Cancer treatment and research最新文献

Cancer and cardiovascular disease are the two major causes of morbidity and mortality in worldwide. Discovering new therapeutic agents for the management of breast cancer (BC) has increased the numbers of cancer survivors but with the risk of cardiovascular adverse events (CV-AEs). All drugs can potentially damage the cardiovascular system, with different types of clinical manifestations from ischemic myocardial disease to vasculitis, thrombosis or pericarditis. An early detection of CV-AEs guarantees an earlier treatment, which is associated with better outcomes. Cardio-oncology field enlarged its studies to improve prevention, monitoring and treatment of all cardiotoxic manifestations related to old or modern oncological agents. A multidisciplinary approach with a close partnership between oncologists and cardiologists is essential for an optimal management and therapeutic decision-making. The aim of this chapter is to review all types of cardiotoxic manifestations related to novel and old agents approved for treatment of BC patients including chemotherapy, anti-HER2 agents, cyclin-dependent kinase 4/6 inhibitors, PolyADP-ribose polymerase (PARP) inhibitors, antiangiogenic drugs and immunotherapy. We also focused our discussion on prevention, monitoring, treatment, and management of CV-AEs.

Identification of tumours that have homologous recombination deficiency (HRD) has become of increasing interest following the licensing of PARP inhibitors. Potential methods to assess HRD status include; clinical selection for platinum sensitive disease, mutational/methylation status, genomic scars/signature and functional RAD51 assays. Homologous recombination (HR) is a dynamic process with the potential to evolve over a disease course, particularly in relation to previous treatment. This is one of the major drawbacks of genomic scars/signatures, as they only demonstrate historic HR status. Functional HR assays have the benefit of giving a real time HR status readout and therefore have the potential for clearer identification of patients who may benefit from PARP inhibitors at that specific time point. However, the development of RAD51 foci assays ready for clinical practice has been challenging. Pre-clinical considerations have included; controlling for variation in tumour proliferation, tissue type and whether DNA damage induction is required. Furthermore, the assays require correlation with clinical outcomes, an understanding of how they complement current testing modalities and validation of test performance in large cohorts. Despite these challenges, given the profound benefit from PARP inhibitors seen in those with an HRD phenotype to date, the ongoing development and validation of these functional HR assays remains of high clinical importance.

Polymerase theta (POLθ) is the critical multi-domain enzyme in microhomology-mediated end-joining DNA double-stranded break repair. POLθ is expressed at low levels in normal tissue but is often overexpressed in cancers, especially in DNA repair deficient cancers, such as homologous-recombination cancers, rendering them exquisitely sensitive to POLθ inhibition secondary to synthetic lethality. Development of POLθ inhibitors is an active area of investigation with inhibitors of the N-terminal helicase domain or the C-terminal polymerase domain currently in clinical trial. Here, we review POLθ-mediated microhomology-mediated end-joining, the development of POLθ inhibitors, and the potential clinical uses of POLθ inhibitors.

There is no denying that many revolutions took place in the fight against cancer during the last decades. However, cancers have always managed to find new ways to challenge humankinds. Variable genomic epidemiology, socio-economic differences and limitations of widespread screening are the major concerns in cancer diagnosis and early treatment. A multidisciplinary approach is essentially to manage a cancer patient efficiently. Thoracic malignancies including lung cancers and pleural mesothelioma are accountable for little more than 11.6% of the global cancer burden [4]. Mesothelioma is one of the rare cancers, but concern is the incidences are increasing globally. However, the good news is first-line chemotherapy with the combination of immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and mesothelioma has showed promising respond and improved overall survival (OS) in pivotal clinical trials [10]. ICIs are commonly referred as immunotherapy are antigens on the cancer cells, and inhibitors are the antibodies produce by the T cell defence system. By inhibiting immune checkpoints, the cancer cells become visible to be identified as abnormal cells and attack by the body's defence system [17]. The programmed death receptor-1 (PD-1) and programmed death receptor ligand-1 (PD-L1) inhibitors are commonly used immune checkpoint blockers for anti-cancer treatment. PD-1/PD-L1 are proteins produced by immune cells and mimic by cancer cells that are implicated in inhibiting T cell response to regulate our immune system, which results tumour cells escaping the defence mechanism to achieve immune surveillance. Therefore, inhibiting immune checkpoints as well as monoclonal antibodies can lead to effective apoptosis of tumour cells [17]. Mesothelioma is an industrial disease caused by significant asbestos exposure. It is the cancer of the mesothelial tissue which presents in the lining of the mediastinum of pleura, pericardium and peritoneum, most commonly affected sites are pleura of the lung or chest wall lining [9] as route of asbestos exposure is inhalation. Calretinin is a calcium binding protein, typically over exposed in malignant mesotheliomas and the most useful marker even while initial changes take place [5]. On the other hand, Wilm's tumour 1 (WT-1) gene expression on the tumour cells can be related to prognosis as it can elicit immune response, thereby inhibit cell apoptosis. A systematic review and meta-analysis study conducted by Qi et al. has suggested that expression of WT-1 in a solid tumour is fatal however, it gives the tumour cell a feature of immune sensitivity which then acts positively towards the treatment with immunotherapy. Clinical significance of WT-1 oncogene in treatment is still hugely debatable and needs further attention [21]. Recently, Japan has reinstated Nivolumab in patients with chemo-refractory mesothelioma. According to NCCN guidelines, the salvage therapies include Pembrolizumab in PD-L1 pos

Early detection of breast cancer (BC) comprises two approaches: screening of asymptomatic women in a specified target population at risk (usually a target age range for women at average risk), and early diagnosis for women with BC signs and symptoms. Screening for BC is a key health intervention for early detection. While population-based screening programs have been implemented for age-selected women, the pivotal clinical trials have not addressed the global utility nor the improvement of screening performance by utilizing more refined parameters for patient eligibility, such as individualized risk stratification. In addition, with the exception of the subset of women known to carry germline pathogenetic mutations in (high- or moderately-penetrant) cancer predisposition genes, such as BRCA1 and BRCA2, there has been less success in outreach and service provision for the unaffected relatives of women found to carry a high-risk mutation (i.e., "cascade testing") as it is in these individuals for whom such actionable information can result in cancers (and/or cancer deaths) being averted. Moreover, even in the absence of clinical cancer genetics services, as is the case for the immediate and at least near-term in most countries globally, the capacity to stratify the risk of an individual to develop BC has existed for many years, is available for free online at various sites/platforms, and is increasingly being validated for non-Caucasian populations. Ultimately, a precision approach to BC screening is largely missing. In the present chapter, we aim to address the concept of risk-adapted screening of BC, in multiple facets, and understand if there is a value in the implementation of adapted screening strategies in selected women, outside the established screening prescriptions, in the terms of age-range, screening modality and schedules of imaging.

This communication model attempts to reconcile the unknowingness of death, with a deeper inner knowingness that supports End of Life patients in an empowered way, through a mindset that models both oneness and presence with the death and dying experience. Through 23 years of experienced EOL care, I feel it seems necessary to rethink the very one-dimensional idea of dying and to create a space for a multidimensional experience. This model of communication and perspective-taking, offers my patients an opportunity for a secure connection to their own inner resources of knowing how to die. As our bodies are each equipped in our own unique way to do it perfectly, as the return of self, from the experience of being. This communication model also includes perspectives and narratives that attempt to make communication and care in the EOL experience more effortless and intuitive for the provider. Further, the model explains and illustrates why perspectives matter, as they impact connection in the relationship of the provider to the patient and includes a multidimensional perspective to question our own perceptions of death as providers. This model also includes the theory of balance and harmony. As it relates to the relativity of the experience of self, through the connection of communication and perspectives, as the exchange of information that occurs in the relationship between providers and patients. This information as a model represents a new awareness approach in the field of EOL care. It's based on 23 years of EOL experience and is supported through research and a fundamental theory of our reality, which intuitively and logically approaches relativity in our human connection to our patients as providers.

This chapter surveys the range of different orientations toward decision-making, common clinical scenarios, and considerations to bear in mind when caring for culturally diverse patients at the end of life. While this chapter draws on the cultural competency literature, its primary goal is to articulate an approach to end-of-life care that is rooted in cultural humility and structural competency. Medical providers, as representatives of the social institution of medicine, have their own cultural values that often come into conflict with patients' cultural values, especially when patients and providers have different unspoken visions of the "good death," or when patients wish to receive interventions that their providers deem futile. In the final section of the chapter, we seek to move away from this confrontational paradigm by analyzing two case studies of decision-making across cultures in order to empower providers to engage in value-based shared decision-making and thereby achieve goal-concordant care.

An enthusiastic approach to understand Catholic theology and the relativity it has in modern-day healthcare will immediately recognize a connection between the Beatitudes (Matthew 5.) as preached by Jesus Christ and their applications through the principles of Catholic Social Teaching. The latter represents Church doctrine on human dignity and the common good in society. The Beatitudes are a core message of faith and the map to help us return to the presence of our creator, securing our alignment with His purpose for our life. The Beatitudes inspired the saints, who put them into action through the graces they convey. Additionally, the Beatitudes' guidance prepares the faithful followers of Christ to enter eternal joy, "where there is no more pain nor sorrow but eternal life" (Revelation 21:4.). Claiming a multicultural and multinational history of two millennia allows Catholics to connect with time and space that is not only transcendent but well understood intergenerationally in our human experience. With this concept in mind, clinical providers are encouraged to connect with the theological and spiritual Catholic themes in this chapter. Additionally, a correlation to the human experience of universal emotions will be of great benefit in this integrated approach.

PARP inhibitors first entered the clinic in 2003 in combination with DNA damaging agents in an attempt to overcome treatment resistance to established agents. A brief overview of ADP-ribosylator enzyme biology and the early preclinical development of the class is discussed, illustrating the multiple biological activities of these enzymes and potential wider clinical applicability. The chapter then documents those early years of clinical development and the evolution of the field and eventual registration of PARP inhibitors as active anticancer agents in their own right-in genetically vulnerable tumours.

Tumor cells evolve through space and time, generating genetically and phenotypically diverse cancer cell populations that are continually subjected to the selection pressures of their microenvironment and cancer treatment.