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1.  Assessing tumor response after loco-regional liver cancer therapies: the role of 3D MRI 
Assessing the tumor response of liver cancer lesions after intraarterial therapies is of major clinical interest. Over the last two decades, tumor response criteria have come a long way from purely size-based, anatomic methods such as the Response Evaluation Criteria in Solid Tumors towards more functional, enhancement- and diffusion-based parameters with a strong emphasis on MRI as the ultimate imaging modality. However, the relatively low reproducibility of those one- and 2D techniques (modified Response Evaluation Criteria in Solid Tumors and the European Association for the Study of the Liver criteria) provided the rationale for the development of new, 3D quantitative assessment techniques. This review will summarize and compare the existing methodologies used for 3D quantitative tumor analysis and provide an overview of the published clinical evidence for the benefits of 3D quantitative tumor response assessment techniques.
PMCID: PMC4304995  PMID: 25371052
3D; ADC; intraarterial therapy; liver cancer; MRI; qEASL; quantitative imaging; RECIST; tumor response
2.  Towards personalized therapy for patients with glioblastoma 
Expert review of anticancer therapy  2011;11(12):1935-1944.
Combined therapy with temozolomide and radiotherapy is a standard treatment and improves the survival for patients with newly diagnosed glioblastoma. However, the prognosis remains poor, with a median survival time of 12–15 months. Currently, several clinical trials of dose-dense temozolomide regimen or molecular-targeting therapies have been performed to overcome the resistance of glioblastoma. In these therapies, rational prognostic biomarkers have also been investigated to predict their outcome and response to treatment. This advanced understanding of the biological markers can help to develop personalized therapies for glioblastoma patients. Generally, due to a reduced tolerance, elderly patients do not seem to benefit from intensive treatment. This population needs individual treatments depended on their age or performance status. In this article, we review the recent studies that can provide personalized therapy for glioblastoma, based on molecular tumor profiling or patients’ physical status.
PMCID: PMC4297206  PMID: 22117160
elderly patients; glioblastoma; MGMT; personalized therapy; radiotherapy; targeting therapy; temozolomide
3.  [No title available] 
PMCID: PMC4289602  PMID: 24930453
4.  Chemoselection: A Paradigm for Optimization of Organ Preservation in Locally Advanced Larynx Cancer 
Expert review of anticancer therapy  2013;13(9):1053-1064.
Definitive chemoradiation (CRT) and laryngectomy followed by postoperative radiotherapy (RT) are both considered standard of care options for the management of advanced laryngeal cancer. While organ preservation with chemoradiotherapy is often the preferred up-front approach for appropriately selected candidates, the functional benefits of organ preservation must be carefully balanced against the considerable morbidity of salvage laryngectomy in patients who fail primary chemoradiation. Up-front identification of patients who are likely to require surgical salvage, therefore, is an important aim of any organ preserving approach in order to minimize morbidity while maximizing organ preservation. To this end, a strategy of “chemoselection”, using the primary tumor's response after one cycle of induction chemotherapy as an in vivo method of selecting responders for definitive chemoradiation while reserving primary surgical management for non-responders, has been employed extensively at our institution. The rationale, treatment results, and future directions of this approach are discussed.
PMCID: PMC4264982  PMID: 24053204
Larynx preservation; chemoselection; induction chemotherapy; concurrent chemoradiation; salvage laryngectomy
5.  Tyrosine kinase inhibition: A therapeutic target for the management of chronic-phase chronic myeloid leukemia 
Expert review of anticancer therapy  2013;13(12):1433-1452.
Chronic myeloid leukemia (CML) is a hematologic neoplasm with a progressive, ultimately terminal, disease course. In most cases, CML arises owing to the aberrant formation of a chimeric gene for a constitutively active tyrosine kinase. Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target transforming the prognosis of patients with CML. New tyrosine kinase inhibitors (TKIs) continue to improve the management of CML, offering alternative options for those resistant to or intolerant of standard TKIs. Here we review the pathobiology of CML and explore emerging strategies to optimize the management of chronic-phase CML, particularly first-line treatment.
PMCID: PMC4181370  PMID: 24236822
tyrosine kinase inhibition; chronic myeloid leukemia; molecular response; suboptimal response
6.  Chronic lymphocytic leukemia: planning for an aging population 
Expert review of anticancer therapy  2010;10(9):1389-1394.
Chronic lymphocytic leukemia (CLL) remains incurable, but over the past decade there have been major advances in the understanding of the pathophysiology of CLL and in the treatment of this disease. This has led to greatly increased response rates and durations of response, as well as improved survival. CLL is a disease of the elderly and not all patients are eligible for the aggressive upfront chemoimmunotherapy regimens that are resulting in improved response rates and survival, so what is the optimal treatment approach for more frail elderly patients? It is highly likely that our treatment approaches will continue to evolve as the results of ongoing clinical trials are released. The age range of patients involved in clinical trials is not representative of this disease, and more research is required in patients who are representative of the majority of CLL patients seen in practice before we will see outcome improvements in these more elderly and often more frail patient populations.
PMCID: PMC4241366  PMID: 20836674
chronic lymphocytic leukemia; clinical trials; comorbidity; elderly; treatment
8.  Pancreatic cancer: current standards, working towards a new therapeutic approach 
Pancreatic cancer is the fourth leading cause of cancer deaths with a 5-year survival of 4–6%. Clinical challenges remain to be addressed, since few promising approaches to treat pancreatic cancer have been reported. Here we discuss the potential of a new biotherapeutic agent composed of a lysosomal protein (Saposin C, SapC) and an acidic phospholipid (dioleoylphosphatidylserine, DOPS) which can be assembled into stable nanovesicles (SapC-DOPS) for tackling pancreatic cancer. Phosphatidylserine (PS) is a lipid biomarker on membrane surface of pancreatic cancer cells and can be effectively targeted by SapC-DOPS nanovesicles for cancer-selective therapy. SapC-DOPS nanovesicles have shown excellent pre-clinical therapeutic and safety profiles. Safety profiles which suggests that this new approach is potentially a viable option for pancreatic cancer therapy that is worthy of further clinical development.
PMCID: PMC4086873  PMID: 24621210
chemotherapy; combination treatment; metastases; monotherapy; new approach; pancreatic cancer therapy; resistance; SapC-DOPS nanovesicles; toxicity
9.  Potential of optical coherence tomography for early diagnosis of oral malignancies 
With nearly 1,500,000 new patients diagnosed every year in the USA, cancer poses a considerable challenge to healthcare today. Oral cancer is responsible for a sizeable portion of deaths due to cancer, primarily because it is diagnosed at a late stage when the prognosis is poor. Current methods for diagnosing oral cancer need to be augmented by better early detection, monitoring and screening modalities. A new approach is needed that provides real-time, accurate, noninvasive diagnosis. The results of early clinical trials using in vivo optical coherence tomography for the diagnosis of oral dysplasia and malignancy are encouraging.
PMCID: PMC4038412  PMID: 20214513
early detection; gold nanoparticles; noninvasive diagnostics; optical coherence tomography; oral cancer
10.  Targeted therapy for non-small-cell lung cancer: past, present and future 
Therapy for advanced non-small-cell lung cancer has developed significantly with new awareness of histologic subtype as an important factor in guiding treatment and the development of targeted agents for molecular subgroups harboring critical mutations that spur on cancer growth. In this comprehensive review, we look back at developments in targeted therapy for advanced non-small-cell lung cancer, reviewing in detail efforts, both successful and in some cases less so, to target EGFR, VEGF and ALK. This review provides an overview of where the field stands at present and the areas we feel are most likely to provide challenges and potential successes in the next 5 years including immune checkpoint inhibition, epigenetic therapy and driver mutation targeting.
PMCID: PMC3991462  PMID: 23773106
ALK; crizotinib; EGFR; epigenetic; erlotinib; immune checkpoint; non-small-cell lung cancer; PD1; targeted therapy; VEGF
12.  Endotrophin in the tumor stroma: a new therapeutic target for breast cancer? 
PMCID: PMC3732472  PMID: 23406549
Adipocyte; Breast cancer; Endotrophin; Microenvironment; Chemoresistance
13.  Challenges in the long-term management of patients with metastatic renal cell carcinoma treated with targeted therapy: Optimizing surgery, systemic therapy and quality of life 
Expert review of anticancer therapy  2010;10(12):1883-1889.
Therapy for patients with metastatic renal cell carcinoma is becoming increasingly effective. Sustained partial remissions, occasional complete responses, and manageable quality of life are seen in a subset of individuals. As we face the prospect of generating an increasingly large number of patients requiring long-term management, the choice and timing of systemic therapy and surgical interventions is becoming increasingly important. In this paper, we review the timing and type of cytoreductive nephrectomy, what to do for patients with oligometastatic disease, and how to deal with complete responders. In addition, we summarize the major side effects experienced with the commonly used molecularly targeted agents, and provide guidance on how to maximize benefit from these agents while maintaining an acceptable quality of life for patients. As treatment efficacy improves, the optimal integration of systemic therapy, surgery and toxicity management will become a critical aspect of our care for patients with mRCC.
PMCID: PMC3895462  PMID: 21110755
renal cell carcinoma; targeted therapy; cancer survivorship; therapy complications
14.  Protein Kinase D isoforms – New targets for therapy in invasive Breast Cancers? 
Expert review of anticancer therapy  2013;13(8):10.1586/14737140.2013.816460.
The Protein Kinase D (PKD) family of serine/threonine kinases consists of three members-PKD1, PKD2, and PKD3. While PKD1 in many cancers has been identified as a suppressor of the invasive phenotype, the two other PKD subtypes, PKD2 and PKD3, have been attributed oncogenic functions. In invasive Breast Cancer cells PKD1 expression is downregulated by methylation of the PRKD1 promoter. On the other hand, PKD2 and PKD3 are not silenced, and drive proliferation, invasion, and mediate chemoresistance. Two strategies emerge to utilize this knowledge for novel treatment opportunities. First, pan PKD inhibitors could be developed and used for these aggressive cancers. An alternative approach to obtain similar effects would be to induce the re-expression of PKD1.
PMCID: PMC3856925  PMID: 23944680
Protein Kinase D; PKD; isoforms; breast cancer; therapy
15.  Heat-shock protein vaccines as active immunotherapy against human gliomas 
Expert review of anticancer therapy  2009;9(11):10.1586/era.09.104.
Modern advances in cancer immunotherapy have led to the development of active immunotherapy that utilizes tumor-associated antigens to induce a specific immune response against the tumor. Current methods of immunotherapy implementation are based on the principle that tumor-associated antigens are capable of being processed by antigen-presenting cells and inducing an activated cytotoxic T-lymphocyte-specific immune response that targets the tumor cells. Antigen internalization and processing by antigen-presenting cells, such as dendritic cells, or macrophages results in their surface association with MHC class I molecules, which can be recognized by an antigen-specific cytotoxic T-lymphocyte adaptive immune response. With the aim of augmenting current immunotherapeutic modalities, much effort has been directed towards enhancing antigen-presenting cell activation and optimizing the processing of tumor-associated antigens and major histocompatibility molecules. The goal of these immunotherapy modifications is to ultimately improve the adaptive specific immune response in killing of tumor cells while sparing normal tissues. Immunotherapy has been actively studied and applied in glioblastomas. Preclinical animal models have shown the feasibility of an active immunotherapy approach through the utilization of tumor vaccines, and recently several clinical studies have also been initiated. Recently, endogenous heat-shock proteins have been implicated in the mediation of both the adaptive and innate immune responses. They are now being investigated as a potential modality and adjuvant to immunotherapy, and they represent a promising novel treatment for human glioblastomas.
PMCID: PMC3836274  PMID: 19895242
active immune response; antigen; antigen-presenting cells; cancer vaccines; CTL; heat-shock proteins; immunotherapy; T-cell lymphocytes
16.  Targeting the alternative NF-κB pathway in pancreatic cancer: a new direction for therapy? 
Pancreatic cancer, due to its late diagnosis, is difficult to treat. In addition, current therapy options are insufficient and new approaches for combination treatment are required. Recent demonstration of the importance of constitutive signaling of NF-κB-inducing kinase (NIK, also named MAP3K14) in maintaining the high basal activity of the alternative NF-κB pathway in pancreatic cancer suggests novel possibilities for therapeutic intervention. Strategies to target the alternative NF-κB pathway include not only the use of small molecule inhibitors for NIK and IκB kinase α (IKKα), but also broad spectrum approaches such as using proteasome inhibitors or combinatorial approaches targeting both alternative and canonical pathways. These may also act synergistically with currently used drugs.
PMCID: PMC3800143  PMID: 23617340
alternative; MAP3K14; NF-κB; NIK; noncanonical; pancreatic cancer; therapy; TRAF2
17.  Potential of whole-genome sequencing for determining risk and personalizing therapy: focus on AML 
Expert review of anticancer therapy  2012;12(10):1289-1297.
In spite of recent advances in molecular diagnostic techniques and expanded indications for allogeneic hematopoietic stem cell transplantation, treatment of acute myeloid leukemia (AML) remains a major challenge. In the last decade, several recurrent genetic abnormalities and gene mutations with prognostic implications have been identified. This has led to improved informed treatment decisions. However, there has been limited change in the use of nonspecific cytotoxic chemotherapy and mortality rates continue to be unacceptably high, with 5 year overall survival rates of older AML patients at 30% or less. Whole-genome sequencing offers hope for greater diagnostic accuracy and is likely to lead to further characterization of disease subsets with differential outcome and response to treatment. The holy grail of personalized targeted therapy for the individual AML patient, while minimizing toxicity and prolonging survival, appears closer than ever.
PMCID: PMC3636990  PMID: 23176617
acute myeloid leukemia; FLT3 mutation; normal karyotype; outcome; PCR; personalized therapy; prognostic factors; treatment; whole-genome sequencing
18.  Current role of EGF receptor monoclonal antibodies and tyrosine kinase inhibitors in the management of head and neck squamous cell carcinoma 
Expert review of anticancer therapy  2012;12(9):1149-1159.
New agents and treatment strategies that can be safely and effectively integrated into current treatment paradigms for head and neck squamous cell carcinoma (HNSCC) are urgently needed. To date, the anti-EGF receptor (EGFR) monoclonal antibody, cetuximab, is the first and only molecularly targeted therapy to demonstrate a survival benefit for patients with recurrent or metastatic disease. Other anti-EGFR-targeted therapies, including monoclonal antibodies (e.g., panitumumab and zalutumumab) and reversible and irreversible ErbB family tyrosine kinase inhibitors (e.g., lapatinib, afatinib and dacomitinib) are being actively investigated in Phase II and Phase III clinical trials. In addition, validated biomarkers are needed to predict clinical benefit and resistance to anti-EGFR therapy in HNSCC. This review will compare and contrast the mechanisms of action of anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors and also discuss their role in the management of HNSCC and the potential impact of human papillomavirus status in the development of these targeted agents.
PMCID: PMC3715045  PMID: 23098115
epidermal growth factor receptor; head and neck squamous cell carcinoma; HER tyrosine kinase receptor family; therapeutic monoclonal antibody; tyrosine kinase inhibitor
19.  Identifying the risk factors for late stage head and neck cancer 
Expert review of anticancer therapy  2011;11(9):1321-1325.
PMCID: PMC3715314  PMID: 21929305
Locoregionally advanced stage III or stage IV cancers; molecular modeling; diagnostic markers; tumor tissue-cancer models; multi-ethnic cohorts; disparities; African American; Caucasian American; human papilloma virus
20.  Novel strategies for treating relapsed/refractory urothelial carcinoma 
Expert review of anticancer therapy  2010;10(12):1917-1932.
Advanced urothelial cancer is associated with a poor prognosis and there has been no substantial progress over the past three decades since the development of platinum-based multiagent chemotherapy. Clinical trials evaluating novel agents and combinations including chemotherapeutic drugs, as well as targeted inhibitors, are desperately needed. With a better understanding of the complex molecular alterations that drive urothelial tumorigenesis, new targets for novel therapeutics are being defined. This article will describe the current state of advanced urothelial cancer treatment and provide a comprehensive discussion of novel agents in development.
PMCID: PMC3705930  PMID: 21110758
bladder cancer; targeted therapy; transitional cell carcinoma; urothelial cancer
21.  Autophagy and endocrine resistance in breast cancer 
Expert review of anticancer therapy  2011;11(8):1283-1294.
The American Cancer Society estimates that over 200,000 new breast cancer cases are diagnosed annually in the USA alone. Of these cases, the majority are invasive breast cancers and almost 70% are estrogen receptor-α positive. Therapies targeting the estrogen receptor-α are widely applied and include selective estrogen receptor modulators such as tamoxifen, a selective estrogen receptor downregulator such as Fulvestrant (Faslodex; FAS, ICI 182,780), or one of the third-generation aromatase inhibitors including letrozole or anastrozole. While these treatments reduce breast cancer mortality, many estrogen receptor-α-positive tumors eventually recur, highlighting the clinical significance of endocrine therapy resistance. The signaling leading to endocrine therapy resistance is poorly understood; however, preclinical studies have established an important role for autophagy in the acquired resistance phenotype. Autophagy is a cellular degradation process initiated in response to stress or nutrient deprivation, which attempts to restore metabolic homeostasis through the catabolic lysis of aggregated proteins, unfolded/misfolded proteins or damaged subcellular organelles. The duality of autophagy, which can be either pro-survival or pro-death, is well known. However, in the context of endocrine therapy resistance in breast cancer, the inhibition of autophagy can potentiate resensitization of previously antiestrogen resistant breast cancer cells. In this article, we discuss the complex and occasionally contradictory roles of autophagy in cancer and in resistance to endocrine therapies in breast cancer.
PMCID: PMC3701722  PMID: 21916582
3-methyladenine; antiestrogen resistance; aromatase inhibitor; autophagy; bafilomycin A1; breast cancer; endoplasmic reticulum stress; fulvestrant; hydroxychloroquine; tamoxifen; unfolded protein response
22.  New vitamin D analogs as potential therapeutics in melanoma 
Extensive evidence shows that the active form of vitamin D3 – 1α,25-dihydroxyvitamin D3 – plays an important role in cancer prevention, has tumorostatic activity and may potentially be used in therapy for melanoma. Vitamin D3 and its analogs (secosteroids) exert multiple effects on cancer cells, including inhibition of cell growth and induction of differentiation. Activity of secosteroids depends on multiple cellular factors, including expression of the vitamin D receptor. Despite its endogenous origin, the key drawback for the use of pharmacologically effective doses of 1α,25-dihydroxyvitamin D3 is its hypercalcemic effect leading to profound toxicity. The solution may lie in properties of vitamin D3 analogs with modified side chains, which demonstrate low calcemic activity but conserve the anti-tumor properties. Noncalcemic vitamin D compounds were found to be potent in multiple studies that mandate further clinical testing. Finally, recent studies revealed alternative metabolic pathways for secosteroids and new targets in the cells, which opens up new therapeutic possibilities.
PMCID: PMC3368500  PMID: 22594894
1α,25-dihydroxyvitamin D3; melanoma; secosteroids; VDR; vitamin D; vitamin D analogs; vitamin D receptor
23.  Contemporary management of muscle-invasive bladder cancer 
The current standard treatment for muscle-invasive nonmetastatic bladder cancer is neoadjuvant platinum-based chemotherapy followed by radical cystectomy. However, neoadjuvant chemotherapy is not widely accepted even with level 1 evidence. Adjuvant chemotherapy should be discussed if patients have not received neoadjuvant chemotherapy before surgery and have high-risk pathologic features. Although not considered standard of care, bladder-sparing therapy can be considered for highly selected patients and for those medically unfit for surgery. Even though there are no level 1 data, the treatment outcomes for highly select patients given bladder-sparing therapy appear promising, with many patients retaining a functional bladder. Personalized chemotherapy is currently being actively pursued to target the underlying molecular changes and tailor to individual needs.
PMCID: PMC3494992  PMID: 22845409
bladder urothelial carcinoma; chemotherapy; cisplatin; personalized chemotherapy; targeted therapy
24.  The Role of Chemoradiation for Patients with Resectable or Potentially Resectable Pancreatic Cancer 
Conflicting data and substantial controversy exist regarding optimal adjuvant treatment for those patients with resectable or potentially resectable adenocarcinoma of the pancreas. Despite improvements in short-term surgical outcomes, the use of newer chemotherapeutic agents, development of targeted agents, and more precise delivery of radiation, the 5-year survival rates for early stage patients remains less than 25%. This article critically reviews the existing data for various adjuvant treatment approaches for patients with surgically resectable pancreatic cancer. Our review confirms that despite several randomized clinical trials, the optimal adjuvant treatment approach for these patients remains unclear.
Despite improvements in short-term surgical outcomes, use of newer chemotherapeutic agents, development of targeted agents, and more precise delivery of radiation, the 5-year survival rates for early stage patients remains less than 25%. Despite several randomized clinical trials in these patients, the optimal treatment approach remains unclear. We review data the data regarding adjuvant therapy for patients with early stage pancreas cancer and discuss potential tumor factors that can be used to select patients for optimal adjuvant therapy. The probability of long-term survival is higher in patients who undergo margin-negative resections but local and distant failures are common, indicating the need for adjuvant therapies. Improved systemic treatment is desperately needed and the role of adjuvant radiation remains unclear. Neoadjuvant chemoradiation is being studied as an alternative to postoperative therapy. Potential molecular targets have been identified and the benefit of the addition of biologic agents to adjuvant treatments is being explored.
PMCID: PMC3628691  PMID: 22500684
Pancreatic Adenocarcinoma; Radiotherapy; Combined Modality Therapy; Biological Markers; Molecular Targets; Neoadjuvant
25.  Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade 
Expert review of anticancer therapy  2012;12(12):1597-1611.
Breast cancer is immunogenic, and infiltrating immune cells in primary breast tumors convey important clinical prognostic and predictive information. Furthermore, the immune system is critically involved in clinical responses to some standard cancer therapies. Early breast cancer vaccine trials have established the safety and bioactivity of breast cancer immunotherapy, with hints of clinical activity. Novel strategies for modulating regulators of immunity, including regulatory T cells, myeloid-derived suppressor cells and immune checkpoint pathways (monoclonal antibodies specific for the cytotoxic T-lymphocyte antigen-4 or programmed death), are now available. In particular, immune checkpoint blockade has enormous therapeutic potential. Integrative breast cancer immunotherapies that strategically combine established breast cancer therapies with breast cancer vaccines, immune checkpoint blockade or both should result in durable clinical responses and increased cures.
PMCID: PMC3587160  PMID: 23253225
breast cancer immunity; breast cancer vaccine; clinical trials; immune checkpoint blockade; immune tolerance; immunotherapy; tumor microenvironment

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