scholarly journals Targeting AVIL, a New Cytoskeleton Regulator in Glioblastoma

2021 ◽  
Vol 22 (24) ◽  
pp. 13635
Author(s):  
Robert Cornelison ◽  
Laine Marrah ◽  
Drew Horter ◽  
Sarah Lynch ◽  
Hui Li
Keyword(s):  
Radiation Therapy ◽  
Cytoreductive Surgery ◽  
Driving Force ◽  
Standard Of Care ◽  
Actin Binding ◽  
Targeted Chemotherapy ◽  
Novel Treatments ◽  
Dismal Prognosis ◽  
New Treatments ◽  
Fight Against Cancer

Glioblastoma (GBM) is the most common adult neural malignancy and the deadliest. The standard of care is optimal, safe, cytoreductive surgery followed by combined radiation therapy and alkylating chemotherapy with temozolomide. Recurrence is common and therapeutic options in the recurrent setting are limited. The dismal prognosis of GBM has led to novel treatments being a serious roadblock in the field, with most new treatments failing to show efficacy. Targeted therapies have shown some success in many cancers, but GBM remains one of the most difficult to treat, especially in recurrence. New chemotherapeutic directions need to be explored, possibly expanding the targeted chemotherapy spectrum in previously unforeseen ways. In this perspective paper, we will explain why AVIL, an actin-binding protein recently found to be overexpressed in GBM and a driving force for GBM, could prove versatile in the fight against cancer. By looking at AVIL and its potential to regulate FOXM1 and LIN28B, we will be able to highlight a way to improve outcomes for GBM patients who normally have very little hope.

scholarly journals Making Sense of Current and Emerging Therapies in Pancreatic Cancer: Balancing Benefit and Value

2015 ◽  
pp. e222-e227 ◽  
Author(s):  
Daniel H. Ahn ◽  
Andrew H. Ko ◽  
Neal J. Meropol ◽  
Tanios S. Bekaii-Saab
Keyword(s):  
Pancreatic Cancer ◽  
Standard Of Care ◽  
The United States ◽  
Economic Effects ◽  
Making Sense ◽  
Dismal Prognosis ◽  
Emerging Therapies ◽  
Metastatic Setting ◽  
Localized Disease ◽  
New Treatments

Pancreatic cancer remains the fourth leading cause of cancer deaths in the United States with a dismal prognosis and a 5-year survival of less than 5% across all stages.1In 2014, there were approximately 46,420 new cases of pancreatic cancer with only 9% of patients having localized disease.2Given that the vast majority of patients present with advanced disease, much of the focus for drug development has been in the metastatic setting, which is evident with the advent of two combination chemotherapy regimens for this indication. Although conventional cytotoxic chemotherapy remains the standard of care, an ongoing search for novel therapeutic approaches continues. We will highlight several new approaches here, with a particular emphasis on immunotherapeutic strategies. We will also introduce concepts regarding the potential economic effects associated with the development and implementation of new treatments in pancreatic cancer.

scholarly journals Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

2016 ◽  
Vol 34 (21) ◽  
pp. 2468-2477 ◽  
Author(s):  
Vijay Ramaswamy ◽  
Thomas Hielscher ◽  
Stephen C. Mack ◽  
Alvaro Lassaletta ◽  
Tong Lin ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Posterior Fossa ◽  
Cytoreductive Surgery ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Adjuvant Radiation ◽  
Molecular Subgroup ◽  
External Beam Irradiation ◽  
Dismal Prognosis

Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Methods Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

scholarly journals Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis from Colorectal Cancer

2020 ◽  
Vol 33 (06) ◽  
pp. 372-376
Author(s):  
Hideaki Yano
Keyword(s):  
Colorectal Cancer ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Peritoneal Metastasis ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Peritoneal Cancer Index ◽  
Systemic Disease ◽  
Good Reason ◽  
Standard Of Care ◽  
Peritoneal Cancer

AbstractPeritoneal metastasis from colorectal cancer (PM-CRC) is used to be considered a systemic and fatal condition; however, it has been growingly accepted that PM-CRC can still be local disease rather than systemic disease as analogous to liver or lung metastasis.Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now considered an optimal treatment for PM-CRC with accumulating evidence. There is a good reason that CRS + HIPEC, widely accepted as a standard of care for pseudomyxoma peritonei (PMP), could be a viable option for PM-CRC given a similarity between PM-CRC and PMP.Recent years have also seen that modern systemic chemotherapy with or without molecular targeted agents can be effective for PM-CRC. It is possible that neoadjuvant or adjuvant chemotherapy combined with CRS + HIPEC could further improve outcomes.Patient selection, utilizing modern images and increasingly laparoscopy, is crucial. Particularly, diagnostic laparoscopy is likely to play a significant role in predicting the likelihood of achieving complete cytoreduction and assessing the peritoneal cancer index score.

scholarly journals SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020)

2021 ◽  
Vol 23 (5) ◽  
pp. 980-987 ◽  
Author(s):  
E. Nadal ◽  
J. Bosch-Barrera ◽  
S. Cedrés ◽  
J. Coves ◽  
R. García-Campelo ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Early Stage ◽  
Asbestos Exposure ◽  
Standard Of Care ◽  
Tumor Board ◽  
Pleural Mesothelioma ◽  
Therapeutic Approaches ◽  
Dismal Prognosis ◽  
Line Chemotherapy ◽  
Multidisciplinary Tumor Board

AbstractMesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.

scholarly journals De-Escalation of Therapy for Patients with Early-Stage Squamous Cell Carcinoma of the Anus

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2099
Author(s):  
Eric Miller ◽  
Jose Bazan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Intensity Modulated Radiation Therapy ◽  
Late Toxicity ◽  
Standard Of Care ◽  
The Elderly ◽  
Current Standard

The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly in the elderly, with increased mortality in this age group. While the current standard of care for localized SCCA remains chemoradiation (CRT), completion of this treatment can be challenging with risks for severe acute and late toxicity. It remains unclear if full course CRT is required for the management of early-stage SCCA or if de-escalation of treatment is possible without compromising patient outcomes. Alternative therapies include radiation therapy alone or local excision for appropriate patients. Modifying standard CRT may also reduce toxicity including the routine use of intensity-modulated radiation therapy for treatment delivery, modification of treatment volumes, and selection and dosing of concurrent systemic therapy agents. Finally, we provide an overview of currently accruing prospective trials focused on defining the role of de-escalation of therapy in patients with early-stage SCCA.

Immunotherapy in Pancreatic Cancer

2020 ◽  
Vol 04 (04) ◽  
pp. 351-357
Author(s):  
Bassel F. El-Rayes ◽  
Mehmet Akce
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Standard Of Care ◽  
Ongoing Research ◽  
Modest Improvement ◽  
Major Barrier ◽  
Dismal Prognosis ◽  
Rigorous Research ◽  
Tumor Mutational Burden ◽  
Immunosuppressive Tumor Microenvironment

AbstractPancreatic cancer has a dismal prognosis and is projected to be the second most common cause of cancer-related mortality by 2030. Although modest improvement in survival with current conventional cytotoxic chemotherapy-based regimens, 5-year overall survival is still 9%. Despite becoming standard of care in several malignancies, single agent or dual check point inhibitor therapy is not effective in pancreatic cancer except in subgroup of patients with high microsatellite instability or high tumor mutational burden. Profoundly immunosuppressive tumor microenvironment of pancreatic cancer is a major barrier for success of immunotherapy. Rigorous research efforts are underway to explore immune-based combination therapy with chemotherapy, radiation therapy, stroma-modifying agents, vaccines, and targeted therapies. This article aims to provide a review of the ongoing research in pancreatic cancer immunotherapy.

scholarly journals Dosimetric comparison between 3D conformal and intensity-modulated radiation therapy for prostate cancer

2010 ◽  
Vol 9 (2) ◽  
pp. 77-85 ◽  
Author(s):  
Courtney Buckey ◽  
Gregory Swanson ◽  
Sotirios Stathakis ◽  
Nikos Papanikolaou
Keyword(s):  
Radiation Therapy ◽  
Organs At Risk ◽  
External Beam Radiotherapy ◽  
Radiation Therapy Oncology Group ◽  
Intensity Modulated Radiation Therapy ◽  
Standard Of Care ◽  
Target Volume ◽  
Conformal Radiation Therapy ◽  
Intensity Modulated ◽  
3D Crt

AbstractBackground and Purpose: Intensity-modulated radiation therapy (IMRT) is considered by many to be the standard of care in the delivery of external-beam radiotherapy treatments to the prostate. The purpose of this study is to assess the validity of the purported benefits of IMRT.Materials and Methods: Treatment plans were produced for 10 patients using both 3D conformal radiation therapy (3D-CRT) and IMRT, utilising the dose constraints recommended by the Radiation Therapy Oncology Group (RTOG) 0415 protocol. Three IMRT modalities used in this study were linear accelerator based IMRT, helical tomotherapy, and serial tomotherapy. The prescription to the target, 76 Gy, was the same for all plans.Results: In general the 3D-CRT plans satisfied the RTOG criteria for planning target volume (PTV) coverage, and met or bettered the dose criteria for the organs at risk. PTV coverage was more homogeneous for the IMRT plans than the 3D-CRT plans but not significantly improved.Conclusions: Technically, because the IMRT plans required greater effort for the optimisation, longer treatment times and higher monitor units, the use of IMRT for the fulfilment of the protocol’s dosimetric goals was not justified using these constraints.

Preclinical activity of cobimetinib alone or in combination with chemotherapy and targeted therapies in renal cell carcinoma

2021 ◽  
Author(s):  
Lichen Zhang ◽  
Deqiong Xie ◽  
Yonghua Lei ◽  
Aoli Na ◽  
Lei Zhu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Mapk Pathway ◽  
Standard Of Care ◽  
Underlying Mechanism ◽  
Mek Inhibitor ◽  
Tumor Formation ◽  
Pathway Inhibition ◽  
New Treatments

Background: The poor outcome of advanced renal cell carcinoma (RCC) necessitates new treatments. Cobimetinib is a MEK inhibitor and approved for the treatment of melanoma. This work investigated the efficacy of cobimetinib alone and in combination with anti-RCC drugs. Methods: Proliferation and apoptosis assays were performed, and combination index was analyzed on RCC cell lines (CaKi-2, 786-O, A-704, ACHN and A489) and xenograft models. Immunoblotting analysis was conducted to investigate the MAPK pathway. Results: Cobimetinib was active against RCC cells, with IC50 at 0.006–0.8μM, and acted synergistically with standard-of-care therapy. Cobimetinib at nontoxic doses prevented tumor formation, inhibited tumor growth and enhanced efficacy of 5-fluorouracil, sorafenib and sunitinib via suppressing Raf/MEK/ERK, leading to MAPK pathway inhibition. Conclusion: Our findings demonstrate the potent anti-RCC activity of cobimetinib and its synergism with RCC standard-of-care drugs, and confirm the underlying mechanism of the action of cobimetinib.

scholarly journals Current and Novel Alkylators in Multiple Myeloma

2021 ◽  
Author(s):  
Fredrik Schjesvold ◽  
Albert Oriol
Keyword(s):  
Multiple Myeloma ◽  
Personalized Medicine ◽  
Standard Of Care ◽  
Current Data ◽  
Targeted Treatment ◽  
Novel Treatments ◽  
Alkylating Drugs ◽  
And Personalized Medicine

A large number of novel treatments for myeloma have been developed and approved, however alkylating drugs continue to be part of standard regimens, additionally, novel alkylators are currently being developed. We performed a non-systematized literary search for relevant papers and communications at large conferences, as well as exploiting the authors knowledge of the field to review the history, current use and novel concepts around traditional alkylators cyclophosphamide, bendamustine and melphalan and current data on the newly developed pro-drug melflufen. Even in the era of targeted treatment and personalized medicine, alkylating drugs continue to be part of standard-of-care in myeloma, and new alkylators are coming to the market.

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