Cancer derives from a cell clone that has accumulated genetic and epigenetic changes that influence its phenotype and finally enable it to escape from the normal controls of proliferation. A recent paper shows that, in myc‐induced tumours, the inactivation of this oncogene produces the regression of the tumours and the differentiation of the tumour cells into mature osteocytes.1 In addition, a further reactivation of myc in these cells does not restore the malignant phenotype but induces apoptosis. This discovery could (...) lead to an innovative therapeutic strategy. BioEssays 25:104–107, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Over the past few years several drugs that target epigenetic modifications have shown clinical benefits, thus seemingly validating epigenetic cancer therapy. More recently, however, it has become clear that these drugs are either characterized by low specificity or that their target enzymes have low substrate specificity. As such, clinical proof‐of‐concept for epigenetic cancer therapies remains to be established. Human cancers are characterized by widespread changes in their genomic DNA methylation and histone modification patterns. Epigenetic cancer (...) class='Hi'>therapy aims to restore normal epigenetic modification patterns through the inhibition of epigenetic modifier enzymes. In this review, we provide an overview about the known functional roles of DNA methyltransferases, histone deacetylases, histone methyltransferases, and demethylases in cancer development. The available data identify several examples that warrant further consideration as drug targets. Future research should be directed toward targeted enzyme inhibition and toward exploring interactions between epigenetic pathways to maximize cancer specificity. (shrink)

MYC is a transcription factor, which not only directly modulates multiple aspects of transcription and co‐transcriptional processing (e.g. RNA‐Polymerase II initiation, elongation, and mRNA capping), but also indirectly influences several steps of RNA metabolism, including both constitutive and alternative splicing, mRNA stability, and translation efficiency. As MYC is an oncoprotein whose expression is deregulated in multiple human cancers, identifying its critical downstream activities in tumors is of key importance for designing effective therapeutic strategies. With this knowledge and recent technological advances, (...) we now have multiple angles to reach the goal of targeting MYC in tumors, ranging from the direct reduction of MYC levels, to the dampening of selected house‐keeping functions in MYC‐overexpressing cells, to more targeted approaches based on MYC‐induced secondary effects. (shrink)

Histone deacetylase inhibitors (HDACi) are in clinical trials against a variety of cancers. Despite early successes, results against the more common solid tumors have been mixed. How is it that so many cancers, and most normal cells, tolerate the disruption caused by HDACi‐induced protein hyperacetylation? And why are a few cancers so sensitive? Here we discuss recent results showing that human cells mount a coordinated transcriptional response to HDACi that mitigates their toxic effects. We present a hypothetical signaling system that (...) could trigger and mediate this response. To account for the existence of such a response, we note that HDACi of various chemical types are made by a variety of organisms to kill or suppress competitors. We suggest that the resistance response in human cells is a necessary evolutionary consequence of exposure to environmental HDACi. We speculate that cancers sensitive to HDACi are those in which the resistance response has been compromised by mutation. Identifying such mutations will allow targeting of HDACi therapy to potentially susceptible cancers. (shrink)

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, (...) has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

During tumor evolution, cancer cells use the tumor‐stroma crosstalk to reorganize the microenvironment for maximum robustness of the tumor. The success of immune checkpoint therapy foretells a new cancer therapy paradigm: an effective cancer treatment should not aim to influence the individual components of super complex intracellular interactomes (molecular targeting), but try to disrupt the intercellular interactions between cancer and stromal cells, thus breaking the tumor as a whole. Arguments are provided in favor of (...) a hypothesis that such interactions include formation of synapse‐like structures (interfaces) where the interacting cells are located at a distance of ∼10–15 nm. Within these interfaces, molecules initiating and strengthening the interaction are organized, and allow optimum cross‐signaling; a very confined intercellular space facilitates the concentration of secreted cytokines, enhancing the paracrine cross‐communication. These features of tumors form a druggable cancer hallmark the tumor‐stroma symbiotic crosstalk—which represents a new target for efficient cancer drug discovery. (shrink)

While a number of valid molecular targets have been discovered for tumours over the past decade, finding an effective way of delivering therapeutic genes specifically to tumours has proved more problematic. A variety of viral and non‐viral delivery vehicles have been developed and applied in anti‐cancer gene therapies. However, these suffer from either inefficient and/or short‐lived gene transfer to target cells, instability in the bloodstream and inadequate tumour targeting. Recently, various types of non‐pathogenic obligate anaerobic and facultative anaerobic bacteria (...) have been shown to infiltrate and selectively replicate within solid tumours when delivered systemically. This has prompted the development of cancer gene therapy protocols that use such bacteria as gene delivery vehicles. Here, we review the evidence for the success of these in pre‐clinical models and clinical trials, as single modality treatments and in combination with conventional cancer therapies. BioEssays 28:84–94, 2006. © 2005 Wiley Periodicals, Inc. (shrink)

High‐molecular‐weight hyaluronan acts as a ligand of the tumor‐suppressive Hippo signal, whereas degradation of hyaluronan from a high‐molecular‐weight form to a low‐molecular‐weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro‐oncogenic transcriptional coactivator yes‐associated protein (YAP), which creates a cancer‐predisposing microenvironment and drives neoplastic transformation of cells through both cell‐autonomous and non‐cell‐autonomous mechanisms. In fact, accumulation of low‐molecular‐weight hyaluronan in tissue stroma is observed in many types of cancers. Since inhibition of YAP activity suppresses tumor (...) growth in vivo, pharmacological intervention of the Hippo‐YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo‐YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors. (shrink)

It has been known for long time that the cosmic sound wave was there since the early epoch of the Universe. Signatures of its existence are abound. However, such an acoustic model of cosmology is rarely developed fully into a complete framework from the notion of space, cancer therapy up to the sky. This paper may be the first attempt towards such a complete description of the Universe based on classical wave equation of sound. It is argued that (...) one can arrive at a consistent description of space, elementary particles, Sachs-Wolfe acoustic theorem, up to a novel approach for cancer therapy, starting from this simple classical wave equation of sound. We also discuss a plausible extension of Acoustic Sachs-Wolfe theorem based on its analogue with Klein-Gordon equation to become Acoustic Sachs-Wolfe-Christianto-Smarandache-Umniyati (ASWoCSU) equation. It is our hope that the new proposed equation can be verified with observation data. But we admit that our model is still in its infancy, more researches are needed to fill all the missing details. (shrink)

Despite advances in treatments over the last decades, a uniformly reliable and free of side effects therapy of human cancers remains to be achieved. During chromosome replication, a premature halt of two converging DNA replication forks would cause incomplete replication and a cytotoxic chromosome nondisjunction during mitosis. In contrast to normal cells, most cancer cells bear numerous DNA deletions. A homozygous deletion permanently marks a cell and its descendants. Here, we propose an approach to cancer therapy (...) in which a pair of sequence‐specific roadblocks is placed solely at two cancer‐confined deletion sites that are located ahead of two converging replication forks. We describe this method, termed “replication blocks specific for deletions” (RBSD), and another deletions‐based approach as well. RBSD can be expanded by placing pairs of replication roadblocks on several different chromosomes. The resulting simultaneous nondisjunctions of these chromosomes in cancer cells would further increase the cancer‐specific toxicity of RBSD. (shrink)

The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS‐STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA‐dependent protein kinase (DNA‐PK) complex, that recently emerged as an activator of inflammatory responses in tumour (...) cells. We propose that stratification analyses on cGAS and DNA‐PK expression/activation status should be carried out to predict treatment efficacy. We herein also provide insights into non‐canonical functions borne by cGAS and cGAMP, highlighting how they may influence tumourigenesis. All these parameters should be taken into consideration concertedly to choose strategies aiming to effectively boost tumour immunogenicity. (shrink)

The NANOCAN project aims to enhance our understanding of the behavior of nanomaterials in the body, focusing on biodegradable nanoparticles for cancer diagnostics, and targeted cancer drug delivery. There is a range of available and potentially useful nanoparticles and drugs that might be of interest to such a project. In this paper, we make values implied in—and relevant to—choices between these alternatives explicit, thereby offering a case study of how values enter research processes in this area. From a (...) project centered perspective, we observe that values often play their role implicitly, as a result of funding incentives, regulations, and structural and organizational features of the research process. Based on our observations and categorization of relevant values, we turn to a broader discussion of how responsible research and innovation can be facilitated by making value priorities, value conflicts, and biases explicit targets of normative assessment. (shrink)

A new therapeutic strategy could break the stalemate in the war on cancer by targeting not all cancerous cells but the small fraction that lie at the root of cancers. Lucie Laplane offers a comprehensive analysis of cancer stem cell theory, based on an original interdisciplinary approach that combines biology, biomedical history, and philosophy.

ObjectiveHormone positive breast cancer patients bear side effects of endocrine therapy and that may be related to depression and anxiety. We sought to find an association between mental health and side effects of endocrine therapy.MethodsA total of 398 patients participated. Sociodemographic, disease profile, and side effects questionnaires were administered. We screened for depressive and anxiety disorders by using the SDS and SAS.ResultsThe prevalence of depression and anxiety in our study were 33.4% and 13.3%, respectively. Depression was linked (...) to education level, night sweats, vaginal dryness, and fatigue ; anxiety was associated with education level, time to diagnosis, osteopenia, loss of hair, and fatigue. A stratified analysis according to age was performed as an exploratory. None of factor-age interactions was statistically significant.ConclusionSide effects of endocrine therapy were significantly associated with anxiety and depression. Side effects deserve greater emphasis and clinical interventions are needed to reduce anxiety and depression in breast cancer patients accepting ET. (shrink)

Tumor‐infiltrating lymphocyte (TIL) therapy is a promising approach for treating refractory or advanced solid cancers by using autologous TILs harvested from cancer tissues. Despite the heterogeneity of cancer, TIL therapy can potentially produce a positive therapeutic response, including complete remission.After decades of research on lymphocyte functions, culture/expansion methods, therapeutic protocols, and multiple clinical trials, TIL therapy has finally reached a stage where it can be formally approved for clinical use.TIL therapy is expected to hold (...) a unique position among anti‐cancer therapeutic options as a standard intervention. To successfully introduce TIL therapy into clinical settings, there is a need to expand therapeutic indications and set up the best protocols for cancer tissue sampling and manufacturing, and related clinical trials. Moreover, studies on next‐generation TIL therapy have already begun, and post‐approval real‐world data will promote and support further research. (shrink)

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target‐the‐weakness strategy. Our most detailed example involves the immune system. The absence (...) of adaptive immunity in immunosuppressed tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target‐the‐weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. (shrink)

The presence and role of microbes in human cancers has come full circle in the last century. Tumors are no longer considered aseptic, but implications for cancer biology and oncology remain underappreciated. Opportunities to identify and build translational diagnostics, prognostics, and therapeutics that exploit cancer's second genome—the metagenome—are manifold, but require careful consideration of microbial experimental idiosyncrasies that are distinct from host‐centric methods. Furthermore, the discoveries of intracellular and intra‐metastatic cancer bacteria necessitate fundamental changes in describing clonal (...) evolution and selection, reflecting bidirectional interactions with non‐human residents. Reconsidering cancer clonality as a multispecies process similarly holds key implications for understanding metastasis and prognosing therapeutic resistance while providing rational guidance for the next generation of bacterial cancer therapies. Guided by these new findings and challenges, this Review describes opportunities to exploit cancer's metagenome in oncology and proposes an evolutionary framework as a first step towards modeling multispecies cancer clonality. Also see the video abstract here: https://youtu.be/-WDtIRJYZSs. (shrink)

Drugs targeting a single TK/RTK in the treatment of solid cancers has not had the same success seen in blood cancers. This is, in part, due to acquired resistance in solid cancers arising from a range of mechanisms including the upregulation of compensatory RTK signalling. Rather than attempting to inhibit individual compensatory RTK—requiring knowledge of which RTKs are upregulated in any given tumour—strategies to universally inhibit signalling from multiple RTKs may represent an effective alternative. Endosomal trafficking of RTKs is a (...) common conduit that can regulate signalling from multiple RTKs simultaneously. As such, we posit that targeting endosomal trafficking—in particular, aberrant post‐translational modifications in cancers that contribute to dysregulated endosomal trafficking—could inhibit oncogenic signalling driven by multiple RTKs and pave the way for the development of a novel class of inhibitors that shift the trafficking of RTKs to inhibit tumour growth. (shrink)

This study used historical research methodology to assess the work of US nurses caring for patients with cancer from 1920 to 1950. Primary sources, obtained from several US archives, included nursing procedure books, student nurses’ lecture notes, hospital and nursing annual reports, and meeting minutes. Secondary sources included journal articles and textbooks. The aim was to document the clinical work of nurses caring for patients with cancer and assess this work for evidence of emerging specialization in cancer (...) nursing. Following a review of cancer in the 1920s, nursing education specific to cancer, nursing care related to specific cancer therapies, and the practice of concealing a diagnosis of cancer, were examined. Nurses were consistently educated in cancer nursing, but their cancer education became more focused over the decades. Nurses were closely involved with cancer patients as they monitored their patients’ radium or assisted patients following radical surgery. The issue of concealing the diagnosis of cancer was problematic to some nurses. This paper reveals the nature of nurses’ hospital work with cancer patients and demonstrates a core body of cancer nursing knowledge. The emergence of cancer nursing as a specialty is presented. (shrink)

Chemotherapy is one of the most common treatments used in cancer therapy despite its serious side effects, which remain a huge concern. To the most common side effects include memory and concentration problems as well as changes in taste. This paper presents a very preliminary study focusing on cognitive dysfunction after chemotherapy in breast cancer. This phenomenon, called Cancer-Related Cognitive Dysfunction, is a frequent occurrence. The obtained results prove the impact of chemotherapy on the participant’s ability (...) to concentrate. The QEEG method and digital data analysis were used as the measurement methods. (shrink)

Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro‐environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin complex (...) 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. (shrink)

IntroductionDignity therapy is brief psychotherapy targeting psychological and existential suffering among patients with a life-limiting illness. Studies have been conducted on the use of DT by healthcare professionals. In Italy, the current legislation defines that any form of psychotherapy may be performed exclusively by psychotherapists. Consequently, this intervention is unlikely to be used by other healthcare professionals. Herein, we will describe a training on DT not as a psychotherapy intervention but as a narrative intervention for non-psychotherapists health care professionals. (...) Finally, we will explore the potential enablers/barriers as experienced by palliative care physicians and nurses.MethodsThe study was conducted in the Psycho-Oncology Unit within the Cancer Research Hospital of Reggio Emilia. It consisted of an exploratory qualitative case study. Data were collected employing observations and interview data and thematically analyzed.ResultsThe training was attended by six physicians and ten nurses and took place during two-afternoon sessions for 10 h. Two participants put their training into practice and administered DT under the supervision of a psychotherapist. Data analysis highlighted five overarching themes relating to the training experience and direct use of DT, namely, time required, psychological skills, patient’s disease awareness, patient’s life history, and distinguishing DT from Advance Care Planning.ConclusionPalliative care professionals found DT to be a valuable non-pharmacological hospital-based intervention to address the person beyond the patient and his clinical conditions. In our experience, considering that in Italy, psychotherapy is an intervention that psychotherapists can only perform, it can help organize different training on DT for psychotherapists and other healthcare professionals. (shrink)

The development of cancer therapies is a long and arduous process. Because it can take several years for a cancer agent to pass clinical testing and be approved for use, terminal cancer patients rarely have the time to see these experimental therapies become widely available. For most terminal cancer patients the only opportunity they have to access an experimental drug that could potentially improve their prognosis is by joining a clinical trial. Unfortunately, several aspects of clinical (...) trial methodology that are set in place in order to optimise drug development for the benefit of future generations of cancer patients, pose significant limitations to current patient participation. Therefore, several terminal cancer patients believe that they should have the right to access experimental agents that have passed initial safety testing without having to participate in clinical trials. However, granting off-trial access to patients could be detrimental to the scientific process of drug development, and thus could pose significant risks to the health of future patients relying on sound research. Examining this matter through two divergent ethical lenses, rights-based ethics and communitarian ethics, may provide new insight into the issues surrounding the balance between the autonomous rights of current terminal cancer patients, and the needs of future patients and the values of society. (shrink)

General theories are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality-inhibition, and ‘acausal’ recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy and (...) selectivity ; if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions, potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable. A reductionist General Theory of Cancer Targets is presented, proposing that all good targets are based either on causality-inhibition, or recognition; essential tasks emerge differently in each case. Sophisticated hybrids may provide additional benefit. General theory analysis, including target fragmentation concepts, provides deeper insights into therapeutic mechanisms. (shrink)

Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self‐renewal and give rise to bulk populations of non‐tumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using marker‐specific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to (...) cancer therapeutic resistance and clinical tumor progression. Importantly, proof‐of‐principle for the potential therapeutic utility of the CSC concept has recently been provided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC‐targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC. (shrink)

Este trabajo presenta como objetivo revelar la influencia de los contextos socioeconómicos en las maneras de afrontamiento al cáncer como enfermedad. Se muestra un análisis sobre el cáncer como problema social y de salud; se analiza el papel de algunos entes sociales involucrados, el acceso de los enfermos a las terapias y de los productores de fármacos a las nuevas tecnologías. Se reflexiona acerca de la sobreevaluación de los fármacos que dificulta el acceso a novedosas y efectivas terapias; la supeditación (...) del saber tecnocientífico a los intereses del capital; la creciente contaminación ambiental como detonante al incremento de casos; y la escasez de tecnologías para la prevención y el saneamiento en países subdesarrollados. Finalmente se refiere el programa cubano de lucha contra el cáncer, su situación actual y proyecciones. This paper aimes at revealing the influence of the socioeconomic contexts on the way cancer is faced as a disease. An analysis about cancer as a social and health problem is presented; the role of some social organizations involved the sick's access to therepies and drug producers' access to new technologies. It is reflected on the over-asessment of drugs which makes access to new and effective therapies difficult; the subordination of the technoscientific knowledge to the interests of the capital; the growing environmental pollution as a trigger for cases increase; and the limited technological resources for prevention and cleanup in underdeveloped countries. Finally, it is made reference to the Cuban cancer fighting program, its current status and scope. (shrink)

Hereditary breast and ovarian cancers are frequently attributed to germline mutations in the tumor suppressor genes BRCA1 and BRCA2. BRCA1/2 act to repair double‐strand breaks (DSBs) and suppress the demise of unstable replication forks. Our work elucidated a dynamic interplay between BRCA2 and the WRN DNA helicase/exonuclease defective in the premature aging disorder Werner syndrome. WRN and BRCA2 participate in complementary pathways to stabilize replication forks in cancer cells, allowing them to proliferate. Whether the functional overlap of WRN and (...) BRCA2 is relevant to replication at gaps between newly synthesized DNA fragments, protection of telomeres, and/or metabolism of secondary DNA structures remain to be determined. Advances in understanding the mechanisms elicited during replication stress have prompted the community to reconsider avenues for cancer therapy. Insights from studies of PARP or topoisomerase inhibitors provide working models for the investigation of WRN's mechanism of action. We discuss these topics, focusing on the implications of the WRN‐BRCA2 genetic interaction under conditions of replication stress. (shrink)

In the nearly 40 years since implementation of federal regulations governing the protection of human participants in research, the number of clinical studies has grown exponentially. These studies have become more complex, with multisite trials now common, and there is increasing use of archived biospecimens and related data, including genomics data. In addition, growing emphasis on targeted cancer therapies requires greater collaboration and sharing of research data to ensure that rare patient subsets are adequately represented. Electronic records enable more (...) extensive data collection and mining, but also raise concerns about the potential for inappropriate or unauthorized use of data, bringing patient protections into a new landscape. There are also long-standing concerns about the processes and forms used to obtain informed consent from patients participating in clinical studies. These changes and challenges raise new ethical and practical questions for the oversight of clinical studies, and for protecting patients and their health information in an efficient manner that does not compromise the progress of biomedical research. Contemporary Issues for Protecting Patients in Cancer Research is the summary of a workshop convened by the National Cancer Policy Forum of the Institute of Medicine in February 2014 to explore contemporary issues in human subjects protections as they pertain to cancer research, with the goal of identifying potential relevant policy actions. Clinical researchers, government officials, members of Institutional Review Boards, and patient advocates met to discuss clinical cancer research and oversight. This report examines current regulatory provisions that may not adequately protect patients or may be hindering research, and discusses potential strategies and actions to address those challenges. (shrink)

The ArgumentPatients suffering from advanced, incurable cancer often receive from their doctors proposals to enroll in a clinical trial of an experimental therapy. Experimental therapies are increasingly perceived not as a highly problematic approach but as a near-standard way to deal with incurable cancer. There are, however, important differences in the diffusion of these therapies in Western countries. The large diffusion of experimental therapies for malignant disease in the United States contrasts with the much more restricted diffusion (...) of these therapies in the United Kingdom. The difference between the two reflects differences in the organization of health care in these countries and distinct patterns of the professionalization of medical oncology in America and in Britain. The high density and great autonomy of medical oncologists in the United States encourages there the diffusion of experimental therapies (regarded by some as expensive and inefficient); the lower density of these specialists in the United Kingdom and their task as consultants and not primary caregivers, favors the choice of more conservative (for some, too conservative) treatments. Theoretically, the decision as to whether patients suffering from advanced, incurable cancer will be steered toward an experimental therapy or toward palliative care depends on the values and beliefs of these patients and their physicians. In practice, however, such choice does not depend exclusively on the individual' cultural background and ethical values, but is also strongly affected by the — culturally conditioned — Professional and institutional structure of medicine. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Bringing Cancer Care to Those who Don't Have ItLawrence N. ShulmanI have been treating cancer patients in the Harvard Medical School hospitals since 1977, and in those 35 years we have made tremendous progress. Though work still needs to be done, and far too many patients still die of cancer, many are cured. In particular, children and young adults have a high rate of cure from (...) such diseases as Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and childhood sarcoma. Patients with breast cancer in the US have a greater than 80% chance for long-term survival. The death rate from cervical cancer in the US is very low. These results have been achieved by making diagnoses earlier, in many cases surgical excision, and often systemic therapies such as chemotherapy, hormonal therapy, radiation therapy, and more recently by using so-called "targeted" therapies—those directed at particular molecular characteristics of the cancer cells.Princess Dina Mired has said that the opportunity to survive cancer should not be an accident of geography. In cases where we already have effective and inexpensive tools to cure cancer, these treatments should be considered a basic human right, a life-saving medical service.I met Patty, a young woman living in the U.S. during November of her senior year in high school, after she discovered a small lump above her left collar bone. Though she felt entirely well, she called her primary care doctor who saw her the next day, felt the enlarged lymph node, and referred her to a surgeon, who did a biopsy later that week. Her primary care doctor also called me, and we scheduled a visit when the pathology results were available. The following week the pathologist notified Patty's pediatrician that the biopsy showed Hodgkin's lymphoma. When I met Patty, she was a bright and focused young woman, waiting to hear about her college applications and enjoying her senior year. Her cancer diagnosis was completely out of context with her life as she planned it, but with the support of her family and boyfriend, she seemed prepared to take things one step at a time. A PET CT scan demonstrated a modest mass in the mediastinum (chest), but no other disease. She was in an early stage of the disease with an excellent prognosis. We recommended and administered six months of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine—four chemotherapy agents that are off-patent, and relatively inexpensive. She lost her hair, not a trivial issue for her, but otherwise felt reasonably well during the treatment. She was determined to graduate with her classmates, and was able continue to attend school and keep up with her work. In June, seven months into her cancer diagnosis and treatment, she graduated with honors, and was on track to enroll in college in September.Like other 18-year-old women with Hodgkin's lymphoma, Patty had an over 80% chance for cure with the potential for a long and productive life ahead of her because we could perform a biopsy, make a diagnosis, and safely and effectively treat her with four inexpensive, off-patent, chemotherapy drugs. She had nearly the same likelihood of living a long and fruitful life as her classmates, and had the same chances for childbearing. In my line of work, with the knowledge we now possess, to allow someone like Patty to die without a chance of curative care is simply unacceptable. Treatment of curable cancers should be considered on par with the right to clean water, adequate nutrition, treatment for infectious disease, and access to maternal and child healthcare services.But in many places in the world, people with cancers we could easily eradicate in Boston have no access to cancer services, and do die unnecessarily. The local healthcare infrastructure has no [End Page E10] capacity to evaluate a patient, perform or process a biopsy, make a diagnosis, or treat the patient with potentially curative surgery, chemotherapy and radiation. I have rounded on the wards of hospitals in developing countries, stopping to talk with numerous patients like Patty: young women, some of whom might have had Hodgkin's lymphoma, but no... (shrink)

Rationing in healthcare remains very much a taboo topic. Before COVID-19, it rarely received public attention, even when it occurred in everyday practices, mainly in the form of implicit rationing, as it continues to do today. There are different definitions, types and levels of healthcare rationing, according to different perspectives. With the aim of contributing to a more coherent debate on such a highly emotional healthcare issue as rationing, here are provided a number of reflections from a patient advocate perspective (...) which are specifically focused on bedside rationing, the most troublesome level, both for patients and clinicians, particularly in regard to cancer care. Oncology, with its numerous expensive therapies and increasing number of patients, is undeniably one of the main areas contributing to the increase in healthcare costs. However, the fixed budgets of today's publicly financed health systems cannot allow unlimited access to the potentially beneficial treatments to all patients. Bedside rationing constitutes the last phase of many decision-making processes occurring at different interrelated levels (macro-levels), both inside and outside healthcare systems, which implicitly and inevitably result in a bottleneck determined by the upstream decisions themselves. Shifting from implicit to explicit bedside rationing essentially means moving from a paternalistic to a citizen-before-patient approach; this implies, first of all, a cultural change. Practical bedside rationing is an ethically complex topic, but one that needs to be urgently addressed in a transparent and open debate. In this scenario, the oncological community – patients, patient advocates and clinicians – can and should play an important role. (shrink)

Death from cancer is usually due to metastasis. Fortunately, most cells that escape from a primary tumor fail to form metastases. Identifying reasons for this failure will help development of anti‐metastatic therapies. Intravital videomicroscopy (IVVM) can be used to observe cancer cells injected into live animals. Co‐injected microspheres can be used to assess cell survival. These techniques have been used to show that circulating tumor cells generally arrest in the microcirculation and may extravasate with high efficiency. While many (...) tumor cells may survive in a secondary site, only a small subset form micrometastases and only a subset of these micrometastases persist to form vascularized macrometastases. Furthermore, solitary tumor cells may remain dormant for long periods of time in secondary sites. These findings suggest that metastatic growth and angiogenesis are prime targets for anti‐metastatic therapy. BioEssays 24:885–893, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Over the past decades, anti-cancer treatments have evolved rapidly from cytotoxic chemotherapies to targeted therapies including oral targeted medications and injectable immunooncology and cell therapies. New anti-cancer medications come to markets at increasingly high prices, and health insurance coverage is crucial for patient access to these therapies. State laws are intended to facilitate insurance coverage of anti-cancer therapies.Using Massachusetts as a case study, we identified five current cancer coverage state laws and interviewed experts on their perceptions (...) of the relevance of the laws and how well they meet the current needs of cancer care given rapid changes in therapies. Interviewees emphasized that cancer therapies, as compared to many other therapeutic areas, are unique because insurance legislation targets their coverage. They identified the oral chemotherapy parity law as contributing to increasing treatment costs in commercial insurance. For commercial insurers, coverage mandates combined with the realities of new cancer medications — including high prices and often limited evidence of efficacy at approval — compound a difficult situation. Respondents recommended policy approaches to address this challenging coverage environment, including the implementation of closed formularies, the use of cost-effectiveness studies to guide coverage decisions, and the application of value-based pricing concepts. Given the evolution of cancer therapeutics, it may be time to evaluate the benefits and challenges of cancer coverage mandates. (shrink)

ObjectivesThe breast cancer stigma affects Health-related quality of life, while general resilience resources, namely, sense of coherence, social support, and coping skills, are thought to alleviate this effect. The study aimed to explore the mediating/moderation role of GRRs in the relationship between stigma and HRQoL and its dimensions in Iranian patients with breast cancer.MethodsIn this cross-sectional study, Stigma Scale for Chronic Illness 8-item version, SOC-13, Medical Outcome Survey- Social Support Scale, Brief COPE, and Functional Assessment of Cancer (...) Therapy-Breast were investigated in a convenience sample of Iranian women with confirmed non-metastatic breast cancer. Following the establishment of correlations using Pearson’s correlation, single and parallel mediation analysis and moderation analysis were conducted to determine the extent to which each GRR might be impacted by stigma or decrease the adverse impact of stigma on HRQoL.ResultsAn analysis of 221 women with the mean age of 47.14 showed that stigma was negatively correlated to all HRQoL’s dimensions, SOC, social support, and the bulk of coping skills. In the single mediation analysis, stigma affected all facets of SOC, all subscales of social support, and positive reframing, which partially reduced breast cancer HRQoL. Stigma affects general HRQoL through damaging meaningfulness, social support, and positive reframing. Meaningfulness was marked as the most impacted GRR in terms of all domains of HRQoL. In parallel mediation, reduced meaningfulness, total social support, and positive reframing were highlighted as the pathways of diminished breast cancer HRQoL. Moderation analysis indicated the higher levels of humor, behavioral disengagement, and use of instrumental support behaviors to be functional in protecting different dimensions of HRQoL, while the results were mixed for venting, especially in patients with mastectomy surgery.ConclusionWhile GRRs may be impacted by stigma, they exert a relatively small protective effect against the impact of stigma on HRQoL. This study provides some novel findings, but longitudinal studies are needed to further verify these before any causal conclusion or recommendations for health policy can be drawn. (shrink)

Human cancers comprise an heterogeneous array of diseases with different progression patterns and responses to therapy. However, they all develop within a host context that constrains their natural history. Since it occurs across the diversity of organisms, one can conjecture that there is order in the cancer multiverse. Is there a way to capture the broad range of tumor types within a space of the possible? Here we define the oncospace, a coordinate system that integrates the ecological, evolutionary (...) and developmental components of cancer complexity. The spatial position of a tumor results from its departure from the healthy tissue along these three axes, and progression trajectories inform about the components driving malignancy across cancer subtypes. We postulate that the oncospace topology encodes new information regarding tumorigenic pathways, subtype prognosis, and therapeutic opportunities: treatment design could benefit from considering how to nudge tumors toward empty evolutionary dead ends in the oncospace. (shrink)

We have rapidly gained insights into the presence and function of T lymphocytes in non‐lymphoid tissues, the tissue‐resident memory T (TRM) cells. The central pillar of adaptive immunity has been expanded from classic central memory T cells giving rise to progeny upon reinfection and effector memory cells circulating through the blood and patrolling the tissues to include TRM cells that reside and migrate inside solid organs and tissues. Their development and maintenance have been studied in detail, providing exciting clues on (...) how their unique properties used to fight infections may benefit therapies against solid tumors. We provide an overview of CD8 TRM cells and the properties that make them of interest for vaccination and cancer therapies. (shrink)

Since the dawn of molecular biology, cancer therapy has focused on druggable targets. Despite some remarkable successes, cell‐level evolution remains a potent antagonist to this approach. We suggest that a deeper understanding of the breakdown of cooperation can synergize the evolutionary and druggable‐targets approaches. Complexity requires cooperation, whether between cells of different species (symbiosis) or between cells of the same organism (multicellularity). Both forms of cooperation may be associated with nutrient scarcity, which in turn may be associated with (...) a chemiosmotic metabolism. A variety of examples from modern organisms supports these generalities. Indeed, mammalian cancers—unicellular, glycolytic, and fast‐replicating—parallel these examples. Nutrient scarcity, chemiosmosis, and associated signaling may favor cooperation, while under conditions of nutrient abundance a fermentative metabolism may signal the breakdown of cooperation. Manipulating this metabolic milieu may potentiate the effects of targeted therapeutics. Specific opportunities are discussed in this regard, including avicins, a novel plant product. (shrink)

Graphical AbstractCurrent differentiation therapies for cancer may not be effective because it might not be enough to only use molecules targeting chromatin remodelers. It may also be necessary to stabilize the re-expressed genes to convert malignant cells into benign ones.

Adaptation and stress are two main concepts useful for better understanding the phases of illness and health-related human behavior. The two faces of adaptation, adaptation as a process and adaptation as a product, have raised the question of how long the adaptation process will take in cancer trajectories. The care setting transition from clinical-based into home-based cancer care has stressed the role of family caregivers (FCG) in cancer management. This study examines how types of demanded healthcare information (...) affect the FCG’s role in catalyzing the adaptation of female cancer patients. The mindsponge theory was used in conceptual development and results interpretation. Bayesian Mindsponge Framework (BMF) analytics was used for statistical analysis on a dataset of 48 spouses (husbands) and 12 other family members in five congested communities of Surabaya, Indonesia. Results showed that among the six types of demanded healthcare information, FCGs with a higher tendency to demand cancer-specific information are more likely to need support in catalyzing the adaptation of female cancer patients. Meanwhile, FCGs with a higher demand for information on alternative therapies are less likely to need support in catalyzing cancer adaptation. Other types of healthcare information have ambiguous effects on the need for support in cancer adaptation assistance. This study reveals that the demanded cancer-specific information, e.g., cancer’s prognosis or likely outcome, must be prioritized to assist FCG’s role in catalyzing adaptation among female cancer patients. Cancer prognosis and outcomes reflect the future of cancer care results. (shrink)