Integrative Therapies in Cancer Care: An Update on the Guidelines.

INTRODUCTION: ASCO and the Society for Integrative Oncology have collaborated to develop guidelines for the application of integrative approaches in the management of anxiety, depression, fatigue and use of cannabinoids and cannabis in patients with cancer. These guidelines provide evidence-based recommendations to improve outcomes and quality of life by enhancing conventional cancer treatment with integrative modalities. METHODS: All studies that informed the guideline recommendations were reviewed by an Expert Panel which was made up of a patient advocate, an ASCO methodologist, oncology providers, and integrative medicine experts. Panel members reviewed each trial for quality of evidence, determined a grade quality assessment label, and concluded strength of recommendations. RESULTS: Strong recommendations for management of cancer fatigue during treatment were given to both in-person or web-based mindfulness-based stress reduction, mindfulness-based cognitive therapy, and tai chi or qigong. Strong recommendations for management of cancer fatigue after cancer treatment were given to mindfulness-based programs. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. The recommended modalities for managing anxiety included Mindfulness-Based Interventions (MBIs), yoga, hypnosis, relaxation therapies, music therapy, reflexology, acupuncture, tai chi, and lavender essential oils. The strongest recommendation in the guideline is that MBIs should be offered to people with cancer, both during active treatment and post-treatment, to address depression. CONCLUSION: The evidence for integrative interventions in cancer care is growing, with research now supporting benefits of integrative interventions across the cancer care continuum.

A survey of patients with cancer and oncology health-care professionals about cannabis use during treatment.

BACKGROUND: This study characterizes patient and health-care professional perspectives regarding medical cannabis use at a National Cancer Institute-Designated Cancer Center. Data evaluated included the prevalence and patterns of and reasons for cannabis use. METHODS: Patients with cancer undergoing treatment were recruited into a cross-sectional survey as part of a national National Cancer Institute-funded effort. Participants completed a survey about cannabis use, reasons for use, and types of cannabis. A health-care professional survey was also conducted to explore perspectives regarding patients' use of cannabis. RESULTS: A total of 313 patients with cancer (mean [SD] age = 60.7 [12.8] years) completed the survey (43% response rate) between 2021 and 2022. Of the respondents, 58% were female; identified as White (61%) and Black (23%); and had diverse cancer diagnoses. Nearly half of respondents (43%) had previously used cannabis, one-quarter (26%) had used cannabis since their cancer diagnosis, and almost 1 in 6 (17%) were actively using cannabis at the time of survey completion. The most common modes of ingestion were gummies (33%) and smoking (30%). The most commonly reported reasons for use were insomnia (46%), pain (41%), and mood (39%). For the 164 health-care professionals who completed the survey (25% response rate), the majority agreed that cannabis use (72%) is safe and beneficial for patients (57%). Four in 10 (39%) health-care professionals felt comfortable providing guidance to patients about cannabis use; however, only 1 in 8 (13%) felt knowledgeable about the topic of cannabis. CONCLUSIONS: Approximately one-sixth of patients with cancer receiving treatment actively use cannabis for management of various cancer symptoms. Perceptions about cannabis use and education varied widely among health-care professionals.

Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs. Disruption of NETs by either DNase I treatment or depletion of neutrophils in CRCs attenuated the efficacy of the drug combination. Moreover, NETs were present in tumor biopsies from patients treated with the drug combination in a phase II clinical trial. Increased NET levels in tumors were associated with longer progression-free survival. Mechanistically, the drug combination induced the expression of IL-8 preferentially in PIK3CA-mutant CRCs to attract neutrophils into the tumors. Further, the drug combination increased the levels of ROS in neutrophils, thereby inducing NETs. Cathepsin G (CTSG), a serine protease localized in NETs, entered CRC cells through the RAGE cell surface protein. The internalized CTSG cleaved 14-3-3 proteins, released BAX, and triggered apoptosis in CRC cells. Thus, our studies illuminate a previously unrecognized mechanism by which chemotherapy-induced NETs kill cancer cells.

Perceptions, prevalence, and patterns of cannabis use among cancer patients treated at 12 NCI-Designated Cancer Centers.

BACKGROUND: The legal climate for cannabis use has dramatically changed with an increasing number of states passing legislation legalizing access for medical and recreational use. Among cancer patients, cannabis is often used to ameliorate adverse effects of cancer treatment. Data are limited on the extent and type of use among cancer patients during treatment and the perceived benefits and harms. This multicenter survey was conducted to assess the use of cannabis among cancer patients residing in states with varied legal access to cannabis. METHODS: A total of 12 NCI-Designated Cancer Centers, across states with varied cannabis-access legal status, conducted surveys with a core questionnaire to assess cannabis use among recently diagnosed cancer patients. Data were collected between September 2021 and August 2023 and pooled across 12 cancer centers. Frequencies and 95% confidence intervals for core survey measures were calculated, and weighted estimates are presented for the 10 sites that drew probability samples. RESULTS: Overall reported cannabis use since cancer diagnosis among survey respondents was 32.9% (weighted), which varied slightly by state legalization status. The most common perceived benefits of use were for pain, sleep, stress and anxiety, and treatment side effects. Reported perceived risks were less common and included inability to drive, difficulty concentrating, lung damage, addiction, and impact on employment. A majority reported feeling comfortable speaking to health-care providers though, overall, only 21.5% reported having done so. Among those who used cannabis since diagnosis, the most common modes were eating in food, smoking, and pills or tinctures, and the most common reasons were for sleep disturbance, followed by pain and stress and anxiety with 60%-68% reporting improved symptoms with use. CONCLUSION: This geographically diverse survey demonstrates that patients use cannabis regardless of its legal status. Addressing knowledge gaps concerning benefits and harms of cannabis use during cancer treatment is critical to enhance patient-provider communication.

P53 Activation Promotes Maturational Characteristics of Pluripotent Stem Cell-Derived Cardiomyocytes in 3-Dimensional Suspension Culture Via FOXO-FOXM1 Regulation.

BACKGROUND: Current protocols generate highly pure human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in vitro that recapitulate characteristics of mature in vivo cardiomyocytes. Yet, a risk of arrhythmias exists when hiPSC-CMs are injected into large animal models. Thus, understanding hiPSC-CM maturational mechanisms is crucial for clinical translation. Forkhead box (FOX) transcription factors regulate postnatal cardiomyocyte maturation through a balance between FOXO and FOXM1. We also previously demonstrated that p53 activation enhances hiPSC-CM maturation. Here, we investigate whether p53 activation modulates the FOXO/FOXM1 balance to promote hiPSC-CM maturation in 3-dimensional suspension culture. METHODS AND RESULTS: Three-dimensional cultures of hiPSC-CMs were treated with Nutlin-3a (p53 activator, 10 µM), LOM612 (FOXO relocator, 5 µM), AS1842856 (FOXO inhibitor, 1 µM), or RCM-1 (FOXM1 inhibitor, 1 µM), starting 2 days after onset of beating, with dimethyl sulfoxide (0.2% vehicle) as control. P53 activation promoted hiPSC-CM metabolic and electrophysiological maturation alongside FOXO upregulation and FOXM1 downregulation, in n=3 to 6 per group for all assays. FOXO inhibition significantly decreased expression of cardiac-specific markers such as TNNT2. In contrast, FOXO activation or FOXM1 inhibition promoted maturational characteristics such as increased contractility, oxygen consumption, and voltage peak maximum upstroke velocity, in n=3 to 6 per group for all assays. Further, by single-cell RNA sequencing of n=2 LOM612-treated cells compared with dimethyl sulfoxide, LOM612-mediated FOXO activation promoted expression of cardiac maturational pathways. CONCLUSIONS: We show that p53 activation promotes FOXO and suppresses FOXM1 during 3-dimensional hiPSC-CM maturation. These results expand our understanding of hiPSC-CM maturational mechanisms in a clinically-relevant 3-dimensional culture system.

GDF11 and aging biology - controversies resolved and pending.

Since the exogenous administration of GDF11, a TGF-ß superfamily member, was reported to have beneficial effects in some models of human disease, there have been many research studies in GDF11 biology. However, many studies have now confirmed that exogenous administration of GDF11 can improve physiology in disease models, including cardiac fibrosis, experimental stroke, and disordered metabolism. GDF11 is similar to GDF8 (also called Myostatin), differing only by 11 amino acids in their mature signaling domains. These two proteins are now known to be biochemically different both in vitro and in vivo. GDF11 is much more potent than GDF8 and induces more strongly SMAD2 phosphorylation in the myocardium compared to GDF8. GDF8 and GDF11 prodomain are only 52% identical and are cleaved by different Tolloid proteases to liberate the mature signaling domain from inhibition of the prodomain. Here, we review the state of GDF11 biology, highlighting both resolved and remaining controversies.

Integrative Medicine Program- MD Anderson Cancer Center

The Integrative Medicine Program at MD Anderson Cancer Center was first established in 1998. Our mission is to empower patients with cancer and their families to become active partners in their own physical, psycho-spiritual, and social health through personalized education and evidenced-based clinical care to optimize health, quality of life, and clinical outcomes across the cancer continuum. The program consists of three main components: clinical care, research, and education. The Integrative Medicine Center provides clinical services to patients through individual and group programs. The clinical philosophy of the center is to work collaboratively with the oncology teams to build comprehensive and integrative care plans that are personalized, evidence-based, and safe with the goal of improving clinical outcomes. The individual services comprise of integrative oncology consultation, acupuncture, meditation, music therapy, nutrition, and oncology massage. The center also provides a variety of group programs including meditation, yoga, tai chi, cooking classes and others. Over the past 13 years, over 70,000 patients and families have participated in services and programs offered by the center. The research portfolio focuses on three main areas: mind-body interventions, acupuncture, and meditation. This lecture will focus on providing an overview of the Integrative Medicine Program at MD Anderson with a focus on the clinical services provided. Participants will learn about the integrative clinical model and how this is applied to the care of cancer patients at MD Anderson Cancer Center. Current and future research topics will be discussed as well as patient cases.