Targeted Oncology (TARGET ONCOL)

Publications in this journal

• Article: Erratum to: Nuclear imaging of molecular processes in cancer

  Rafael Torres Martin de Rosales, Erik Årstad, Philip J. Blower
  Targeted Oncology 05/2012; 4(3):199-199.
• Article: Phase II combination of gefitinib and docetaxel for advanced or metastatic non-small cell lung cancer: clinical results and biological monitoring

  M. Gatineau, E. Dansin, F. Chomy, E. Lemarie, P. Nouyrigat, S. Oudard, R. Mouawad, A. Tisseron Carrasco, D. Khayat, O. Rixe
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  ABSTRACT: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib and the cytotoxic agent docetaxel are both used for the second-line treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of gefitinib in combination with docetaxel within this disease setting, and to evaluate the predictive value of assessing pre-treatment levels of soluble serum EGFR and HER2. In this open-label, non-comparative, multicenter, phase II trial, patients with non-resectable advanced or metastatic NSCLC were treated with oral gefitinib (250mg/day) in combination with docetaxel (75mg/m2 IV every 3weeks). Forty-eight patients were enrolled: 30 had progressed during or after platinum-based chemotherapy (Group A) and 18 were unsuitable for platinum-based chemotherapy (Group B). Anti-tumor activity was seen with objective response rates of 23.3% (Group A) and 11.8% (Group B). The most frequent adverse events considered to be gefitinib-related were diarrhea (57.4%) and skin-related events (dry-skin: 31.9%; rash: 29.8%; pruritus: 12.8%), and those considered to be docetaxel-related were alopecia (21.3%), nausea (19.1%), and diarrhea (17.0%). The addition of gefitinib did not seem to affect the hematological toxicity seen with docetaxel. Serum biomarker investigations revealed that patients who responded had lower serum EGFR levels than non-responders, although this association was not significant (p=0.07). In conclusion, the combination of gefitinib with docetaxel was feasible, generally well tolerated, and has activity for the treatment of advanced NSCLC. Soluble serum EGFR (and HER2 levels) did not appear to be predictive for response. Although this study confirms that the combination of gefinitib and docetaxel appears promisingly effective and tolerable, it should not be recommended as a standard option for second-line therapy in non-small cell lung cancer until results from phase III trials showing a significant superiority over docetaxel alone are available.
  Targeted Oncology 04/2012; 1(3):114-122.
• Article: Plasma cell leukemia: advantages of treatment with bortezomib

  N. Fraimout, B. Kadouch, M. Ticchioni, N. Mounier
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  ABSTRACT: Plasma cell leukemia is an aggressive variant of multiple myeloma affecting 4% of all cases of the latter. It is characterized by the presence of at least 20% plasma cells circulating in the peripheral blood, equivalent to an absolute number greater than 2,000/mm3. Plasma cell leukemia exits in two forms: primary or de novo plasma cell leukemia (60%) and the secondary form, which consists of a leukemia transformation of a multiple myeloma (40% plasma cell leukemia and 1% multiple myeloma). The disease is rare and has poor prognosis, as there is no effective therapy except the standard melphalan–prednisone combination. We report here on a case of primary plasma cell leukemia diagnosed in the Nice University Hospital’s Onco-hematology Department, which achieved complete response (CR) after eight cycles of bortezomib-cexamethasone followed by maintenance treatment with bortezomib.
  Targeted Oncology 04/2012; 3(4):265-267.
• Article: Angiogenesis and antiangiogenic treatment in lung cancer

  J. F. Morère, J. M. Brechot, R. Etessami
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  ABSTRACT: Angiogenic factors released by cancer cells increase structurally and functionally abnormal tumor micro-vascularization, resulting in metastases and progressive disease. Such diffusible factors bind to specific receptors of endothelial cells and activate the angiogenic signal pathway. Treatments with antiangiogenic monoclonal antibodies (e.g., bevacizumab) or using small molecules with anti-tyrosine kinase activity (e.g., sunitinib, sorafenib, ZD6474, erlotinib, or thalidomide) can block angiogenic signaling, lower blood tumoral irrigation, and improve chemotherapy distribution. Numerous studies have shown that a combination of biotherapy and chemotherapy can improve medical management of patients with advanced or metastatic non-small cell lung carcinomas. Biotherapy combination approaches also yield encouraging results promoting the development of targeted antitumor drugs.
  Targeted Oncology 04/2012; 1(4):215-219.
• Article: Targeted therapies in the treatment of advanced non-small cell lung cancer elderly patients

  C. Gridelli, P. Maione, A. Rossi, C. Ferrara, G. Colantuoni, F. Del Gaizo, D. Nicolella, C. Guerriero
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  ABSTRACT: More than 50% of lung cancer cases are diagnosed in patients over the age of 65 years, and about 30% are diagnosed in patients over the age of 70 years. Elderly patients do not tolerate chemotherapy as well as their younger counterparts, mainly because of the higher prevalence of comorbid conditions and organ failure in the elderly. Alternatives to conventional chemotherapy, such as new molecular targeted therapies, are of interest. This review summarizes current approaches and recent advances in the treatment of elderly patients with non-small cell lung cancer and gives a perspective on the future of molecular targeted therapies in this population. Epidermal growth factor receptor inhibitors and vascular endothelial growth factor inhibitors are discussed here, being, in our opinion, among the best candidates for clinical development in this setting. Their potential advantages in elderly patients include better tolerability than conventional chemotherapy.
  Targeted Oncology 04/2012; 1(1):13-22.
• Article: Second-line therapy with gefitinib in combination with docetaxel for advanced non-small cell lung cancer: a phase II randomized study

  G. Robinet, F. Barlesi, P. Fournel, H. Berard, R. Corre, A. Vergnenegre, L. Falchero, P-J. Souquet, A. Tisseron-Carrasco, C. Chouaid
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  ABSTRACT: This randomized, open-label, parallel-group, phase II study evaluated the efficacy and safety of gefitinib and docetaxel in combination, as second-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC). Eighty-nine patients who had failed first-line, platinum-based chemotherapy were randomly assigned to gefitinib (250mg/day orally) in combination with docetaxel (75mg/m2 every 3weeks) or single-agent docetaxel (75mg/m2 every 3weeks). Objective response rates were 6.8% with gefitinib plus docetaxel and 9.1% with docetaxel alone. Disease control was experienced by a higher proportion of patients receiving gefitinib plus docetaxel (59.1%) versus docetaxel alone (34.1%). Median progression-free and overall survival appeared to be longer with gefitinib plus docetaxel (3.9months [95% CI:2.3–5.4] and 7.6months [95% CI:5.4–10.4], respectively) than with docetaxel alone (2.1months [95% CI:2.1–3.7] and 6.2months [95% CI:5.2–7.2], respectively). The most common non-hematological adverse events were diarrhea, alopecia, rash and dry skin in the combination arm, and vomiting and asthenia with docetaxel alone. Gefitinib and docetaxel combination therapy has antitumor activity and may be a feasible treatment option in patients with advanced NSCLC who have failed platinum-based chemotherapy.
  Targeted Oncology 04/2012; 2(2):63-71.
• Article: Somatic von Hippel-Lindau (VHL) gene analysis and clinical outcome under antiangiogenic treatment in metastatic renal cell carcinoma: preliminary results

  Sophie Gad, Valentine Sultan-Amar, Jean-Baptiste Meric, Hassan Izzedine, David Khayat, Stéphane Richard, Olivier Rixe
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  ABSTRACT: Researchers have recently demonstrated a significant activity in the use of antiangiogenic compounds for the treatment of clear-cell metastatic renal cell carcinoma (RCC). The pVHL protein plays an important role in angiogenesis. Germline or somatic alterations of the VHL gene result in an abnormal accumulation of hypoxia inducible factor (HIF) inducing the upregulation of proangiogenic downstream genes. From a cohort of 13 patients with RCC included in a phase II study testing the activity of AG-013736 (axitinib), a multi-target receptor tyrosine kinase inhibitor (including VEGFR-1 and -2, PDGFR-β), we investigated the correlation between the presence of VHL somatic mutations and the activity of axitinib. Tumor samples collected were formalin-fixed paraffin-embedded tissues. DNA extracted from these samples were PCR-amplified and directly sequenced for the VHL gene. Among the 13 tumor DNA samples studied, 12 were successfully sequenced. There was an objective response in six patients. Two patients who experienced an objective response had evidence of VHL sequence variants. No VHL mutation was detected among the other patients. In conclusion, no correlation was observed between the somatic mutational status of the VHL gene and the objective response to axitinib in our series.
  Targeted Oncology 04/2012; 2(1):3-6.
• Article: Convection-enhanced delivery of liposomal doxorubicin in intracranial brain tumor xenografts

  Yoji Yamashita, Ryuta Saito, Michal T. Krauze, Tomohiro Kawaguchi, Charles Noble, Daryl C. Drummond, Dmitri B. Kirpotin, John W. Park, Mitchel S. Berger, Krystof S. Bankiewicz
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  ABSTRACT: We previously reported that convection-enhanced delivery (CED) of liposomes into brain tissue and intracranial brain tumor xenografts produced robust tissue distribution that can be detected by magnetic resonance imaging. Considering image-guided CED of therapeutic liposomes as a promising strategy for the treatment of brain tumors, we evaluated the efficacy of pegylated liposomal doxorubicin delivered by CED in an animal model. Distribution, toxicity, and efficacy of pegylated liposomal doxorubicin after CED were evaluated in a U251MG human glioblastoma intracranial xenograft model. CED of pegylated liposomal doxorubicin achieved good distribution in brain tumor tissue and surrounding normal brain tissue. Distribution was not affected by the particle concentration of pegylated liposomal doxorubicin, but tissue toxicity increased at higher concentrations. CED of pegylated liposomal doxorubicin, at a dose not toxic to normal rat brain (0.1mg/ml doxorubicin), was significantly more efficacious than systemic administration of pegylated liposomal doxorubicin at the maximum tolerated dose. CED of pegylated liposomal doxorubicin resulted in improved survival compared to CED of free doxorubicin at the same dose. Outcomes of this study suggest that CED of liposomal drugs is a promising approach for the treatment of glioblastoma.
  Targeted Oncology 04/2012; 1(2):79-85.
• Article: Targeted therapies for patients with advanced colorectal cancer: focus on cetuximab

  E. Van Cutsem, R. Labianca, F. Cognetti, J. Tabernero
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  ABSTRACT: Colorectal cancer (CRC) is the fourth most common cancer in men and the third in women worldwide. Combinations of 5-fluorouracil (5-FU)/folinic acid (FA) with irinotecan or oxaliplatin form the standard treatment approaches for metastatic disease. The introduction of targeted agents has presented the opportunity to improve on the efficacy of current treatments without exacerbating the associated toxicity. Cetuximab (Erbitux®) is an IgG1 monoclonal antibody (MAb) that specifically targets the epidermal growth factor receptor (EGFR) with high affinity and competitively inhibits endogenous ligand binding. Cetuximab has shown good efficacy in combination with irinotecan in CRC that had previously progressed on irinotecan-based therapy. Cetuximab plus irinotecan and various schedules of 5-FU/FA have shown efficacy in a first-line setting. The activity of cetuximab and oxaliplatin-based regimens is being investigated in both first- and subsequent-line settings. Cetuximab is well tolerated and does not increase the side effect profile of agents it is combined with. Other EGFR inhibitors, including the tyrosine kinase inhibitors, gefitinib and erlotinib, and the MAbs, panitumumab and matuzumab, are also being investigated in a number of solid tumors. The vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, although apparently inactive as a single agent, has demonstrated survival benefits when combined with bolus 5-FU/FA and irinotecan in a first-line setting and with 5-FU/FA and oxaliplatin in the second-line treatment of metastatic CRC. In this paper we discuss the use of targeted therapies in the treatment of metastatic CRC, with a focus on cetuximab.
  Targeted Oncology 04/2012; 1(1):2-12.
• Article: Improving drug penetration in tumors by targeting tumor vascularization

  Ferdy J. Lejeune
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  ABSTRACT: Clinical oncologists have not been paying enough attention to the fact that poor tumor penetration represents a major impediment to the efficiency of cancer chemotherapeutics. The cytokine tumor necrosis factor (TNF) was the first treatment shown to affect tumor vessel destruction and improve vascular permeability of drugs in a clinical setting. TNF produces an early increase of vessel permeability followed by a dual targeting: TNF induces apoptosis of intratumoral angiogenic endothelial cells and melphalan during the apoptosis of tumor cells. Given the systemic toxicity, TNF has to be administered by regional therapy. However, experimental data indicate that a systemic approach will be possible, thanks to TNF targeting. Three fusion proteins with TNF were shown to target tumors: anti-EDB fibronectin/TNF, Asn-Gly-Arg-TNF, and anti-gp240/TNF. Current approaches to blocking angiogenesis include strategies that target vascular endothelium growth factor (VEGF)-A. However, little attention has been paid to possible drawbacks, which may include vessel destruction and reduced penetration by chemotherapeutic agents administered simultaneously or subsequently. An antiangiogenic treatment is optimal when it is given at a critical dose and at a critical time. Current protocols seem not to take these prerequisites into consideration. Other new approaches to increased tumor vessel permeability include histamine and combretastatin analog. The current paradigm of antitumor strategy based on the synergism of empirical drug combinations is obsolete. Instead, the design of protocols based on new pharmacodynamic concepts should provide better efficiency of cancer treatment as exemplified in the use of TNF and anti-VEGF antibody.
  Targeted Oncology 04/2012; 1(2):90-96.
• Article: The clinical challenge of imatinib resistance in chronic myeloid leukemia: emerging strategies with new targeted agents

  Elias Jabbour, Jorge Cortes, Francis Giles, Susan O’Brien, Hagop Kantarjian
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  ABSTRACT: Chronic myelogenous leukemia (CML) is a progressive and often fatal hematopoietic neoplasm. The disease is characterized by the presence of the Philadelphia chromosome, which arises following a balanced translocation between chromosomes 9 and 22, creating the BCR-ABL fusion gene. It is often stated that the only proven curative option is allogeneic stem cell transplantation (allo-SCT), which is indicated for only a limited subset of patients. The Bcr-Abl tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) represented a major advance over conventional CML therapy. Following IM treatment, more than 90% of patients obtain complete hematologic response, and 70–80% of patients achieve a complete cytogenetic response. Resistance to IM represents an increasing clinical challenge and is often a result of point mutations causing a conformation change in Bcr-Abl, which impair IM binding. Novel targeted agents designed to overcome IM resistance, including multitargeted TKIs and farnesyl transferase inhibitors, are in various phases of development. Dasatinib, which has recently become available in the clinic, is a Bcr-Abl TKI that also inhibits Src, c-Kit, platelet-derived growth factor receptor, and ephrin A receptor kinases. In a phase II randomized trial in patients resistant or intolerant to IM, patients receiving dasatinib had better hematologic and cytogenetic responses than those on high-dose IM, irrespective of the presence or absence of mutations. Nilotinib has also shown promising activity. Combining IM with conventional chemotherapy, interferon, and targeted agents including TKIs is being actively pursued. Diagnostic testing may enable individualized targeted treatment so that patients receive the most effective agent first-line.
  Targeted Oncology 04/2012; 1(4):186-196.
• Article: Histone deacetylase inhibitors as a potential therapeutic agent for human cancer treatment

  G. Kouraklis, E. P. Misiakos, S. Theocharis
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  ABSTRACT: Recent evidence pointed that remodeling of the chromatin template by inhibition of the enzyme histone deacetylase could be a promising approach for the treatment of human cancer. Alterations in histone acetylation may lead to changes in chromatin structure and transcriptional dysregulation of genes that are implicated in controlling cell cycle progression or pathways regulating cell differentiation and apoptosis. The histone deacetylase (HDAC) inhibitors are currently a new class of antineoplastic agents. They bind DNA tightly to histones, preventing the transcription of several tumor suppression genes without modifying DNA sequence. At present, there are already too many HDAC inhibitors available and hopefully some of them could help substantially in the prevention and treatment of cancer. First clinical studies have shown that histone hyperacetylation can be achieved safely in humans and that treatment of cancer with such agents seems to be becoming possible. Several ongoing National Institute of Health (NIH) trials are investigating the use of these agents in combination with potent chemotherapeutic agents, with the aim of increasing their efficiency. Further studies are needed to delineate the optimal dosage, the duration of therapy and possibly the efficacy of other agents able to synergize with HDAC inhibitors in the fight against cancer.
  Targeted Oncology 04/2012; 1(1):34-41.
• Article: What is the impact of biologicals in colorectal cancer?

  Rachel Wong, David Cunningham
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  ABSTRACT: An impressive array of therapeutic biological agents is currently being studied in the treatment of colorectal and other cancers. In advanced colorectal cancer, the majority of evidence currently available supporting the use of biological agents outside clinical trials involves the monoclonal antibodies cetuximab and panitumumab, which are epidermal growth factor receptor (EGFR) inhibitors, and the vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab. Ongoing studies are underway to see if benefits are transferable into the adjuvant setting. The role of small molecules that inhibit the EGFR and VEGF receptors in colorectal cancer is yet to be determined. This article reviews the current clinical evidence regarding the use of biological agents in colorectal cancer and the potential impact on day-to-day management of this common clinical condition.
  Targeted Oncology 04/2012; 3(2):59-69.
• Article: Combination of epidermal growth factor receptor inhibitors and antiangiogenic drugs: a model for treatment

  Erika Martinelli, Teresa Troiani, Floriana Morgillo, Maria Carmela Piccirillo, Katia Monaco, Maria Pia Morelli, Tina Cascone, Fortunato Ciardiello
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  ABSTRACT: The epidermal growth factor receptor (EGFR) autocrine pathway plays a crucial role in human cancer since it contributes to relevant processes in tumor development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis and metastatic spread. EGFR-blocking monoclonal antibodies and small-molecule EGFR tyrosine kinase inhibitors have been developed as anticancer drugs. Although anti-EGFR agents are active in a subset of cancer patients, constitutive resistance in a large number of patients and the development of acquired resistance in initially responding patients are a relevant clinical issue. A major problem is that intrinsic and/or acquired resistance can occur, and it could be due to the activation of alternative cancer cell growth controlling pathways. One mechanism linked to acquired resistance to EGFR-inhibitor treatment, in particular, is the activation of uncontrolled, tumor-induced angiogenesis through an increase in vascular endothelial growth factor (VEGF) secretion by cancer cells. Significant and sustained antitumor activity in this context can be obtained by combining selective anti-EGFR drugs with antiangiogenic agents. In this review, we focus on the preclinical and clinical evidence showing that an approach combining anti-EGFR and antiangiogenic drugs is feasible and could represent a paradigm for a rational combined multi-targeted treatment of cancer.
  Targeted Oncology 04/2012; 1(3):123-129.
• Article: Targeted therapy for chronic lymphocytic leukemia

  Alfonso Quintás-Cardama, Susan O’Brien
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  ABSTRACT: The introduction of targeted agents such as the monoclonal antibodies rituximab (anti-CD20) and alemtuzumab (anti-CD52) has brought about a remarkable change in the therapy of chronic lymphocytic leukemia (CLL). Although it is unclear whether overall survival has been improved, the incorporation of these monoclonal antibodies into chemoimmunotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both newly-diagnosed and relapsed CLL. The success of rituximab and alemtuzumab has spurred the development of other monoclonal antibodies targeting distinct proteins and epitopes on the surface of CLL cells and an exciting array of novel immunotherapeutics. The judicious use of these agents provides the opportunity to develop risk-adapted therapeutic strategies to optimize responses and quality of life in patients with CLL.
  Targeted Oncology 04/2012; 4(1):11-21.
• Article: Combining targeted therapies

  Xabier García-Albeniz, Alejandro Martinez-Fernandez, Pere Gascon
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  ABSTRACT: Therapeutics in oncology are rapidly changing, with the advent of the so-called “targeted drugs.” A clear example is trastuzumab, an anti-HER2 monoclonal antibody, and its role in the treatment of breast cancer. Trastuzumab was followed by other monoclonal antibodies like cetuximab (anti-EGFR) and bevacizumab (anti-VEFG) and by tyrosine kinase inhibitors such as imatinib, gefitinib (anti-EGFR) and others. The complex biology of the cancer cell leads us to search combination strategies to act simultaneously in different points of signals transduction pathways to enhance the anticancer effect. Here we review various clinical trials and also experimental data exploring these new drugs in combination. Combination with chemotherapy is beyond the scope of this review. For this review, we have selected the following agents: cetuximab, trastuzumab, bevacizumab, panitumumab, imatinib, erlotinib, gefitinib, sorafenib, sunitinib, and lapatinib.
  Targeted Oncology 04/2012; 2(4):241-252.
• Article: Mechanisms of resistance to EGFR inhibitors

  Roberto Bianco, Teresa Gelardi, Vincenzo Damiano, Fortunato Ciardiello, Giampaolo Tortora
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  ABSTRACT: The epidermal growth factor receptor (EGFR) autocrine pathway plays a crucial role in human cancer, contributing to a number of highly relevant processes in tumor development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis, and metastatic spread. For these reasons, the EGFR is one of the most studied and exploited targets for molecular cancer therapy. Two classes of anti-EGFR agents have entered clinical practice: monoclonal antibodies and small molecules targeting the receptor tyrosine kinase. They have shown activity alone and in combination with conventional antitumor treatments, such as chemotherapy or radiation therapy. However, preclinical and clinical studies have demonstrated the occurrence of spontaneous or acquired resistance to these drugs. Since EGFR is implicated in a wide array of intracellular functions, the phenomenon of resistance to its inhibitors may result from the derangement of different molecular pathways, including autocrine/paracrine production of ligands, receptor mutations, constitutive activation of downstream signaling proteins, and activation of alternative pathways. This review presents the experimental evidence underlying the main mechanisms of resistance to EGFR inhibitors.
  Targeted Oncology 04/2012; 2(1):31-37.
• Article: Molecular imaging in clinical trials

  Debra Josephs, James Spicer, Michael O’Doherty
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  ABSTRACT: Imaging of biological processes using specific molecular probes allows exploration of the mechanism of action and efficacy for new therapies. This molecular imaging has made use of modalities including single photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI), and optical techniques. Molecular imaging can be used to explore many of the hallmarks of cancer biology, including angiogenesis, proliferation, tissue invasion, evasion of apoptosis, and self-sufficiency in growth signals. Since many of these aspects of cancer biology are in turn the targets of novel therapies in development, molecular imaging techniques have great potential to inform trials of these new agents. The high cost of clinical drug development mandates the optimisation of early phase trial design to maximise the collection of evidence for efficacy and proof of mechanism, endpoints which have, in a number of examples, already been provided by molecular imaging. The variety provided by novel chemistry, and the availability of isotopes with varying physical properties, particularly suits PET imaging as a functional modality for application in clinical trials.
  Targeted Oncology 04/2012; 4(3):151-168.
• Article: Targeted therapies in head and neck cancer

  Pol M. Specenier, Jan B. Vermorken
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  ABSTRACT: Over the past decade, the important role of different growth factors and their receptors and signal transduction pathways in the genesis and progression of tumors has been well recognized and their mechanism of action and interactions is gradually being unraveled. Epidermal growth factor receptor (EGFR) overexpression is present in the vast majority of squamous cell head and neck cancers and carries a worse prognosis. EGFR is the target of multiple specifically targeted monoclonal antibodies and tyrosine kinases, which are in various stages of clinical development in squamous cell carcinoma of the head and neck (SCCHN). The search for EGFR mutations is an area of active investigation. The incidence and impact of EGFR mutations in SCCHN has yet to be determined. EGFR downstream signaling pathways are the target of farnesyltransferase inhibitors (FTIs) and mammalian target of rapamycin (mTOR) inhibitors. Cyclooxygenase-2 (COX-2) is overexpressed in premalignant lesions (oral leukoplakia) and in squamous cell carcinoma of the head and neck. EGFR and COX-2 signaling pathways form a positive feedback loop. As their toxicity profiles are non-overlapping, combination of COX-2 inhibitors and EGFR targeted therapies looks attractive. The majority of the studies, although not all, examining the prognostic significance of vascular endothelial growth factor (VEGF) expressing did observe a worse outcome in patients with SCCHN expressing VEGF and VEGF receptor 2 (VEGFR-2). Anti-VEGF strategies include neutralizing antibodies to VEGF or VEGFR and VEGFR tyrosine kinase inhibitors. Aurora kinase inhibitors, insulin like growth factor inhibitors, and histone acetylase inhibitors have recently gained interest as potential new promising ways of tackling tumors including SCCHN.
  Targeted Oncology 04/2012; 2(2):73-88.
• Article: The intersection of sunitinib with the immunosuppressive microenvironment of renal cell carcinoma: implications for future therapeutics

  Renee N. Salas, James H. Finke, Brian I. Rini
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  ABSTRACT: Renal cell carcinoma (RCC) is known to be a model of an immune-influenced malignancy. The immunobiology of RCC has three main immune cell types known to contribute to immunosuppression: T regulatory (Treg) cells, Type 2 T helper (Th2) cells, and myeloid derived suppressor cells. Sunitinib has rapidly revolutionized RCC treatment and is now a first-line standard of care for advanced RCC. Preliminary evidence reviewed here reveals that, in addition to antiangiogenic effects, sunitinib may have a direct or secondary effect on reversing the immunosuppressive environment by decreasing Treg cells and reversing the Th2 bias. Hypotheses for these observed effects and others are postulated based upon the mechanism of action. Current research is underway to further delineate the effect sunitinib has on the immune system and its mechanisms. Future therapeutics in RCC may include combination therapies that function collaboratively with sunitinib to harness an antitumor immune effect.
  Targeted Oncology 04/2012; 2(4):225-234.