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Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application
The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC. Unfortunately, drug resist...
Source: Therapeutic Advances in Medical Oncology - August 20, 2015 Category: Cancer & Oncology Authors: Maione, P., Sacco, P. C., Sgambato, A., Casaluce, F., Rossi, A., Gridelli, C. Tags: Reviews Source Type: research

Precision medicine in colorectal cancer: the molecular profile alters treatment strategies
When considering treatment options for patients with metastatic colorectal cancer (mCRC), molecular profiling has become a pivotal component in guiding clinical decisions. FOLFOX and FOLFIRI (fluorouracuil, leucovorin plus oxaliplatin or ininotecan, respectively) are the standard base regimens used for the treatment of mCRC. Biologic agents, such as the epidermal growth factor receptor (EGFR) targeted therapies, cetuximab and panitumumab and the vascular endothelial growth factor monoclonal antibody, bevacizumab, are safe and effective in the first-line setting. The most efficacious use of these agents in terms of timing a...
Source: Therapeutic Advances in Medical Oncology - August 20, 2015 Category: Cancer & Oncology Authors: Tran, N. H., Cavalcante, L. L., Lubner, S. J., Mulkerin, D. L., LoConte, N. K., Clipson, L., Matkowskyj, K. A., Deming, D. A. Tags: Reviews Source Type: research

Chemotherapy use in stage III colon cancer: a National Cancer Database analysis
Conclusion: More than one-third did not receive adjuvant chemotherapy, although its use has increased in more recent years. Age was one of the most important determinants of chemotherapy use, which may explain higher rates in nonwhite and uninsured. In addition to patient characteristics, race, gender and socioeconomic factors influence chemotherapy use. These findings have important implications for healthcare reform. (Source: Therapeutic Advances in Medical Oncology)
Source: Therapeutic Advances in Medical Oncology - August 20, 2015 Category: Cancer & Oncology Authors: Upadhyay, S., Dahal, S., Bhatt, V. R., Khanal, N., Silberstein, P. T. Tags: Original Research Source Type: research

Corrigendum
Stinchcombe, T. (2014) Novel agents in development for advanced non-small cell lung cancer. Ther Adv Med Oncol 6(5): 240–253. In the sentence on page 246, the subset analysis of patients with adenocarcinoma histology comprised 658 patients and not 568, as stated. (Source: Therapeutic Advances in Medical Oncology)
Source: Therapeutic Advances in Medical Oncology - June 15, 2015 Category: Cancer & Oncology Tags: Corrigendum Source Type: research

Combination capecitabine and bevacizumab in the treatment of metastatic hepatic epithelioid hemangioendothelioma
We present a diagnostically challenging case of HEHE where we utilized capecitabine and bevacizumab as another novel treatment option. (Source: Therapeutic Advances in Medical Oncology)
Source: Therapeutic Advances in Medical Oncology - June 15, 2015 Category: Cancer & Oncology Authors: Lau, A., Malangone, S., Green, M., Badari, A., Clarke, K., Elquza, E. Tags: Reviews Source Type: research

Bone-targeted agents in the treatment of lung cancer
Over a third of patients with lung cancer will develop bone metastases during the course of their disease, resulting in symptoms of pain and immobility, and skeletal-related events (SREs) such as fracture, hypercalcaemia, surgery or radiotherapy to bones, and malignant spinal cord compression. These reduce quality of life and increase mortality. Preclinical research has identified the interactions between tumour cells and bone that are key to tumour cell survival and associated osteolysis. These data have led to the development of drugs to prevent osteoclast-mediated bone breakdown, such as zoledronic acid and denosumab, w...
Source: Therapeutic Advances in Medical Oncology - June 15, 2015 Category: Cancer & Oncology Authors: Silva, S. C., Wilson, C., Woll, P. J. Tags: Reviews Source Type: research

Vintafolide: a novel targeted therapy for the treatment of folate receptor expressing tumors
Despite advances in the development of molecularly targeted therapies, limited improvements in overall survival have been noted among many cancer patients with solid tumors, primarily due to development of drug resistance. Accordingly, there is an unmet need for new targeted therapies and treatment approaches for cancer, especially for overcoming resistance. Expression of the folate receptor is upregulated in many tumor types and thus represents an ideal target for cancer treatment. Several folate receptor targeted therapies are in development, including the small molecule drug conjugate vintafolide, the monoclonal antibod...
Source: Therapeutic Advances in Medical Oncology - June 15, 2015 Category: Cancer & Oncology Authors: Vergote, I., Leamon, C. P. Tags: Reviews Source Type: research

Systemic therapy in stage IV pancreatic cancer: a population-based analysis using the National Cancer Data Base
Conclusions: This is the largest study to evaluate the determinants of systemic therapy use in stage IV pancreatic cancer. The use of systemic therapy was significantly lower in patients older than 40 years, lower educational status, nonprivate insurance and with higher Charlson Comorbidity Scores. In addition, the use of systemic therapy was lower with female sex, African Americans/Hispanic, and lower socio-economic status. Understanding the barriers in the use of systemic therapy as well as appropriate utilization of systemic therapy can both optimize cancer care. (Source: Therapeutic Advances in Medical Oncology)
Source: Therapeutic Advances in Medical Oncology - June 15, 2015 Category: Cancer & Oncology Authors: Khanal, N., Upadhyay, S., Dahal, S., Bhatt, V. R., Silberstein, P. T. Tags: Original Research Source Type: research

Long-term survival as a treatment benchmark in melanoma: latest results and clinical implications
Historically, stage III–IV melanoma patients have had few options to achieve long-term survival. For patients with stage III disease, surgery alone may be curative for approximately 50%. Adjuvant treatment with a slightly greater impact on relapse-free survival at the cost of substantial toxicity, and studies are ongoing to test the adjuvant benefit of other immunotherapies that appear more active and less toxic in advanced melanoma. Achieving long term survival for stage IV patients had been rare until recently and progress was painfully slow with traditional cytotoxic chemotherapy; review of multiple phase II studi...
Source: Therapeutic Advances in Medical Oncology - April 15, 2015 Category: Cancer & Oncology Authors: Grossmann, K. F., Margolin, K. Tags: Reviews Source Type: research

MEK and PI3K inhibition in solid tumors: rationale and evidence to date
PI3K-AKT-mTOR and Ras-Raf-MEK-ERK are the most commonly altered oncogenic pathways in solid malignancies. There has been a lot of enthusiasm to develop inhibitors to these pathways for cancer therapy. Unfortunately, the antitumor activities of single-agent therapies have generally been disappointing, excluding B-Raf mutant melanoma and renal cell cancer. Preclinical studies have suggested that concurrent targeting of the PI3K-AKT-mTOR and Ras-Raf-MEK-ERK pathways is an active combination in various solid malignancies. In the current work, we review the preclinical data of the PI3K and MEK dual targeting as a cancer therapy...
Source: Therapeutic Advances in Medical Oncology - April 15, 2015 Category: Cancer & Oncology Authors: Jokinen, E., Koivunen, J. P. Tags: Reviews Source Type: research

Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review
Systemic therapy is the standard care for patients with unresectable advanced colorectal cancer (CRC), but salvage surgery of metastatic disease should be considered in the case of adequate tumor shrinkage. Several drugs and combinations are now available for use in treating patients with advanced CRC, but the optimal sequence of therapy remains unknown. Moreover, the administration of antitumor therapy can be modulated by periods of maintenance or treatment breaks rather than delivered as full therapy until disease progression or unacceptable toxicity, followed by reintroduction of prior full therapy when required, before...
Source: Therapeutic Advances in Medical Oncology - April 15, 2015 Category: Cancer & Oncology Authors: Chibaudel, B., Tournigand, C., Bonnetain, F., Richa, H., Benetkiewicz, M., Andre, T., de Gramont, A. Tags: Reviews Source Type: research

Relapse profile of early breast cancer according to immunohistochemical subtypes: guidance for patient's follow up?
Conclusion: The relapse risk in Tunisian patients is higher in young women and patients with HER2+ and TN tumors. A long and close follow up is recommended for patients with HR and HER2. Conversely, we suggest that follow up in patients with TN could be spaced after 4 years (ARR being <1.5% after this period). (Source: Therapeutic Advances in Medical Oncology)
Source: Therapeutic Advances in Medical Oncology - April 15, 2015 Category: Cancer & Oncology Authors: Mejri, N., Boussen, H., Labidi, S., Benna, F., Afrit, M., Rahal, K. Tags: Original Research Source Type: research

Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma
Following the discovery that nearly half of all cutaneous melanomas harbour a mutation in the BRAF gene, molecular targeted kinase inhibitors have been developed for the treatment of metastatic melanoma and have dramatically improved outcomes for those patients with BRAF mutant disease, achieving high levels of objective response and prolonging survival. Since 2011, the specific BRAF targeted agents, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have been licensed for the treatment of patients with unresectable or metastatic BRAF mutant melanoma. As with other biological targeted agents, these drugs are as...
Source: Therapeutic Advances in Medical Oncology - March 2, 2015 Category: Cancer & Oncology Authors: Welsh, S. J., Corrie, P. G. Tags: Reviews Source Type: research

Blinded by the light: why the treatment of metastatic melanoma has created a new paradigm for the management of cancer
Until recently, treatment for metastatic melanoma was characterised by a limited availability of treatment options that offer objective survival benefit. Cytotoxic agents fundamentally lack the ability to achieve disease control and cytokine therapy with interleukin-2 has an unacceptably high – for the use across all patient cohorts – rate of toxicities. The validation of braf as an oncogene driving melanoma tumorigenesis, as well as the discovery of the role of CTLA-4 receptor in the evasion of anticancer immune response by melanoma, has revolutionised our treatment options against a disease with dismal progno...
Source: Therapeutic Advances in Medical Oncology - March 2, 2015 Category: Cancer & Oncology Authors: Lindsay, C. R., Spiliopoulou, P., Waterston, A. Tags: Reviews Source Type: research

Nivolumab in melanoma: latest evidence and clinical potential
Melanoma has historically been considered a refractory disease with few if any options in the advanced/metastatic setting. Advances in both immune and genetically targeted treatment approaches have revolutionized the spectrum of treatment options for melanoma patients over the last several years. Recently, checkpoint inhibition has become a major focus in the immune-based therapy of cancer, especially melanoma. This concept involves inhibition of regulatory cell surface molecules which act normally to dampen or modulate T-cell activation. Cancer, including melanoma, takes advantage of this physiologic mechanism to turn off...
Source: Therapeutic Advances in Medical Oncology - March 2, 2015 Category: Cancer & Oncology Authors: Johnson, D. B., Peng, C., Sosman, J. A. Tags: Reviews Source Type: research