NCCN Guidelines® Insights: Hodgkin Lymphoma, Version 2.2022.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte-predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.

NCCN Guidelines® Insights: Palliative Care, Version 2.2021.

Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members' clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel's recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.

Pediatric Hodgkin Lymphoma, Version 3.2021.

Hodgkin lymphoma (HL) is a highly curable form of cancer, and current treatment regimens are focused on improving treatment efficacy while decreasing the risk of late effects of treatment. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric HL provide recommendations on the workup, diagnostic evaluation, and treatment of classic HL, including principles of pathology, imaging, staging, systemic therapy, and radiation therapy. This portion of the NCCN Guidelines focuses on the management of pediatric classic HL in the upfront and relapsed/refractory settings.

Defects in Emerin-Nucleoskeleton Binding Disrupt Nuclear Structure and Promote Breast Cancer Cell Motility and Metastasis.

Nuclear envelope proteins play an important role in regulating nuclear size and structure in cancer. Altered expression of nuclear lamins are found in many cancers and its expression is correlated with better clinical outcomes. The nucleus is the largest organelle in the cell with a diameter between 10 and 20 µm. Nuclear size significantly impacts cell migration. Nuclear structural changes are predicted to impact cancer metastasis by regulating cancer cell migration. Here we show emerin regulates nuclear structure in invasive breast cancer cells to impact cancer metastasis. Invasive breast cancer cells had 40% to 50% less emerin than control cells, which resulted in decreased nuclear size. Overexpression of GFP-emerin in invasive breast cancer cells rescued nuclear size and inhibited migration through 3.0 and 8.0 µm pores. Mutational analysis showed emerin binding to nucleoskeletal proteins was important for its regulation of nuclear structure, migration, and invasion. Importantly, emerin expression inhibited lung metastasis by 91% in orthotopic mouse models of breast cancer. Emerin nucleoskeleton-binding mutants failed to inhibit metastasis. These results support a model whereby emerin binding to the nucleoskeleton regulates nuclear structure to impact metastasis. In this model, emerin plays a central role in metastatic transformation, because decreased emerin expression during transformation causes the nuclear structural defects required for increased cell migration, intravasation, and extravasation. IMPLICATIONS: Modulating emerin expression and function represents new targets for therapeutic interventions of metastasis, because increased emerin expression rescued cancer metastasis.

CAPER as a therapeutic target for triple negative breast cancer.

Breast cancers (BCas) that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are referred to as triple negative breast cancers (TNBCs) and have the poorest clinical outcome. Once these aggressive tumors progress to distant organs, the median survival decreases to 12 months. With endocrine therapies being ineffective in this BCa subtype, highly toxic chemo- and radiation therapies are the only options. A better understanding of the functional role(s) of molecular targets contributing to TNBC progression could help in the design and development of new treatments that are more targeted with less toxicity. CAPER (Co-activator of AP-1 and ER) is a nuclear transcriptional co-activator that was recently involved in ER-positive BCa progression, however its role in hormone-independent cancers remains unknown. Our current report demonstrates that CAPER expression is upregulated in human TNBC specimens compared to normal breast tissue and that its selective downregulation through a lentiviral-mediated shRNA knockdown approach resulted in decreased cell numbers in MDA-MB-231 and BT549 TNBC cell lines without affecting the growth of non-tumorigenic cell line MCF-10A. Concordant with these observations, CAPER knockdown was also associated with a decrease in DNA repair proteins leading to a marked increase in apoptosis, through caspase-3/7 activation without any changes in cell cycle. Collectively, we propose CAPER as an important signaling molecule in the development of TNBC linked to DNA repair mechanisms, which could lead to new therapeutic modalities for the treatment of this aggressive cancer.

The effects of alcohol on responses to nicotine-containing and denicotinized cigarettes in dependent and nondaily smokers.

BACKGROUND: Alcohol consumption has been linked to increased tobacco use and craving in both dependent and nondaily smokers, yet the extent to which these relationships depend on interactions involving nicotine remains unclear. This study examined the acute effects of alcohol on the subjective and behavioral responses to nicotine-containing tobacco and denicotinized tobacco in 17 (10 male) dependent daily smokers (DDS) and 23 (11 male) nondependent nondaily smokers (NNS). METHODS: During 4 randomized double-blind sessions, participants assessed the effects of nicotine-containing tobacco or denicotinized tobacco following the administration of a moderately intoxicating dose of alcohol (mean blood alcohol concentration = 0.076 g/dl) or a placebo beverage. They could then self-administer additional puffs of the same type of cigarette sampled over a 60-minute period using a progressive ratio task. RESULTS: In NNS, alcohol significantly increased the self-administration of both nicotine-containing and denicotinized cigarettes, and no differences in self-administration were observed between the 2 types of tobacco within either beverage condition. In contrast, in DDS, alcohol was associated with decreased denicotinized tobacco self-administration relative to the placebo beverage condition as well as with increased self-administration of nicotine-containing tobacco relative to denicotinized tobacco. DDS also exhibited relatively elevated craving following the administration of a nicotine-containing cigarette in the alcohol beverage condition. CONCLUSIONS: Findings suggest that nicotine may be critical to the drinking-smoking relationship in DDS, but that nonnicotine smoking factors may be more important in NNS.

Alcohol and tobacco co-use in nondaily smokers: an inevitable phenomenon?

INTRODUCTION AND AIMS: Alcohol use has consistently been associated with smoking among nondaily smokers. However, this may not be an inevitable relationship that extends across all drinking sessions and/or all nondaily smokers. Recently, distinct subgroups of nondaily smokers have been identified, with one subgroup maintaining a stable pattern of nondaily smoking (long-term occasional smokers; LOS), and others transitioning to nondaily smoking either from a non-smoking status (early occasional smokers; EOS) or from a daily smoking status (former daily smokers; FDS). However, little is known about the extent to which these subgroups differ in their alcohol-tobacco co-administration patterns. DESIGN AND METHODS: 183 nondaily smokers (74 LOS; 55 EOS; 54 FDS) completed face-to-face interviews during which they provided details about their lifetime and past-week tobacco and alcohol administration patterns. RESULTS: EOS were more likely to report having used alcohol at the time of their first-ever cigarette relative to the other subgroups (P ≤ 0.001), but there were no differences in past-week co-administration patterns between the subgroups. Overall, less than one-third of all smoking sessions occurred when drinking, but these accounted for more than half of all cigarettes consumed during the previous week. Moreover, while only 42% of drinking sessions involved tobacco co-administration, when drinking and smoking did co-occur, significantly greater amounts of alcohol were consumed relative to drinking sessions where no tobacco was used (P < 0.01). DISCUSSION AND CONCLUSIONS: Findings suggest that alcohol use is not invariably related to smoking in EOS, FDS or LOS, but when it is, across all subgroups co-administration is associated with mutual dose escalation.

The acute effect of Swedish-style snus on cigarette craving and self-administration in male and female smokers.

INTRODUCTION: Swedish-style snus (SS) has recently garnered controversy for its proposed use as a smoking cessation aid and/or harm reduction tool. However, to date, little work has been done to evaluate the extent to which SS affects cigarette cravings and smoking behavior under double-blind controlled conditions. METHODS: During four double-blind placebo-controlled randomized sessions, 15 smokers (8 male) administered SS, placebo (nicotine/tobacco-free) snus (PS), a nicotine-containing lozenge (NL), or a placebo lozenge (PL) for 30 min and assessed their effects using Visual Analogue Scales and the Brief Questionnaire of Smoking Urges. They could then self-administer their usual brand of cigarettes using a progressive ratio task over the next 60 min. Following the completion of their final session, 11 participants (6 male) ranked each of the products used in the study in terms of their preferences. RESULTS: Relative to the other products, SS was associated with a decreased intention to smoke as well as a delayed onset of cigarette smoking in men but not women. However, SS administration was also associated with increased feelings of frustration and irritability relative to NL and SS was ranked as being the least preferred product used in the study. DISCUSSION: Findings suggest that SS is effective in acutely suppressing craving and smoking in at least some smokers, but that its acceptability may be limited.