Antibody-based immunotherapy for ovarian cancer: where are we at?

Cytoreductive surgery and chemotherapy continue to be the mainstay of ovarian cancer treatment. However, as mortality from advanced ovarian cancer remains very high, novel therapies are required to be integrated into existing treatment regimens. Immunotherapy represents an alternative and rational therapeutic approach for ovarian cancer based on a body of evidence supporting a protective role of the immune system against these cancers, and on the clinical success of immunotherapy in other malignancies. Whether or not immunotherapy will have a role in the future management of ovarian cancer is too early to tell, but research in this field is active. This review will discuss recent clinical developments of selected immunotherapies for ovarian cancer which fulfil the following criteria: (i) they are antibody-based, (ii) target a distinct immunological pathway, and (iii) have reached the clinical trial stage. Specifically, the focus is on Catumaxomab (anti-EpCAM × anti-CD3), Abagovomab, Oregovomab (anti-CA125), Daclizumab (anti-CD25), Ipilimumab (anti-CTLA-4), and MXD-1105 (anti-PD-L1). Catumaxomab has reached phase III clinical trials and exhibits promise with reports, showing that it can cause a significant and sustained reduction in ascites. Phase I–III clinical trials continue to be conducted on the other antibodies, some of which have had encouraging reports. We will also provide our perspective on the future of immunotherapy for ovarian cancer, and how it may be best employed in treatment regimens.     

Will we need lymph node dissection at all in the future?

Traditionally in the treatment of primary breast cancer, axillary lymph node dissection (ALND) plays an important role. However, a substantial and increasing percentage of patients appear to have no nodal involvement and have been subjected to ALND unnecessarily. The first reason to perform an ALND is axillary nodal staging. After reviewing the literature, it can be concluded that in clinically node-negative patients an adequately conducted lymphatic mapping by sentinel node procedure is equal to ALND for this purpose. The second reason to perform an ALND is to establish the extent of nodal involvement, which might have an impact on adjuvant treatment recommendations. However, there is no evidence available that patients with extensive nodal involvement (= 4 positive nodes) benefit more from adjuvant systemic treatment (either standard or high dose) in terms of reduction of odds of recurrence and mortality compared to patients with limited nodal involvement and optimally administered so-called standard adjuvant treatment. The third reason to perform an ALND is to ensure axillary tumor control. Reviewing the different treatment options, it can be concluded that in clinically node-negative patients axillary control after axillary radiotherapy appears to be similar to axillary control after ALND. In clinically overt axillary involvement, ALND (with or without adjuvant radiotherapy) may result in an improved regional control. In the near future, ALND will not be the standard of care but will be reserved for those patients with proven axillary lymph node involvement. In microscopic disease, radiotherapy may be an alternative with equal control and less morbidity.     

Evolved tumor suppression: why are we so good at not getting cancer?

The law of natural selection can be used to understand cancer development at the level of species as well as at the level of cells and tissues. Through this perspective, I seek to explain: (i) Why the lack of sufficient selective pressure to prevent cancers in old age helps explain the exponential increase in cancer incidence in the elderly. (ii) Why the evolution of long-lived animals necessitated the acquisition of potent tumor suppressive mechanisms. (iii) How the requirement to prevent inappropriate somatic cell expansion and cancer has constrained developmental and tissue architectural modalities. (iv) How the evolution of well-adapted stem cells with complex niche requirements has conferred resistance to oncogenic mutations, as phenotype-altering genetic change is almost always disadvantageous within a well-adapted cell population. (v) How the impairment of stem cell fitness, as occurs in old age, can promote selection for adaptive mutations and cancer initiation. (vi) Why differential maintenance of stem cell fitness may explain how different vertebrate species with enormous differences in life span and body size similarly avoid cancer through reproductive years.     

Liquid biopsy and non-small cell lung cancer: are we looking at the tip of the iceberg?

The possibility to analyse the tumour genetic material shed in the blood is undoubtedly one of the main achievements of translational research in the latest years. In the modern clinical management of advanced non-small cell lung cancer, molecular characterisation plays an essential role. In parallel, immunotherapy is widely employed, but reliable predictive markers are not available yet. Liquid biopsy has the potential to face the two issues and to increase its role in advanced NSCLC in the next future. The aim of this review is to summarise the main clinical applications of liquid biopsy in advanced non-small cell lung cancer, underlining both its potential and limitations from a clinically driven perspective.Subject terms: Non-small-cell lung cancer, Tumour biomarkers     

Can we HIIT cancer if we attack inflammation?

Physical exercise offers numerous health-related benefits to individuals with cancer. Epidemiologic research has primarily been concerned with conventional exercise training that aligns with the recommendations of 150 min of moderate to vigorous physical activity per week. These recommendations are safe and effective at improving physical and psychosocial outcomes. Given the extensive evidence for generalized physical activity, researchers have begun to explore novel training regimens that may provide additional health benefits and/or improved adherence. Specifically, exercise at higher intensities may offer more or different benefits than conventional training approaches with potentially profound effects on the tumor microenvironment. This commentary focuses on the physiological effects of high-intensity interval training, also known as “HIIT,” and its potential antineoplastic properties.     

Molecular targeted agents—where we are and where we are going

A total of 23 new cancer medicines or indication expansions were approved by the U. S. Food and Drug Administration in 2012. Among these, 12 are new molecular entities (NMEs)-new chemical or biological drugs approved for the first time for oncologic use-and 10 of these NMEs are molecular targeted agents. Among the 10 targeted agents, 4 are anti-angiogenesis agents and 2 are Bcr-Abl pathway inhibitors, targeting well established targets validated by previously approved agents such as bevacizumab (Avastin) or imatinib (Gleevec). Despite this progress, several questions remain: Do these newly approved agents provide sufficient treatment options to manage the broad spectrum of cancers we deal with in the clinic? Where will the next wave of new cancer drugs come from? Where should R&D efforts be invested to continue improve cancer treatment and management, especially for tumor types uniquely prevalent in China? This editorial and the review articles in this special issue of Chinese Journal of Cancer provide an in depth review of the progress and challenges in developing targeted cancer therapies, as well as an outlook of new research areas where near term breakthroughs are expected to overcome some of these challenges.     

Psycho-oncology: where have we been? Where are we going?

This article reviews the development of the subspeciality of psycho-oncology and its contributions to patient care, encouraging more attention to and research into the care of the total patient: the physical, psychological, social and spiritual aspects of care. The result is enhanced quality of life as the patient is studied in the domains of living that are important, extending across the continuum of care from diagnosis to palliative care. In addition, cancer prevention and early detection depends largely on changing attitudes and behaviours that put people at greater risk. This is an important area of research for psycho-oncologists. In the past two decades, research has contributed to our understanding of the psychological responses that accompany a cancer diagnosis. Oncologists better recognise psychological distress and psychiatric disorders such as anxiety, depression and delirium (in hospitalised patients) as frequent comorbid disorders. The development of valid assessment tools for the patients' self-report has been important. Increasingly, outcome measures in controlled trials of new therapies include quality of life, and no longer look at survival alone. The future will continue to bring new challenges to psycho-oncology as patients face new challenges in treatment. A major aim of the next century will be to bring this integrated approach to all patients in an affordable manner.     

A systematic review of surgical biopsy for LCIS found at core needle biopsy – Do we have the answer yet?

Background

The natural history of lobular carcinoma in-situ (LCIS) suggests that women are at increased risk of subsequent invasive breast cancer. Questions of effective management for women with this lesion have led to the need for evidence-based guidance and, in particular, guidance regarding management after LCIS is found at core needle biopsy (CNB).

Methods

A systematic review was conducted to determine the most appropriate management for women with LCIS found at CNB. A comprehensive search of the scientific literature was conducted to identify the literature pertaining to this population. Critical appraisal of the literature, data extraction and a narrative synthesis of the results were conducted. The outcome of interest was upgrade of diagnosis to invasive breast cancer or ductal carcinoma in-situ (DCIS).

Results

Sparse data, with limited generalisability and considerable uncertainty, are available for women with LCIS at CNB. Nine studies were identified that met pre-specified inclusion criteria. The reported estimates of upgrade of diagnosis from LCIS to invasive breast cancer or DCIS ranged from 2% to 25%. The body of evidence was limited by its retrospective nature, risk of selection bias and poor generalisability to all women with LCIS at CNB. Further, higher quality research is required to determine the best approach for women with LCIS at CNB with any certainty.