The role of myeloid-derived suppressor cells in hematologic malignancies
This article focuses on the immunosuppressive impact of myeloid-derived suppressor cells (MDSCs) and the potential clinical implications in hematological malignancies. Recent findings MDSCs play a critical role in the regulation of the immune response in cancer. They inhibit activation of adaptive immune response and as a result foster the growth of the malignancy. Recent studies have shown that MDSCs serve as prognostic biomarkers and as targets for cancer immunotherapy. Preclinical and clinical studies have identified new approaches to deplete MDSC populations and inhibit MDSC function with combination immunomodulator...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen Source Type: research

New targets and technologies for CAR-T cells
Purpose of review Immunotherapy with gene-engineered chimeric antigen receptor (CAR)-T cells has curative potential in advanced malignancies and undergoes a surging preclinical and clinical development. Here, we present a selection of new targets and technologies that illustrate the progress that is being made with the aspiration to make CAR-T cell therapy a universally applicable and effective treatment in cancer medicine. Recent findings There is a rich pipeline of new target antigens for CAR-T cells in hematology and oncology that are rated based on uniformity but also stability of expression on tumor cells under t...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen Source Type: research

Targeting defective DNA repair in prostate cancer
Purpose of review Prostate cancer is the second leading cause of cancer death in men. Characterization of the genomic landscape of prostate cancer has demonstrated frequent aberrations in DNA repair pathways, identifiable in up to 25% patients with metastatic disease, which may sensitize to novel therapies, including PARP inhibitors and immunotherapy. Here, we summarize the current clinical landscape and future horizons for targeting defective DNA repair pathways in PC. Recent findings Several clinical trials have demonstrated efficacy of different PARP inhibitors in metastatic castration-resistant prostate cancer (mC...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen Source Type: research

Antibody–drug conjugates in breast cancer: the chemotherapy of the future?
Purpose of review Antibody–drug conjugates (ADCs) represent an interesting new class of anticancer agents, capable of exploiting the specificity of monoclonal antibodies toward cellular-antigens for a targeted release of potent cytotoxic drugs, with a potential increased activity and reduced toxicity compared with traditional chemotherapies. The aim of this article is to review the efficacy and safety of ADCs in breast cancer. Recent findings Following the approval of T-DM1 both in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer, novel anti-HER2 ADCs have been investigated. ...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen Source Type: research

Targeting molecular subtypes in solid cancers: successes and failures
Purpose of review We herein review some of the major patterns of resistance and lessons learned from the use of earlier targeted therapies in two genotype-driven solid tumors. Recent findings Targeted agents have rapidly expanded in the field of oncology over the past 2 decades. The breakthroughs achieved by these agents have been, however, hindered by the inevitable development of drug resistance. Intrinsic or acquired mechanisms of resistance eventually lead to treatment tolerance and tumoral plasticity with phenotypic switch and evasion of the original targeted pathway. Failures in such therapies also result from p...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen Source Type: research

Advances in immunotherapy for cervical cancer
Purpose of review Novel therapies are needed for the treatment of recurrent cervical cancer. The best chemotherapy regimen to date has a response rate of 48% with an overall survival of 17 months, with limited options for second-line chemotherapy. Immunotherapy can induce a strong immune response in cervical cancer due to retained viral antigens and is reviewed in this article. Recent findings Current clinical trials include treatment with Listeria that elicits an immune response against the E7 oncoprotein and active vaccines against the E7 oncoprotein. Although the response rates to programmed cell death 1 (PD-1) inh...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: GYNECOLOGIC CANCER: Edited by Jean A. Klastersky Source Type: research

Progress in the management of endometrial cancer (subtypes, immunotherapy, alterations in PIK3CA pathway): data and perspectives
This article will cover the updated data in endometrial cancer molecular classification and its correlation with the outcomes in randomized clinical trials (e.g., PORTEC-3). Moreover, we will review the latest data regarding checkpoint blockade molecules (CPB) in the recurrent setting and how they are changing the treatment landscape. In addition, the role of the PI3K inhibitors, their activity, and toxicity profile will be described. Summary As result of the incorporation of molecular classification in our daily practice, the adjuvant treatment in endometrial cancer is rapidly evolving and leading to a new paradigm. Th...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: GYNECOLOGIC CANCER: Edited by Jean A. Klastersky Source Type: research

Immunotherapy in gynecological cancers: where are we?
We report here the results of the clinical trials and present the ongoing trial in this area. Recent findings Immunotherapy has become a pillar of cancer treatment improving the prognosis of many patients with a broad variety of solid malignancies. Unfortunately, until recently the progress achieved in some other tumors has not been seen in the majority of patients with gynecological cancer. Except for some subgroups of endometrial cancers the immune checkpoint inhibitors in monotherapy have shown unsatisfactory results. However, several combinations of immunotherapy with other drugs are under investigation and are very...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: GYNECOLOGIC CANCER: Edited by Jean A. Klastersky Source Type: research

HIPEC in advanced epithelial ovarian cancer: why is there controversy?
Purpose of review The randomized OVHIPEC study provided further evidence that adding heated intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery significantly improved recurrence-free and overall survival in stage III epithelial ovarian cancer (EOC) patients, who were ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. Because opinions have been divided as to whether HIPEC is now a new standard of care for advanced EOC, the pros and cons of this approach are examined. A comparison with the ongoing discussion about the role of intraperitoneal chemotherapy is made. Rece...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: GYNECOLOGIC CANCER: Edited by Jean A. Klastersky Source Type: research

Role of Poly (ADP-Ribose) Polymerase inhibitors beyond BReast CAncer Gene-mutated ovarian tumours: definition of homologous recombination deficiency?
Purpose of review PARP inhibitors have transformed the management of BRCA mutant (BRCAmut) high-grade serous and endometroid ovarian cancer (HGOC). However, it is clear that the benefit can be extended beyond this subgroup, particularly to those cancers with homologous recombination repair deficiency (HRD). We review emerging molecular and clinical data to support the use of PARP inhibitors in HRD HGOC and discuss the advantages and disadvantages of different HRD assays. Recent findings Several phase 3 trials support the use of PARP inhibitor maintenance therapy beyond those patients with BRCAmut in the first-line and...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: GYNECOLOGIC CANCER: Edited by Jean A. Klastersky Source Type: research

Chimeric antigen receptor T-cell lymphoma immunotherapy: the next questions
Purpose of review Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of adoptive cellular immunotherapy targeting CD19 in its most advanced form. Up to 30% of infused patients achieve long-term survival, meaning that 70% of patients still fail to respond or relapse after therapy. This review will address the unresolved issues relating to responders’ characterization, relapse prediction, and prevention, CAR T-cell construct optimization, rational combination with other therapies and treatment toxicity, focusing on the management of relapsed/refractory lymphoma patients. Recent findings Many new anti...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: LYMPHOMA: Edited by Dominique Bron and Christian Chabannon Source Type: research

Opportunities and challenges associated with the evaluation of chimeric antigen receptor T cells in real-life
Purpose of review With the approval of the first chimeric antigen receptor (CAR)-T cell products on the market, the European Medicines Agency (EMA) required market authorization holders (MAHs) to monitor the long-term efficacy and safety of CAR-T cells for 15 years after administration. In 2019, the cellular therapy module of the European Society for Blood and Marrow Transplantation (EBMT) registry received a positive qualification opinion from the EMA indicating that the registry fulfills the essential needs to capture such data. We investigated its broader implication. Recent findings Since 2020, the cellular therap...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: LYMPHOMA: Edited by Dominique Bron and Christian Chabannon Source Type: research

Clinical data, limitations and perspectives on chimeric antigen receptor T-cell therapy in multiple myeloma
Purpose of review Despite considerable therapeutic advances over the last decade, multiple myeloma remains an incurable disease. Novel treatment strategies are urgently needed. T cells can be genetically modified to express chimeric antigen receptors (CARs) targeting defined surface antigens on tumor cells. To date, over 90 clinical trials investigating the use of CAR T cells in multiple myeloma have been registered. Recent findings Although two CD19-directed CAR T-cell products have been approved, CD19 surface expression on plasma cells is limited or absent and CAR T-cell therapy in multiple myeloma is less advanced....
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: LYMPHOMA: Edited by Dominique Bron and Christian Chabannon Source Type: research

CD19-directed CAR T-cell therapy in B-cell NHL
Purpose of review CD19-directed chimeric antigen receptor (CAR) T-cell therapy is a valuable new treatment option for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. The aim of this review is to give an overview of the pivotal phase I/II trials, emerging real-world evidence and ongoing trials. Recent findings For decades, attempts at improvement of the poor prognosis of patients with R/R large B-cell lymphoma with new treatment regimens have been disappointing. Since the first report of CD19-directed CAR-T-cell therapy in 2010, three constructs have been tested in large phase I/II trials and resul...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: LYMPHOMA: Edited by Dominique Bron and Christian Chabannon Source Type: research

Overcoming key challenges in cancer immunotherapy with engineered T cells
Purpose of review A number of clinical trials are currently testing chimeric antigen receptor (CAR) and T cell receptor (TCR) engineered T cells for the treatment of haematologic malignancies and selected solid tumours, and CD19-CAR-T cells have produced impressive clinical responses in B-cell malignancies. Here, we summarize the current state of the field, highlighting the key aspects required for the optimal application of CAR and TCR-engineered T cells for cancer immunotherapy. Recent findings Toxicities, treatment failure and disease recurrence have been observed at different rates and kinetics. Several strategies...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: LYMPHOMA: Edited by Dominique Bron and Christian Chabannon Source Type: research