EGFR-mutant NSCLC: emerging novel drugs
Purpose of review Despite the significant advances in EGFR-mutant nonsmall cell lung cancer (NSCLC), some challenges remain. One of the permanent and inevitable issues is the emergence of acquired resistance. Therefore, blocking the activation of EGFR pathway and overcoming drug resistance with novel agents are still in high demand. Here, we review the development of novel drugs in EGFR-mutant, advanced NSCLC, including targeting EGFR exon 20 insertion (EGFR20ins), and novel role of epidermal growth factor receptor, tyrosine kinase inhibitor (EGFR-TKIs) in early-stage NSCLC. Recent findings EGFR-TKIs as adjuvant...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker and Caicun Zhou Source Type: research

Malignant pleural mesothelioma: recent developments
Purpose of review Malignant pleural mesothelioma (MPM) is a rare, but aggressive tumor with still poor prognosis. In this article, we focus on recent developments in the management of MPM including diagnosis, staging, biomarkers, and treatment strategies. Recent findings Molecular markers such as programmed death-ligand 1 (PDL-1), Breast Cancer gene 1-associated protein gene, and cyclin-dependent kinase inhibitor 2A (CDKN2A) have prognostic impact and should be considered for assessment in patient samples. In addition to histological subtype and tumor pattern, tumor volumetry plays an increasing important role i...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker and Caicun Zhou Source Type: research

Immunotherapy combinations in advanced nonsmall cell lung cancer
Purpose of review The purpose of the review is to summarize immunotherapy combinations in advanced nonsmall cell lung cancer (NSCLC). Recent findings First-line platinum-based chemotherapy plus an immune checkpoint inhibitor has improved progression-free and overall survival compared to chemotherapy alone in patients with advanced NSCLC. Although the benefits appear to increase with higher programmed death ligand 1 (PD-L1) expression, patients with low PD-L1 also benefit. Nivolumab plus ipilimumab has also been established as a treatment option. Combinations of immune checkpoint inhibitors with olaparib or lenva...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker and Caicun Zhou Source Type: research

Immune checkpoint inhibitors in driver mutation-positive nonsmall cell lung cancer: is there a role?
This article aimed to comprehensively review the currently available data on the efficacy and safety of immune checkpoint blockade (ICB) for patients with driver mutation-positive lung cancer. Recent findings Despite the positive interaction between activation of oncogenic pathways and upregulated PD-L1 expression demonstrated in preclinical studies, the efficacy of single-agent ICB in patients with oncogenic mutation has largely been discouraging, except for those with KRAS mutations. The combination therapies using ICB with tyrosine kinase inhibitors (TKIs) for EGFR/ALK alteration raised a concern for the high inc...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker and Caicun Zhou Source Type: research

Neoadjuvant immunotherapy in nonsmall cell lung cancer
Purpose of review Immune-checkpoint inhibitors have improved treatment outcomes for metastatic nonsmall cell lung cancer (NSCLC). Whether this therapeutic potential might also translate into survival gains in earlier stages is an area of active research. Based on preclinical rationale the neoadjuvant administration of immunotherapeutic agents is of special interest. This review is intended to summarize the existing background, published early clinical evidence, and provide perspective on future developments regarding neoadjuvant immunotherapy in NSCLC. Recent findings Preclinical data and early clinical trials s...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker and Caicun Zhou Source Type: research

Tyrosine kinase inhibitors as induction therapy in nonsmall-cell lung cancer
Purpose of review TKI therapy has shown excellent efficacy and favorable tolerability in patients with mutation-positive nonsmall cell lung cancer. However, there is no clear consensus on the role of TKI as induction therapy. In this article, we reviewed recently published studies to analyze the benefits of tyrosine kinase inhibitors, in particular, EGFR TKIs and ALK TKIs, as inducible treatments for NSCLC. Recent findings Several clinical trials have recently presented their latest data, giving analysis of patient's survival benefits and adverse events. Initial results have demonstrated promising efficacy and s...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker and Caicun Zhou Source Type: research

Adjuvant therapy of operable nonsmall cell lung cancer: an update
Purpose of review The current status of postoperative adjuvant therapy for nonsmall cell lung cancer (NSCLC) is reviewed. Recent findings Cisplatin-based postoperative chemotherapy is a current standard of care for patients with stage II–III NSCLC who underwent complete resection. However, its benefit is limited. In these 20 years, the introduction of targeted therapies and immune checkpoint inhibitors has dramatically changed the treatment of metastatic lung cancer. The accumulated knowledge is now being applied in the adjuvant setting and many clinical trials are underway. Recently, postoperative osimert...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker and Caicun Zhou Source Type: research

Lung cancer in China: current and prospect
Purpose of review To describe the current status of lung cancer in China, including incidence, prevention, molecular testing and treatment. Recent findings Lung cancer presents a major public health issue and an enormous burden on society in China, because of its increasing incidence and high mortality. Several distinct gene profiles were associated with lung cancer in China: high EGFR mutation rate, low KRAS mutation rate and more comorbidity of HBV infection. Thus, local Chinese Society of Clinical Oncology Guidelines with more consideration of drug accessibility, regional development differences were highly r...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker and Caicun Zhou Source Type: research

131I-metaiodobenzylguanidine and peptide receptor radionuclide therapy in pheochromocytoma and paraganglioma
Purpose of review Pheochromocytomas and paragangliomas are rare tumors arising, respectively, from the adrenal medulla and extra-adrenal sympathetic or parasympathetic paraganglia. The main therapeutic objectives in case of metastatic disease are the reduction of tumor burden and the control of symptoms resulting from excessive catecholamine secretion. Treatment choices constitute not only a wait and see attitude, locoregional approaches, chemotherapy regiments but also radiopharmaceutical agents, and they should be discussed in a specialized multidisciplinary board. This review will briefly discuss the radiopharmaceut...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: ENDOCRINE TUMORS: Edited by Christiane Jungels Source Type: research

An update on adult forms of hereditary pheochromocytomas and paragangliomas
Purpose of review Pheochromocytomas and paragangliomas (PPGL) display a strong genetic determinism with 40% of inherited forms. The purpose of this review is to provide an update on current knowledge on adult forms of hereditary PPGL and their management. Recent findings PPGL are genetically-driven in 70% of cases, with germline and/or somatic mutations identified in more than 20 genes. Although eight new susceptibility genes have recently emerged, mutations on SDHx genes remain the most frequent. In addition to SDHB, mutations in SLC25A11, FH and MDH2 may predispose to a metastatic disease and somatic alteratio...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: ENDOCRINE TUMORS: Edited by Christiane Jungels Source Type: research

Adrenocortical carcinoma: current treatment options
Purpose of review In this article, we focus on the current and future treatment options for adrenocortical carcinoma (ACC). Recent findings Radical surgery remains the only curative treatment for ACC. Recent reports showed a longer overall survival (OS) in patients with high risk of recurrence treated with adjuvant mitotane; the time in target range (14–20 mg/l) is related to low risk of relapse both in adjuvant and in palliative setting. In patients who experience disease progression after etoposide, doxorubicin, cisplatin with mitotane (EDP-M), gemcitabine and metronomic capecitabine, or the less used ...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: ENDOCRINE TUMORS: Edited by Christiane Jungels Source Type: research

Epigenetic in medullary thyroid cancer: the role of microRNA in tumorigenesis and prognosis
Purpose of review MicroRNAs emerged as pivotal regulators of cell differentiation, growth, and cell death, suggesting their implication in tumorigenesis and prognosis of cancer. In the last decades, knowledge about the alterations of microRNAs in medullary thyroid cancer (MTC) is increasing. In this review, we try to summarize the most relevant findings regarding microRNA dysregulation in MTC. Recent findings A literature analysis was performed in MEDLINE for studies published up to August 2020. Comprehensively, at least 27 different microRNAs have been investigated in MTC showing evidence for overexpression or ...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: ENDOCRINE TUMORS: Edited by Christiane Jungels Source Type: research

Multikinase inhibitors for the treatment of radioiodine refractory thyroid cancer: what have we learned from the ‘real-world’ experience?
Purpose of review Several molecularly targeted drugs for treating radioiodine resistant differentiated thyroid carcinomas (RAIR-DTC) have been identified. Among these, sorafenib and lenvatinib have been approved for clinical use in many countries. The present review will analyze efficacy and safety ‘real-world’ data (RWD) emerging after their commercialization. Recent findings RWDs confirmed sorafenib and lenvatinib efficacy in terms of progression-free survival and, perhaps, overall survival improvement in patients with RAIR-DTC. Lenvatinib performance in RWDs appeared somehow lower than in randomiz...
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: ENDOCRINE TUMORS: Edited by Christiane Jungels Source Type: research

Editorial: Endocrine tumors, rare tumors
No abstract available (Source: Current Opinion in Oncology)
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: ENDOCRINE TUMORS: Edited by Christiane Jungels Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Oncology)
Source: Current Opinion in Oncology - December 5, 2020 Category: Cancer & Oncology Tags: EDITORIAL INTRODUCTIONS Source Type: research

Immunotherapy in multiple myeloma: when, where, and for who?
Purpose of review Immunotherapy is transforming treatment of multiple myeloma patients in all stages of their disease. This review will discuss recent developments in immunotherapy in multiple myeloma with a focus on antibodies, antibody–drug conjugates, and T-cell-redirection strategies. Recent findings CD38-targeting antibodies have single agent activity in multiple myeloma, and especially when combined with other drugs, are improving the clinical outcome of patients with newly diagnosed or relapsed/refractory multiple myeloma. Also the SLAMF7-targeting antibody, elotuzumab, improves the survival of relapsed/r...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: HEMATOLOGIC MALIGNANCIES: Edited by Miguel A. Sanz Source Type: research

Practical approach to the management of smoldering myeloma
Purpose of review The aim of this article is to review the diagnosis and risk stratification of smoldering myeloma (SMM), describe recently published data regarding the early treatment of SMM, and to provide practical strategies on how to manage patients with SMM in the clinic. Recent findings Recently published data from the ECOG E3A06 and GEM-CESAR studies supporting early intervention for certain subsets of high-risk SMM patients will be presented, and the relevance of these findings in relation to real-life application will be explored. Summary Accurate risk-stratification and standard of care for SMM is evolvi...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: HEMATOLOGIC MALIGNANCIES: Edited by Miguel A. Sanz Source Type: research

A precision medicine approach to management of acute myeloid leukemia in older adults
Purpose of review Therapy selection in older adults with acute myeloid leukemia (AML) can be challenging because of a higher incidence of high-risk cytogenetic and molecular features conferring chemoresistance and poor functional status leading to increased treatment-related toxicities. The purpose of this review is to highlight the recent advances in precision medicine in AML that have shown promise to improve outcomes of older adults. Recent findings The utilization of next generation sequencing to identify and target actionable mutations can influence therapy selection in one-third of patients and can result in hig...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: HEMATOLOGIC MALIGNANCIES: Edited by Miguel A. Sanz Source Type: research

Physical approaches to treat glioblastoma
Purpose of review Glioblastoma (GBM) patients have a poor prognosis despite the use of modern synergistic multimodal treatment strategies, with a progression-free survival estimated at 7–8 months, a median survival of 14–16 months and 5-year overall survival of 9.8%. Recent findings Physical methods hold the promise to act synergistically with classical treatments to improve the outcome of GBM patients. Fluorescent guided surgery with 5-aminolevulinic acid and tumor-treating fields therapy have already shown positive results in randomized phase III trials and have been incorporated in the standard manageme...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BRAIN AND NERVOUS SYSTEM: Edited by Marc Sanson Source Type: research

Mechanisms of invasion in glioblastoma
Purpose of review This review provides an overview of recent updates in understanding the mechanisms by which glioblastoma cells interact with their cellular and molecular partners within the microenvironment. Recent findings We have now a better knowledge of the cell populations involved in Glioblastoma (GBM) invasion. Recent works discovered the role of new molecular players in GBM invasion, and, most importantly, better models are emerging which better recapitulate GBM invasion. Summary Invasive properties of glioblastoma make complete surgical resection impossible and highly invasive cells are responsible for t...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BRAIN AND NERVOUS SYSTEM: Edited by Marc Sanson Source Type: research

Embryonal tumors of the central nervous system
Purpose of review This review aims to give an update on histopathological, molecular and clinical features of central nervous system (CNS) ‘embryonal’ tumors. Recent findings The taxonomy of previously called ‘CNS primitive neuroectodermal tumor’ (CNS PNET) has been deeply modified since the discovery of specific molecular profiles for each various sub-entity of these rare, mainly pediatric, tumors. The term ‘embryonal tumors’ now refers to medulloblastomas, atypical teratoid rhabdoid tumors (AT/RT) and other rare entities, defined by their specific histopathological features togeth...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BRAIN AND NERVOUS SYSTEM: Edited by Marc Sanson Source Type: research

Molecular alterations in meningioma: prognostic and therapeutic perspectives
Purpose of review To discuss recent advances in the meningioma biology and their clinical implications. Recent findings Meningioma is the most common primary intracranial tumor. Mostly benign, 20% of cases display an aggressive behavior despite best standard of care. The genetic landscape of meningiomas is divided according to NF2 mutational status. Although about 60% of meningiomas display NF2 mutations, the other share is more heterogenous. Mutations in TRAF7, SMO, v-akt murine thymoma viral oncogene homolog 1 (AKT1), PI3KCA and KLF4 are seen mostly in WHO grade 1 meningiomas. In higher grade meningiomas, mutations ...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BRAIN AND NERVOUS SYSTEM: Edited by Marc Sanson Source Type: research

Neurological complications of chimeric antigen receptor T cells and immune-checkpoint inhibitors: ongoing challenges in daily practice
Purpose of review The aim of this review is to summarize the most recent advances in the management of neurological toxicities associated with immune-checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR)-T cells. Recent findings The advent of cancer immunotherapies has dramatically improved the prognosis of several refractory and advanced neoplasms. Owing to their mechanism of action, cancer immunotherapies have been associated with a variety of immune-related adverse events (irAE). Neurological irAE are uncommon compared with other irAE, but they are associated with significant morbidity and mortality. Des...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BRAIN AND NERVOUS SYSTEM: Edited by Marc Sanson Source Type: research

Adjuvant treatment of early male breast cancer
Purpose of review Male breast cancer (MaBC) is a rare disease, and some challenges exist in its management because current treatment recommendations are extrapolated from trials that mostly excluded men. This review will revise all available data that could improve the treatment of MaBC, with a special focus on adjuvant systemic treatments. Recent findings To date, men with hormone receptor-positive breast cancer, who are candidates for adjuvant endocrine therapy, should be offered tamoxifen (TAM) for five years. Additional five years are possible, according to tolerance and recurrence risk. If TAM is contraindicated,...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BREAST CANCER: Edited by Giuseppe Curigliano Source Type: research

Combining poly(ADP-ribose) polymerase inhibitors and immune checkpoint inhibitors in breast cancer: rationale and preliminary clinical results
Purpose of review Recently, both immune checkpoint inhibitors and poly(ADP-ribose) polymerase inhibitors have demonstrated clinical benefit in some subsets of HER2-negative breast cancer patients. A biological rationale exists supporting a potential synergism between these compounds, which may further increase their antitumor activity in the clinic. Recent findings PARP inhibitors were shown to activate type I interferon pathway, thus eliciting local and general immune response, while inducing programmed cell death-ligand 1 (PD-L1) up-regulation. In addition, the DNA damages created by PARP inhibition may increase tum...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BREAST CANCER: Edited by Giuseppe Curigliano Source Type: research

Integrating immunotherapy in the (neo)adjuvant setting of early breast cancer
Purpose of review Breast cancer is a relative latecomer in the success story of immuno-oncology. In this review, we focus on the preclinical and clinical lines of evidence to justify the evaluation of immune checkpoint inhibition (ICI) for the curative-intent treatment of breast cancer, the latest and ongoing trials of (neo)adjuvant immunotherapy, and practical considerations in clinical practice associated with this new treatment paradigm. Recent findings Insights from the immunobiology of breast cancer have paved the way for the new frontier of immunotherapy in this malignancy, starting from advanced stages and movi...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BREAST CANCER: Edited by Giuseppe Curigliano Source Type: research

Can we cure oligometastatic disease? A practical point of view
Purpose of review To critically analyze the available evidence on oligometastatic breast cancer and to suggest therapeutic approaches for optimal management of these patients. Recent findings Unlike metastatic breast cancer, which remains incurable, patients with a limited number and extent of metastatic lesions, that is, oligometastatic disease, might achieve disease control and long-term survival when radical therapy of the primary tumor, if present, and metastatic disease is added to standard systemic therapy. However, the lack of a clear definition, variety of presentations, and the absence of biomarkers makes oli...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BREAST CANCER: Edited by Giuseppe Curigliano Source Type: research

How to treat lobular cancer in the adjuvant setting?
Purpose of review The aim of this review is to understand the clinical decision- making process for the management of patients with early invasive lobular breast cancer (ILC), thereby orienting clinicians across large areas of uncertainties and extrapolations. Recent findings The analysis of the principal evidence on the management of ILC, assessing the role and benefit of systemic treatments in the curative setting, have shed the light on the opportunity to escalate and de-escalate systemic therapies for ILC patients, based on the risk of recurrence and the intrinsic value of the treatments. To refine the selection o...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BREAST CANCER: Edited by Giuseppe Curigliano Source Type: research

Prevention of brain metastases in human epidermal growth factor receptor 2-positive breast cancer
Purpose of review For patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, treatments that could prevent or delay occurrence of brain metastases would improve outcome. Recent findings Few studies were specifically designed to assess brain metastasis prevention. Most evidence derives from subgroup analyses of randomized trials. In the first-line metastatic setting, lapatinib, was not superior to trastuzumab to prevent CNS metastases as first site of relapse. Pertuzumab when added to trastuzumab and taxane significantly delay occurrence of brain metastases. In the second line setting, tr...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BREAST CANCER: Edited by Giuseppe Curigliano Source Type: research

Targeting HER2 heterogeneity in early-stage breast cancer
Purpose of review HER2-positive (HER2+) breast cancer is clinically and biologically a heterogenous disease and not all patients benefit to the same extent from current anti-HER2 therapies. Recent findings Among HER2+ breast cancer, molecular intrinsic subtypes, PIK3CA mutation status, levels of HER2 gene/protein, immune infiltration, or intratumor heterogeneity modulate HER2-treatment sensitivity. HER2-enriched carcinomas, with high levels of HER2 and tumor-infiltrating lymphocytes (TILs) are highly sensitive to anti-HER2 therapies, regardless of chemotherapy. Luminal A/B tumors are more estrogen receptor-dependent t...
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: BREAST CANCER: Edited by Giuseppe Curigliano Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Oncology)
Source: Current Opinion in Oncology - October 17, 2020 Category: Cancer & Oncology Tags: EDITORIAL INTRODUCTIONS Source Type: research

Targeting microRNA in hematologic malignancies
Purpose of review MiRNAs are critical regulators for gene expression. Numerous studies have revealed how miRNAs contribute to the pathogenesis of hematologic malignancies. Recent findings The identification of novel miRNA regulatory factors and pathways crucial for miRNA dysregulation has been linked to hematologic malignancies. miRNA expression profiling has shown their potential to predict outcomes and treatment responses. Recently, targeting miRNA biogenesis or pathways has become a promising therapeutic strategy with recent miRNA-therapeutics being developed. Summary We provide a comprehensive overview of the r...
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

Fundamentals of liquid biopsies in metastatic prostate cancer: from characterization to stratification
Purpose of review In this review, we provide an overview of the recent developments and prospects on the applications of blood-based liquid biopsies, including circulating tumor DNA and circulating tumor cells, in metastatic prostate cancer. Recent findings Guidelines and consensus statements have been formulated to standardize preanalytical conditions that affect liquid biopsy analysis. Currently, there are four FDA approved assays for the analysis of liquid biopsies and many quantitative and qualitative assays are being developed. Comprehensive analyses of cell-free tumor DNA (ctDNA) and circulating tumor cells (CTC...
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

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 investigat...
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 ...
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

Indications of next-generation sequencing in non-Hodgkin's lymphoma
In this study, we will give an overview on the current and foreseeable indications of next-generation sequencing (NGS)-based technologies for the diagnosis, prognostic assessment and decision of individualized treatment strategy in lymphomas. Recent findings Recent NGS-based studies have offered a comprehensive knowledge of the genetic landscapes featuring B-cell and T-cell lymphomas, with identification of genomic biomarkers useful for a better subclassification and, therefore, for a more accurate diagnosis. NGS analyses in lymphoma have also unveiled recurrent somatic mutations representing novel potential therapeutic...
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: LYMPHOMA: Edited by Dominique Bron and Christian Chabannon Source Type: research

Editorial introductions
No abstract available (Source: Current Opinion in Oncology)
Source: Current Opinion in Oncology - August 18, 2020 Category: Cancer & Oncology Tags: EDITORIAL INTRODUCTIONS Source Type: research