Cancer treatment and research最新文献

The DNA damage response (DDR) protein MTH1 is sanitising the oxidized dNTP pool and preventing incorporation of oxidative damage into DNA and has an emerging role in mitosis. It is a stress-induced protein and often found to be overexpressed in cancer. Mitotic MTH1 inhibitors arrest cells in mitosis and result in incorporation of oxidative damage into DNA and selective killing of cancer cells. Here, I discuss the leading mitotic MTH1 inhibitor TH1579 (OXC-101, karonudib), now being evaluated in clinical trials, and describe its dual effect on mitosis and incorporation of oxidative DNA damage in cancer cells. I describe why MTH1 inhibitors that solely inhibits the enzyme activity fail to kill cancer cells and discuss if MTH1 is a valid target for cancer treatment. I discuss emerging roles of MTH1 in regulating tubulin polymerisation and mitosis and the necessity of developing the basic science insights along with translational efforts. I also give a perspective on how edgetic perturbation is making target validation difficult in the DDR field.

Considerable advances in the field of cancer have been made; however, these have not been translated into similar clinical progress which results in the high prevalence and increased cancer-related mortality rate worldwide. Available treatments have several challenges such as off-target side effects, non-specific long-term potential biodisruption, drug resistance, and overall inadequate response rates and high probability of recurrence. The limitations associated with independent cancer diagnosis and therapy can be minimized by an emerging interdisciplinary research field of nanotheranostics which include successful integration of diagnosis and therapy on a single agent using nanoparticles. This may offer a powerful tool in developing innovative strategies to enable "personalized medicine" for diagnosis and treatment of cancer. Nanoparticles have been proven to be powerful imaging tools or potent agents for cancer diagnosis, treatment, and prevention. The nanotheranostic provides minimally invasive in vivo visualization of drug biodistribution and accumulation at the target site with real-time monitoring of therapeutic outcome. This chapter intends to cover several important aspects and the advances in the field of nanoparticles-mediated cancer therapeutics including nanocarrier development, drug/gene delivery, intrinsically active nanoparticles, tumor microenvironment, and nanotoxicity. The chapter represents an overview of challenges associated with cancer treatment, rational for nanotechnology in cancer therapeutics, novel concepts of multifunctional nanomaterials for cancer therapy along with their classification and their clinical prospective in different cancers. A special focus is on the nanotechnology: regulatory perspective for drug development in cancer therapeutics. Obstacles hindering further development of nanomaterials-mediated cancer therapy are also discussed. In general, the objective of this chapter is to improve our perceptive in the design and development of nanotechnology for cancer therapeutics.

Malnutrition in cancer patients is highly prevalent. The metabolic and physiologic changes associated with the disease and the side effects of treatment regimens all combine together to produce a detrimental effect on the patient's nutritional status. A poor nutritional status significantly reduces the efficacy of treatment methods and the patient's overall chances of survival. Therefore, an individualized nutrition care plan is essential to counter malnutrition in cancer. Nutritional assessment is the first step of this process which sets the foundation for developing an effective intervention plan. Currently, there is no single standard method for nutritional assessment in cancer. Hence, to get a true picture of the patient's nutritional state, a comprehensive analysis of all aspects of the patient's nutritional status is the only reliable strategy. The assessment includes anthropometric measurements and evaluation of body protein status, body fat, inflammation markers, and immune markers. A thorough clinical examination which factors in the medical history and physical signs, along with the dietary intake patterns of the patient, is also important components of nutritional assessment of cancer patients. To facilitate with the process, various nutritional screening tools like patient-generated subjective global assessment (PGSGA), nutrition risk screening (NRS), and malnutrition screening tool (MST) have been developed. While these tools have their own benefits, they only give a glimpse of the nutritional problems and do not bypass the need for a complete assessment employing various methods. This chapter covers all four of the elements of nutritional assessment for cancer patients in detail.

Oncolytic virotherapy opens up avenues for cancer treatment by selectively targeting the cancer cells and destructs them either through direct lysis or by inducing an immune response in the tumor microenvironment. This platform technology utilizes a diverse range naturally existing or genetically modified oncolytic viruses for their immunotherapeutic potential. Due to the limitations associated with the conventional cancer therapies, immunotherapies using oncolytic viruses (OVs) have generated a great deal of interest in the modern era. Currently, several oncolytic viruses have entered clinical trials and have proven successful for a number of different cancers as monotherapies as well as in combination with the standard treatment methods like chemotherapy, radiotherapy, or immunotherapy. Efficacy of OVs can be further enhanced by utilizing several approaches. Efforts of the scientific community for getting better knowledge of individual patient tumor immune responses will enable medical community to treat cancer patients more precisely. In this regard, OV seems to be a part of multimodality cancer treatment option in the near future. In this chapter, the fundamental characteristics and mechanism of actions of oncolytic viruses are initially described and then overview of the important clinical trials of various oncolytic viruses for a number of cancers is presented.

As humanity continues to evolve, so do new treatments and the need to continually reevaluate and improve health care delivery. Cultural competency is at the core of improving health care delivery. However, cultural competency has proven to have limitations as it relates to the importance of on-going self-awareness, understanding, and consciousness of our own biases, culture, and values in the delivery of culturally sensitive patient and family-centric health care. The limited understanding of the true definition of cultural competency has hindered and blurred the guidelines on how to best communicate with patients and families throughout their care and end of life. With cultural humility, health care professionals can begin to lean into cultural confidence with resilience and curiosity.

The switch/sucrose non-fermenting (SWI/SNF) chromatin remodeling complex is a global regulator of gene expression known to maintain nucleosome-depleted regions at active enhancers and promoters. The mammalian SWI/SNF protein subunits are encoded by 29 genes and 11-15 subunits including an ATPase domain of either SMARCA4 (BRG1) or SMARCA2 (BRM) are assembled into a complex. Based on the distinct subunits, SWI/SNF are grouped into 3 major types (subfamilies): the canonical BRG1/BRM-associated factor (BAF/cBAF), polybromo-associated BAF (PBAF), and non-canonical BAF (GBAF/ncBAF). Pan-cancer genome sequencing studies have shown that nearly 25% of all cancers bear mutations in subunits of the SWI/SNF complex, many of which are loss of function (LOF) mutations, suggesting a tumor suppressor role. Inactivation of SWI/SNF complex subunits causes widespread epigenetic dysfunction, including increased dependence on antagonistic components such as polycomb repressor complexes (PRC1/2) and altered enhancer regulation, likely promoting an oncogenic state leading to cancer. Despite the prevalence of mutations, most SWI/SNF-mutant cancers lack targeted therapeutic strategies. Defining the dependencies created by LOF mutations in SWI/SNF subunits will identify better targets for these cancers.

The impact of nutritional patterns on the risk of breast cancer (BC) is well investigated in the oncology literature, including the type of diets and caloric intake. While obesity and elevated body mass index are well-reported critical risk factors of BC occurrence, there is an expanding area of oncology assessing the impact of caloric intake and nutritional patterns in patients with cancer. Caloric restriction and fast mimicking alimentary regimens have been consistently reported to improve survival outcomes based on preclinical models. Moreover, emerging clinical evidence has paved the way for new metabolic approaches for the treatment of BC, in addition to the established therapeutic arsenal or as alternative options. In this chapter, our aim is to discuss the principal strategies of metabolic manipulation through nutritional interventions for patients with BC as an innovative area of cancer therapy.

The hormonal therapy for cancer has become a household name and the series of experiments performed leading to the discovery of hormones use in the treatments of breast cancer. The hormones like antiestrogen, aromatase restrictors, antiandrogens, and use of extremely strong luteinizing hormone-releasing hormone agonists to perform a "medical hypophysectomy" because of their ability of causing desensitization in the pituitary gland have proven their value in the treatment of cancers over the last two decades. Millions of women still use hormonal therapy for menopause symptoms. Estrogen plus progestin or estrogen separately utilized as a menopause hormonal therapy throughout the world. Women receiving different premenopausal and postmenopausal hormonal therapies are on higher risk of having ovarian cancer. The risk of ovarian cancer did not increase with the increase of duration of hormonal therapy. Postmenopausal hormone use was found to be inversely related to major colorectal adenomas.

Targeted therapy and personalized medicine are novel emerging disciplines of cancer research intended for treatment and prevention. One of the most significant advancements in modern oncology is the shift from an organ-centric strategy to a personalized strategy guided by deep molecular analysis. This shift in view, which focuses on the tumour's precise molecular changes, has paved the way for individualized treatment. Researchers and clinicians are using targeted therapies to select the best treatment available based on the molecular characterization of malignant cancer. In the treatment of a cancer, personalized medicine entails the use of genetic, immunological, and proteomic profiling to provide therapeutic alternatives as well as prognostic information about cancer. In this book, targeted therapies and personalized medicine have been covered for specific malignancies, including latest FDA-approved targeted therapies and it also sheds light on effective anti-cancer regimens and drug resistance. This will help to enhance our ability to conduct individualized health planning, make early diagnoses, and choose optimal medications for each cancer patient with predictable side effects and outcomes in a quickly evolving era. Various applications and tools' capacity have been improved for early diagnosis of cancer and the growing number of clinical trials that choose specific molecular targets reflects this predicament. Nevertheless, there are several limitations that must need to be addressed. Hence, in this chapter, we will discuss recent advancements, challenges, and opportunities in personalized medicine for various cancers, with a specific emphasis on target therapies in diagnostics and therapeutics.

Cancer is a complex disease. According to the Globocan survey, 63% deaths are due to cancer. There are some conventional methods that are used to treat cancer. However, certain treatment modalities are under clinical trials still. The success of treatment depends on type and stage of cancer, locality, and patient's response to that specific treatment. Most widely used treatments are surgery, radiotherapy, and chemotherapy. Personalized treatment approach has some promising effects, yet some of the points are still unclear. This chapter has provided the overview of some of the therapeutic modalities; however, the therapeutic potential has been discussed in details throughout the book.