Magyar onkologia
-
Immunotherapy proved to be effective in various forms of cancer but it is in its infancy in colorectal cancer, although the Immunoscore was developed to classify this tumor immunologically. Various forms of immunotherapy were tested in early clinical trials but anti-PD-1 antibodies seem the most promising so far. These studies also revealed that one particular molecular subgroup of colorectal cancer, the microsatellite instable variant, is extremely sensitive for such modality.
-
Similarly to other malignancies, immune checkpoint inhibitor therapy is a revolutionary, effective new treatment possibility for lung cancer. In lung cancer carcinogenesis is related mainly to tobacco smoking with high somatic mutation rate and immunogenicity. The PD-1 inhibitor nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab is a labelled indication in second line setting in advanced nonsmall cell lung cancer (NSCLC). ⋯ In this selected patient population, progression-free survival has doubled, and overall survival was significantly better in pembrolizumab-treated patients compared to those receiving standard of care. Pembrolizumab treatment became a new first line standard of care in advanced NSCLC. There are numerous ongoing clinical trials in lung cancer with immune checkpoint inhibitors in combination with cytotoxic chemotherapy, targeted agents, or in adjuvant setting.
-
The past three decades of immunology research led to a drastic increase in the knowledge of antitumor immune response mechanisms and in parallel to a rapid development in various antitumor immune therapy strategies. This will most probably result in the implementation of immunotherapeutic protocols within the standard anticancer regimens in a very near future. Though, it is obvious that combination of immunotherapy with traditional anticancer treatment modalities will only be legitimate if the combination has at least an additive, or perhaps a synergistic effect. ⋯ It is also known by now that local irradiation due to its out-of-field effects has systemic immune modulatory capacity, too. In the light of all these novel findings the optimal combination between antitumor immunotherapy and radiotherapy has become an increasing option. The first part of the present review summarizes the main antitumor mechanisms that can be influenced by ionizing radiation, and the second part attempts to provide a comprehensive overview of those antitumor immunotherapeutic modalities that are currently being used in combination with radiotherapy in preclinical and/or clinical trials for the treatment of various tumors.
-
Review
[Unblocking antitumor immune response: novel possibilities for the immunotherapy of melanoma].
Recent advances in tumor immunology, a better understanding of mechanisms regulating the immune response has led to experimental and clinical testing of a novel type of immunotherapeutics: antibodies blocking negative regulatory mechanisms of T-cell activation [corrected]. The application of the CTLA-4 antagonist ipilimumab, the prototype of this new class of immune stimulating agents, represents the first treatment that resulted in significant prolongation of the survival of metastatic melanoma patients in randomized, controlled trial, leading to the approval of its use for the therapy of these patients in 2011. Together with the BRAF inhibitor vemurafenib, which was also approved in 2011, ipilimumab has changed the standard therapy of metastatic melanoma, and also paved the way for other agents aiming at influencing immune regulating molecules, of which antibodies blocking the PD-1 pathway also showed promising clinical activity. ⋯ The spectrum of side effects is different from that of conventional therapies, and a large part of them is caused by the enhanced systemic immune activity. In order to spare non-responding patients of the severe side effects and to increase response rate, the search for biomarkers that could help in identifying patients likely to react to the treatment represents an important focus of studies. Furthermore, development of combinations with other immunotherapeutic modalities, chemo- or targeted therapies may further increase the efficiency of immunomodulatory antibodies.
-
The last several years have seen extraordinary progress in the management of patients with castration resistant prostate cancer (CRPC). Although metastatic prostate cancer remains an incurable disease, substantial advances have been made in therapeutic options. Development of novel agents that modulate the androgen receptor pathway, growth factor signalling pathways, and immune function and bone targeting pathways has been the focus of therapeutic strategies because of its significance in the biology of prostate cancer progression. ⋯ Based on phase III clinical trials cabazitaxel, abiraterone acetate, sipuleucel-T and denosumab represent available therapeutic options in this setting, radium-223 chloride and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab) or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan), while other emerging molecules have shown hopeful results. The aim of this review is to summarize the most important new findings for metastatic CRPC (mCRPC) according to the different molecular pathways and to discuss their potential influence on future management of this disease.