Release date: 2017-04-07
On March 24th, a team of scientists from Novartis Institutes for BioMedical Research published a review article entitled "Prospects for targeted and conventional cancer therapy with immunotherapy" in Nature Reviews Cancer.
According to the abstract, cancer treatment research has focused on two different directions over the past 25 years. On the one hand, scientists are committed to understanding the genetic factors that lead to tumorigenesis. These results have driven the development of targeted drugs. On the other hand, researchers are also exploring the mechanisms behind tumors that escape the body's immune system attacks. These advances have driven the development of tumor immunotherapy. The most successful immunotherapy currently is an immunological checkpoint inhibitor. These drugs produce a sustained clinical response in many different types of cancer patients.
Integrating these different types of therapies now opens up new opportunities for improving cancer treatment. The authors believe that understanding the role of targeted therapies, as well as traditional chemotherapy and radiotherapy in inducing anti-tumor immunity, will help drive the design of combination therapy strategies.
This review examines recent advances in "how targeted therapy affects molecular pathways that control immune cell function and anti-tumor immunity"; it also targets low-molecular-weight targeting of key immune regulatory pathways (low-molecular-weight) Inhibitors, chemotherapy and radiotherapy were discussed. The article states that all of these therapies may become part of an effective combination therapy.
The main body of the review is divided into five parts. The following is a compilation of some of the contents:
1# Stimulation of innate immunity
Image source: Nature Reviews Cancer
The innate immune system of cells has antigen presentation, T cell co-stimulation and direct tumor cell killing function, which is crucial for the initiation, maintenance and programming of tumor immune responses. In this section, the authors discuss treatments that stimulate innate immune responses, such as amplifying antigen presentation.
2# TCM function regulation (Modulation of T cell function)
Image source: Nature Reviews Cancer
In this section, the authors say that the growth factor receptor and TCR signals share the same molecular pathway (Figure 2). Therefore, targeted therapy may also modulate the function of T cells and other immune cells, and combined with immunotherapy to prolong clinical response. This section focuses on MEK inhibitors, PI3K–AKT–mTOR pathway inhibitors, IAP inhibitors, etc. (Table 1).
Form source: Nature Reviews Cancer
3 # regulating tumor microenvironment (Modulation of the TME)
Image source: Nature Reviews Cancer
The development of tumors also causes changes in surrounding tissues, leading to a complex tumor microenvironment composed of immune cells, endothelial cells, mesenchymal cells, extracellular matrices and metabolites. The synergistic interaction between cancer cells and the matrix leads to the growth and deterioration of cancer, and is a major obstacle to anti-tumor immunity. Therefore, therapies designed to modulate the tumor microenvironment (such as regulating metabolites, growth factors, and cytokines) are expected to create an environment that supports anti-tumor immune responses (Figure 3).
4 # chemotherapy and radiation therapy (Chemotherapy and radiation therapy)
In the past decade, preclinical and clinical data have shown that some traditional chemotherapy may work in part through immunostimulatory mechanisms such as anthracyclines. This section first introduces some important research advances in recent years (see the figure below for related papers), including the results of a combination of chemotherapy and popular immunological checkpoint inhibitors.
In addition to chemotherapy, recent data suggest that radiotherapy can also lead to multiple immune stimulatory functions, including tumor-associated antigens and the release of damage-associated molecular patterns. These functions support the initiation of immune cells and help fight tumor immunosuppression. This review focuses on the latest advances in radiotherapy combined with CTLA-4 antibodies.
Xiao Bian noted that in June last year, Cell's Trends in Cancer magazine published a viewpoint article entitled "Radiotherapy: Changing the Game in Immunotherapy", discussing the combination therapy of radiotherapy and immunotherapy. The specific content of Xiaobian was introduced in " Cell: radiotherapy, or will change the "cancer immunotherapy " article.
Challenge # 5 combination therapy (Challenges for combination therapies)
In the final part of the article, the authors summarized three major challenges in developing a combination therapy strategy: 1) a deeper understanding of the impact of targeted, traditional, and immunotherapy on the patient's immune system; 2) need to be identified Proper dose and sequence optimize the effectiveness, toxicity, and tolerability of combination therapies; 3) Require a powerful approach to Prioritizing and Resourcing for the myriad possibilities of combination therapy.
They believe that the first major challenge, in part, can be addressed by in-depth study of clinical samples obtained from patients before and during treatment. These data from patient sample studies will facilitate the discovery of targets and the construction of more accurate preclinical models; it will also help identify appropriate combination therapies. In addition, data on toxicity, tolerability, and efficacy produced by small trials are also required for further clinical development of combination therapies.
Source: Bio-Exploration
Tetanus Shot,Tetanus Vaccine,Hepatitis B Injection,Hep B Vaccine
FOSHAN PHARMA CO., LTD. , https://www.foshanmedicine.com