An update on adjuvant systemic therapies in melanoma

There is a global increase in the incidence of melanoma, with approximately 300,000 new cases in 2018 worldwide, according to statistics from the International Agency for Research on Cancer. With this rising incidence, it is important to optimize treatment strategies in all stages of the disease to provide better patient outcomes. The role of adjuvant therapy in patients with resected stage 3 melanoma is a rapidly evolving field. Interferon was the first agent shown to have any utility in this space, however, recent advances in both targeted therapies and immunotherapies have led to a number of practice changing adjuvant trials in resected stage 3 disease.

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Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer

Cancers ◽

10.3390/cancers13153892 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3892

Author(s):

Kaisa Lehtomäki ◽

Harri Mustonen ◽

Pirkko-Liisa Kellokumpu-Lehtinen ◽

Heikki Joensuu ◽

Kethe Hermunen ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Therapy ◽

Lead Time ◽

Disease Free Survival ◽

Phase Iii ◽

Lead Times ◽

Curative Intent ◽

Serum Cea ◽

Resected Stage

In colorectal cancer (CRC), 20–50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II–IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32–11.69); 3.72 (1.99–6.95); 2.58 (1.18–5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64–5.73); 3.41 (1.55–7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38–7.04) and OS, HR 3.20 (1.39–7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0–53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.

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Targeted Therapies for Pancreatic Cancer: Overview of Current Treatments and New Opportunities for Personalized Oncology

Cancers ◽

10.3390/cancers13040799 ◽

2021 ◽

Vol 13 (4) ◽

pp. 799 ◽

Cited By ~ 1

Author(s):

Cédric Leroux ◽

Georgia Konstantinidou

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Ductal Adenocarcinoma ◽

Patient Outcomes ◽

Targeted Therapies ◽

Median Overall Survival ◽

Advanced Disease ◽

Treatment Strategies ◽

Ductal Adenocarcinoma ◽

Cancer Associated Fibroblasts ◽

Personalized Oncology

Cytotoxic chemotherapy remains the only treatment option for most pancreatic ductal adenocarcinoma patients. Currently, the median overall survival of patients with advanced disease rarely exceeds 1 year. The complex network of pancreatic cancer composed of immune cells, endothelial cells, and cancer-associated fibroblasts confers intratumoral and intertumoral heterogeneity with distinct proliferative and metastatic propensity. This heterogeneity can explain why tumors do not behave uniformly and are able to escape therapy. The advance in technology of whole-genome sequencing has now provided the possibility of identifying every somatic mutation, copy-number change, and structural variant in a given cancer, giving rise to personalized targeted therapies. In this review, we provide an overview of the current and emerging treatment strategies in pancreatic cancer. By highlighting new paradigms in pancreatic ductal adenocarcinoma treatment, we hope to stimulate new thoughts for clinical trials aimed at improving patient outcomes.

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Role of adjuvant therapy in resected stage IA subcentimeter (T1a/T1b) pancreatic cancer

Cancer ◽

10.1002/cncr.31787 ◽

2018 ◽

Vol 125 (1) ◽

pp. 57-67 ◽

Cited By ~ 3

Author(s):

Walid L. Shaib ◽

Amit Surya Narayan ◽

Jeffrey M. Switchenko ◽

Sujata R. Kane ◽

Christina Wu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Stage Ia ◽

Resected Stage

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Roles of Gut-Derived Secretory Factors in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Their Possible Clinical Applications

International Journal of Molecular Sciences ◽

10.3390/ijms19103064 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3064 ◽

Cited By ~ 7

Author(s):

Hirofumi Okubo ◽

Akifumi Kushiyama ◽

Yusuke Nakatsu ◽

Takeshi Yamamotoya ◽

Yasuka Matsunaga ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Treatment Strategies ◽

Alcoholic Fatty Liver ◽

Glucagon Like Peptide 1 ◽

Global Increase ◽

Underlying Mechanisms ◽

Alcoholic Fatty Liver Disease

The rising prevalence of non-alcoholic fatty liver disease (NAFLD) parallels the global increase in the number of people diagnosed with obesity and metabolic syndrome. The gut-liver axis (GLA) plays an important role in the pathogenesis of NAFLD/non-alcoholic steatohepatitis (NASH). In this review, we discuss the clinical significance and underlying mechanisms of action of gut-derived secretory factors in NAFLD/NASH, focusing on recent human studies. Several studies have identified potential causal associations between gut-derived secretory factors and NAFLD/NASH, as well as the underlying mechanisms. The effects of gut-derived hormone-associated drugs, such as glucagon-like peptide-1 analog and recombinant variant of fibroblast growth factor 19, and other new treatment strategies for NAFLD/NASH have also been reported. A growing body of evidence highlights the role of GLA in the pathogenesis of NAFLD/NASH. Larger and longitudinal studies as well as translational research are expected to provide additional insights into the role of gut-derived secretory factors in the pathogenesis of NAFLD/NASH, possibly providing novel markers and therapeutic targets in patients with NAFLD/NASH.

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Pancreatic Adenocarcinoma: Improving Prevention and Survivorship

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_175222 ◽

2017 ◽

pp. 301-310

Author(s):

Davendra P. S. Sohal ◽

Field F. Willingham ◽

Massimo Falconi ◽

Kara L. Raphael ◽

Stefano Crippa

Keyword(s):

Pancreatic Cancer ◽

Breast And Ovarian Cancer ◽

Resectable Pancreatic Cancer ◽

Borderline Resectable ◽

Screening And Surveillance ◽

Hereditary Pancreatic Cancer ◽

Rising Incidence ◽

Peutz Jeghers Syndrome ◽

Systemic Therapies

Pancreatic cancer is a growing problem in oncology, given slowly rising incidence and continued suboptimal outcomes. A concerted effort to reverse this tide will require prevention, early diagnosis, and improved systemic therapy for curable disease. We focus on these aspects in detail in this study. Hereditary pancreatic cancer is an underappreciated area. With the growing use of genomics (both somatic and germline) in cancer care, there is increasing recognition of hereditary pancreatic cancer cases: around 10% of all pancreatic cancer may be related to familial syndromes, such as familial atypical multiple mole and melanoma (FAMMM) syndrome, hereditary breast and ovarian cancer, Lynch syndrome, and Peutz-Jeghers syndrome. Screening and surveillance guidelines by various expert groups are discussed. Management of resectable pancreatic cancer is evolving; the use of multiagent systemic therapies, in the adjuvant and neoadjuvant settings, is discussed. Current and emerging data, along with ongoing clinical trials addressing important questions in this area, are described. Surveillance recommendations based on latest ASCO guidelines are also discussed. Finally, the multimodality management of borderline resectable pancreatic cancer is discussed. The various clinicoanatomic definitions of this entity, followed by consensus definitions, are described. Then, we focus on current opinions and practices around neoadjuvant therapy, discussing chemotherapy and radiation aspects, and the role of surgical resection.

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The Evolving Role of Radiotherapy for Pediatric Cancers With Advancements in Molecular Tumor Characterization and Targeted Therapies

Frontiers in Oncology ◽

10.3389/fonc.2021.679701 ◽

2021 ◽

Vol 11 ◽

Author(s):

Colette J. Shen ◽

Stephanie A. Terezakis

Keyword(s):

Soft Tissue ◽

Molecular Diagnostics ◽

Targeted Therapies ◽

Soft Tissue Sarcomas ◽

Critical Element ◽

Precision Oncology ◽

Tumor Characterization ◽

Pediatric Cancers ◽

Systemic Therapies

Ongoing rapid advances in molecular diagnostics, precision imaging, and development of targeted therapies have resulted in a constantly evolving landscape for treatment of pediatric cancers. Radiotherapy remains a critical element of the therapeutic toolbox, and its role in the era of precision medicine continues to adapt and undergo re-evaluation. Here, we review emerging strategies for combining radiotherapy with novel targeted systemic therapies (for example, for pediatric gliomas or soft tissue sarcomas), modifying use or intensity of radiotherapy when appropriate via molecular diagnostics that allow better characterization and individualization of each patient’s treatments (for example, de-intensification of radiotherapy in WNT subgroup medulloblastoma), as well as exploring more effective targeted systemic therapies that may allow omission or delay of radiotherapy. Many of these strategies are still under investigation but highlight the importance of continued pre-clinical and clinical studies evaluating the role of radiotherapy in this era of precision oncology.

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The Contribution of Complement to the Pathogenesis of IgA Nephropathy: Are Complement-Targeted Therapies Moving from Rare Disorders to More Common Diseases?

Journal of Clinical Medicine ◽

10.3390/jcm10204715 ◽

2021 ◽

Vol 10 (20) ◽

pp. 4715

Author(s):

Felix Poppelaars ◽

Bernardo Faria ◽

Wilhelm Schwaeble ◽

Mohamed R. Daha

Keyword(s):

Iga Nephropathy ◽

Targeted Therapies ◽

Alternative Pathway ◽

Treatment Strategies ◽

Specific Treatment ◽

Lectin Pathway ◽

Phase 2 Trial ◽

Complement Inhibitors ◽

Common Diseases

Primary IgA nephropathy (IgAN) is a leading cause of chronic kidney disease and kidney failure for which there is no disease-specific treatment. However, this could change, since novel therapeutic approaches are currently being assessed in clinical trials, including complement-targeting therapies. An improved understanding of the role of the lectin and the alternative pathway of complement in the pathophysiology of IgAN has led to the development of these treatment strategies. Recently, in a phase 2 trial, treatment with a blocking antibody against mannose-binding protein-associated serine protease 2 (MASP-2, a crucial enzyme of the lectin pathway) was suggested to have a potential benefit for IgAN. Now in a phase 3 study, this MASP-2 inhibitor for the treatment of IgAN could mark the start of a new era of complement therapeutics where common diseases can be treated with these drugs. The clinical development of complement inhibitors requires a better understanding by physicians of the biology of complement, the pathogenic role of complement in IgAN, and complement-targeted therapies. The purpose of this review is to provide an overview of the role of complement in IgAN, including the recent discovery of new mechanisms of complement activation and opportunities for complement inhibitors as the treatment of IgAN.

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Preclinical Models in Prostate Cancer: Resistance to AR Targeting Therapies in Prostate Cancer

Cancers ◽

10.3390/cancers13040915 ◽

2021 ◽

Vol 13 (4) ◽

pp. 915

Author(s):

Wout Devlies ◽

Florian Handle ◽

Gaëtan Devos ◽

Steven Joniau ◽

Frank Claessens

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Targeted Therapies ◽

Treatment Strategies ◽

Resistance Mechanisms ◽

Cancer Therapies ◽

Cancer Resistance ◽

Tumor Resistance ◽

Preclinical Models

Prostate cancer is an androgen-driven tumor. Different prostate cancer therapies consequently focus on blocking the androgen receptor pathway. Clinical studies reported tumor resistance mechanisms by reactivating and bypassing the androgen pathway. Preclinical models allowed the identification, confirmation, and thorough study of these pathways. This review looks into the current and future role of preclinical models to understand resistance to androgen receptor-targeted therapies. Increasing knowledge on this resistance will greatly improve insights into tumor pathophysiology and future treatment strategies in prostate cancer.

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The Role of Inflammasomes in Atherosclerosis and Stroke Pathogenesis

Current Pharmaceutical Design ◽

10.2174/1381612826666200427084949 ◽

2020 ◽

Vol 26 (34) ◽

pp. 4234-4245

Author(s):

Deepaneeta Sarmah ◽

Aishika Datta ◽

Swapnil Raut ◽

Ankan Sarkar ◽

Birva Shah ◽

...

Keyword(s):

Atherosclerotic Plaque ◽

Treatment Strategies ◽

Cerebrovascular Diseases ◽

Cellular Injury ◽

Inflammatory Reactions ◽

Inflammatory Pathways

Inflammation is a devastating outcome of cerebrovascular diseases (CVD), namely stroke and atherosclerosis. Numerous studies over the decade have shown that inflammasomes play a role in mediating inflammatory reactions post cellular injury occurring after a stroke or a rupture of an atherosclerotic plaque. In view of this, targeting these inflammatory pathways using different pharmacological therapies may improve outcomes in patients with CVD. Here, we review the mechanisms by which inflammasomes drive the pathogenesis of stroke and atherosclerosis. Also, discussed here are the possible treatment strategies available for inhibiting inflammasomes or their up-stream/down-stream mediators.

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