting agents. Avastin, with global revenues of $6,210.5 million in fiscal 2010, is the most commercially successful anticancer drug ever to reach the market. Future Oncology has published a review of VEGF inhibition in the treatment of cancer. (more...)
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