The Experts below are selected from a list of 17628 Experts worldwide ranked by ideXlab platform

Brian I Rini - One of the best experts on this subject based on the ideXlab platform.

  • recent advances in Molecularly Targeted Therapy in advanced renal cell carcinoma
    Therapy, 2009
    Co-Authors: Jenny J Kim, Brian I Rini
    Abstract:

    In the last few years, enhanced understanding of the biology of clear cell renal cell carcinoma has led to the development of molecular signaling inhibitors, which, with their superior anti-tumor activity demonstrated in randomized clinical trials, have led to a paradigm shift in the treatment of advanced renal cell carcinoma from cytokine-based Therapy to signaling-inhibitor Therapy. Relevant therapeutic signaling pathways that have emerged are VEGF receptor and mammalian target of rapamycin pathways, and signaling inhibitors sunitinib, sorafenib, temsirolimus and, most recently, everolimus are approved by the FDA for treatment of advanced renal cell carcinoma in the USA. Newer agents with promising anti-tumor activity are in continued development, as are efforts to uncover additional therapeutic targets. Currently, the optimal use of available agents, such as sequence and combination strategies, as well as their role in the adjuvant and neoadjuvant setting, remain unclear and investigative efforts are underway.

  • clinical effect and future considerations for Molecularly Targeted Therapy in renal cell carcinoma
    Urologic Oncology-seminars and Original Investigations, 2008
    Co-Authors: Brian I Rini, Keith T Flaherty
    Abstract:

    Vascular endothelial growth factor (VEGF) pathway activation leads to the angiogenic phenotype of renal cell carcinoma (RCC). Several different strategies targeting various aspects of this pathway have emerged as standard Therapy in metastatic RCC. Bevacizumab, a VEGF ligand-binding antibody, sunitinib and sorafenib, small molecule inhibitors of the VEGF receptor, as well as temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR) have all shown substantial clinical activity in metastatic RCC. Several relevant clinical aspects have also emerged with use of these agents such as defining resistance, measurement of response, and combination Therapy.

  • seminar article clinical effect and future considerations for Molecularly Targeted Therapy in renal cell carcinoma
    2008
    Co-Authors: Brian I Rini, Keith T Flaherty
    Abstract:

    Vascular endothelial growth factor (VEGF) pathway activation leads to the angiogenic phenotype of renal cell carcinoma (RCC). Several different strategies targeting various aspects of this pathway have emerged as standard Therapy in metastatic RCC. Bevacizumab, a VEGF ligand-binding antibody, sunitinib and sorafenib, small molecule inhibitors of the VEGF receptor, as well as temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR) have all shown substantial clinical activity in metastatic RCC. Several relevant clinical aspects have also emerged with use of these agents such as defining resistance, measurement of response, and combination Therapy. © 2008

  • Molecularly Targeted Therapy in renal cell carcinoma where do we go from here
    Expert Review of Anticancer Therapy, 2006
    Co-Authors: Brian I Rini
    Abstract:

    The angiogenic phenotype of renal cell carcinoma results from vascular endothelial growth factor pathway activation. Several different strategies targeting various aspects of the pathway have emerged as clinically relevant therapeutics in metastatic renal cell carcinoma. Key clinical data regarding these approaches are presented in this article. Furthermore, there are several considerations as to the further development of these agents and their appropriate application in metastatic renal cell carcinoma, such as timing of Therapy, choice of initial Therapy, continued role of debulking nephrectomy and toxicity concerns. These issues are discussed in light of current data and strategies for further drug development are presented.

  • Molecularly Targeted Therapy in renal cell carcinoma
    Expert Review of Anticancer Therapy, 2005
    Co-Authors: Kimryn W Rathmell, Tricia M Wright, Brian I Rini
    Abstract:

    Recent developments in the molecular biology of renal cell carcinoma have identified multiple pathways associated with the development of this cancer. Multiple strategies have been investigated targeting these pathways, with significant clinical benefits shown in early studies. This review aims to overview the findings of recent clinical trials and clarify the development of these compounds for use in renal cell carcinoma. The authors also aim to clarify the molecular pathways implicated in renal cell carcinoma and the clinical results in metastatic renal cell carcinoma with agents targeting these pathways. The relevant literature was reviewed concerning pathways implicated in the pathophysiology of renal cell carcinoma including pathways activated secondary to von Hippel-Lindau gene inactivation and PI-3 kinase/Akt/mammalian target of rapamycin pathway activation. Therapeutic targeting based upon underlying molecular biology in renal cell carcinoma has strong rationale. Substantial clinical activity has ...

Brian J Druker - One of the best experts on this subject based on the ideXlab platform.

  • imatinib and chronic myeloid leukemia validating the promise of Molecularly Targeted Therapy
    European Journal of Cancer, 2002
    Co-Authors: Brian J Druker
    Abstract:

    The Bcr-Abl tyrosine kinase inhibitor imatinib (Glivec®, formerly STI571, Novartis Pharma AG, Basel, Switzerland) produces complete hematologic and cytogenetic responses in a substantial percentage of chronic myeloid leukemia patients. Imatinib is effective in chronic phase, accelerated phase and blast crisis, with lower response rates in patients with more advanced disease. Although responses have been durable in chronic phase patients, relapses have been common in blast crisis. Relapse has been associated with reactivation of Bcr-Abl kinase activity. The clinical development of imatinib illustrates the effectiveness of targeting molecular pathogenetic events. Hopefully, this example can be extended to other malignancies.

  • Perspectives on the development of a Molecularly Targeted agent
    Cancer Cell, 2002
    Co-Authors: Brian J Druker
    Abstract:

    Abstract STI571 (Gleevec, imatinib mesylate) exemplifies the successful development of a rationally designed, Molecularly Targeted Therapy for the treatment of a specific cancer. This article reviews the identification of Bcr-Abl as a therapeutic target in chronic myelogenous leukemia and the steps in the development of an agent to specifically inactivate this abnormality. Issues related to clinical trials of Molecularly Targeted agents are discussed, including dose and patient selection, as are possible mechanisms of resistance to STI571. Lastly, the potential use of STI571 in other malignancies and the translation of this paradigm to other malignancies is explored.

  • sti571 a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia validating the promise of Molecularly Targeted Therapy
    Cancer Chemotherapy and Pharmacology, 2001
    Co-Authors: Michael J Mauro, Michael Odwyer, Brian J Druker
    Abstract:

    The deregulated tyrosine kinase activity of the Bcr-Abl fusion protein has been established as the causative molecular event in chronic myelogenous leukemia (CML). Thus the Bcr-Abl tyrosine kinase is an ideal target for pharmacologic inhibition. STI571 (formerly CGP57148B), is an Abl-specific tyrosine kinase inhibitor that in preclinical studies selectively kills Bcr-Abl-containing cells in vitro and in vivo. The results of clinical studies have demonstrated the potential of Molecularly Targeted therapies, and STI571 is emerging as a new therapeutic agent for CML.

Keith T Flaherty - One of the best experts on this subject based on the ideXlab platform.

  • the intersection of immune directed and Molecularly Targeted Therapy in advanced melanoma where we have been are and will be
    Clinical Cancer Research, 2013
    Co-Authors: Ryan J. Sullivan, Patricia Lorusso, Keith T Flaherty
    Abstract:

    In three years, four drugs have gained regulatory approval for the treatment of metastatic and unresectable melanoma, with at least seven other drugs having recently completed, currently in, or soon to be in phase III clinical testing. This amazing achievement has been made following a remarkable increase of knowledge in molecular biology and immunology that led to the identification of high-valued therapeutic targets and the clinical development of agents that effectively engage and inhibit these targets. The discovery of either effective Molecularly Targeted therapies or immunotherapies would have led to dramatic improvements to the standard-of-care treatment of melanoma. However, through parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP-ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280), an opportunity exists to transform the treatment of melanoma specifically and cancer generally by exploring rational combinations of Molecularly Targeted therapies, immunotherapies, and molecular Targeted therapies with immunotherapies. This overview presents the historical context to this therapeutic revolution, reviews the benefits and limitations of current therapies, and provides a look ahead at where the field is headed.

  • clinical effect and future considerations for Molecularly Targeted Therapy in renal cell carcinoma
    Urologic Oncology-seminars and Original Investigations, 2008
    Co-Authors: Brian I Rini, Keith T Flaherty
    Abstract:

    Vascular endothelial growth factor (VEGF) pathway activation leads to the angiogenic phenotype of renal cell carcinoma (RCC). Several different strategies targeting various aspects of this pathway have emerged as standard Therapy in metastatic RCC. Bevacizumab, a VEGF ligand-binding antibody, sunitinib and sorafenib, small molecule inhibitors of the VEGF receptor, as well as temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR) have all shown substantial clinical activity in metastatic RCC. Several relevant clinical aspects have also emerged with use of these agents such as defining resistance, measurement of response, and combination Therapy.

  • seminar article clinical effect and future considerations for Molecularly Targeted Therapy in renal cell carcinoma
    2008
    Co-Authors: Brian I Rini, Keith T Flaherty
    Abstract:

    Vascular endothelial growth factor (VEGF) pathway activation leads to the angiogenic phenotype of renal cell carcinoma (RCC). Several different strategies targeting various aspects of this pathway have emerged as standard Therapy in metastatic RCC. Bevacizumab, a VEGF ligand-binding antibody, sunitinib and sorafenib, small molecule inhibitors of the VEGF receptor, as well as temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR) have all shown substantial clinical activity in metastatic RCC. Several relevant clinical aspects have also emerged with use of these agents such as defining resistance, measurement of response, and combination Therapy. © 2008

Kazuhisa Takahashi - One of the best experts on this subject based on the ideXlab platform.

  • Resistance to Molecularly Targeted Therapy in non-small-cell lung cancer.
    Respiratory investigation, 2018
    Co-Authors: Tetsuhiko Asao, Fumiyuki Takahashi, Kazuhisa Takahashi
    Abstract:

    Abstract The discovery of oncogenic driver gene mutations, including epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, and ret proto-oncogene (RET) fusion, has led to the development of Molecularly Targeted Therapy for non-small-cell lung cancer (NSCLC). This Therapy has changed the standard of care for NSCLC. Despite the dramatic response to Molecularly Targeted Therapy, almost all patients ultimately develop resistance to the drugs. To understand the mechanisms of resistance to Molecularly Targeted agents, it is essential to understand the molecular pathways of NSCLC. Here, we review the mechanisms of resistance to Molecularly Targeted Therapy and discuss strategies to overcome drug resistance.

Robert Nakayama - One of the best experts on this subject based on the ideXlab platform.

  • clinical characteristics and treatment outcomes in six cases of malignant tenosynovial giant cell tumor initial experience of Molecularly Targeted Therapy
    BMC Cancer, 2018
    Co-Authors: Robert Nakayama, Jyothi Priya Jagannathan, Nikhil Ramaiya, Marco L. Ferrone, Chandrajit P. Raut, John E. Ready, Jason L. Hornick, Andrew J. Wagner
    Abstract:

    Although tenosynovial giant cell tumor (TGCT) is classified as a benign tumor, it may undergo malignant transformation and metastasize in extremely rare occasions. High aberrant expression of CSF1 has been implicated in the development of TGCT and recent studies have shown promising activity of several CSF1R inhibitors against benign diffuse-type TGCT; however, little is known about their effects in malignant TGCT. Information from six consenting patients (3 men, 3 women) with malignant TGCT presenting to Dana-Farber Cancer Institute for initial or subsequent consultation was collected. Median age at initial diagnosis of TGCT was 49.5 years (range 12–55), and median age at diagnosis of malignant TGCT was 50 years (range 34–55). Two patients developed malignant TGCT de novo, while four other cases showed metachronous malignant transformation. All tumors arose in the lower extremities (3 knee, 2 thigh, 1 hip). Five patients underwent surgery for the primary tumors, and four developed local recurrence. All six patients developed lung metastases, and four of five evaluable tumors developed inguinal and pelvic lymph node metastases. All six patients received systemic Therapy. Five patients were treated with at least one tyrosine kinase inhibitor with inhibitory activity against CSF1R; however, only one patient showed clinical benefit (SD or PR). Five patients were treated with conventional cytotoxic agents. Doxorubicin-based treatment showed clinical benefit in all four evaluable patients, and gemcitabine/docetaxel showed clinical benefit in two patients. All six patients died of disease after a median of 21.5 months from diagnosis of malignant TGCT. This study confirms that TGCT may transform into an aggressive malignant tumor. Lymph node and pulmonary metastases are common. Local recurrence rates are exceedingly high. Conventional cytotoxic chemoTherapy showed clinical benefit, whereas tyrosine kinase inhibitors against CSF1R showed limited activity. Given its rarity, a prospective registry of malignant TGCT patients is needed to further understand the entity and to develop effective strategies for systemic treatment.

  • Clinical characteristics and treatment outcomes in six cases of malignant tenosynovial giant cell tumor: initial experience of Molecularly Targeted Therapy
    BMC, 2018
    Co-Authors: Robert Nakayama, Jyothi Priya Jagannathan, Nikhil Ramaiya, Marco L. Ferrone, Chandrajit P. Raut, John E. Ready, Jason L. Hornick, Andrew J. Wagner
    Abstract:

    Abstract Background Although tenosynovial giant cell tumor (TGCT) is classified as a benign tumor, it may undergo malignant transformation and metastasize in extremely rare occasions. High aberrant expression of CSF1 has been implicated in the development of TGCT and recent studies have shown promising activity of several CSF1R inhibitors against benign diffuse-type TGCT; however, little is known about their effects in malignant TGCT. Case presentation Information from six consenting patients (3 men, 3 women) with malignant TGCT presenting to Dana-Farber Cancer Institute for initial or subsequent consultation was collected. Median age at initial diagnosis of TGCT was 49.5 years (range 12–55), and median age at diagnosis of malignant TGCT was 50 years (range 34–55). Two patients developed malignant TGCT de novo, while four other cases showed metachronous malignant transformation. All tumors arose in the lower extremities (3 knee, 2 thigh, 1 hip). Five patients underwent surgery for the primary tumors, and four developed local recurrence. All six patients developed lung metastases, and four of five evaluable tumors developed inguinal and pelvic lymph node metastases. All six patients received systemic Therapy. Five patients were treated with at least one tyrosine kinase inhibitor with inhibitory activity against CSF1R; however, only one patient showed clinical benefit (SD or PR). Five patients were treated with conventional cytotoxic agents. Doxorubicin-based treatment showed clinical benefit in all four evaluable patients, and gemcitabine/docetaxel showed clinical benefit in two patients. All six patients died of disease after a median of 21.5 months from diagnosis of malignant TGCT. Conclusions This study confirms that TGCT may transform into an aggressive malignant tumor. Lymph node and pulmonary metastases are common. Local recurrence rates are exceedingly high. Conventional cytotoxic chemoTherapy showed clinical benefit, whereas tyrosine kinase inhibitors against CSF1R showed limited activity. Given its rarity, a prospective registry of malignant TGCT patients is needed to further understand the entity and to develop effective strategies for systemic treatment