Evaluation of Culture Conducive to Academic Success by Gender at a Comprehensive Cancer Center.

INTRODUCTION: The primary objective of this study was to determine whether workplace culture in academic oncology differed by gender, during the COVID-19 pandemic. MATERIALS AND METHODS: We used the Culture Conducive to Women's Academic Success (CCWAS), a validated survey tool, to investigate the academic climate at an NCI-designated Cancer Center. We adapted the CCWAS to be applicable to people of all genders. The full membership of the Cancer Center was surveyed (total faculty = 429). The questions in each of 4 CCWAS domains (equal access to opportunities, work-life balance, freedom from gender bias, and leadership support) were scored using a 5-point Likert scale. Median score and interquartile ranges for each domain were calculated. RESULTS: A total of 168 respondents (men = 58, women = 106, n = 4 not disclosed) submitted survey responses. The response rate was 39% overall and 70% among women faculty. We found significant differences in perceptions of workplace culture by gender, both in responses to individual questions and in the overall score in the following domains: equal access to opportunities, work-life balance, and leader support, and in the total score for the CCWAS. CONCLUSIONS: Our survey is the first of its kind completed during the COVID-19 pandemic at an NCI-designated Cancer Center, in which myriad factors contributed to burnout and workplace challenges. These results point to specific issues that detract from the success of women pursuing careers in academic oncology. Identifying these issues can be used to design and implement solutions to improve workforce culture, mitigate gender bias, and retain faculty.

Associations between the Gut Microbiota, Race, and Ethnicity of Patients with Colorectal Cancer: A Pilot and Feasibility Study.

BACKGROUND: Colorectal cancer (CRC) is more prevalent among some racial and ethnic minority and low socioeconomic status populations. Although the gut microbiota is a risk factor for CRC and varies with race and ethnicity, its role in CRC disparities remains poorly understood. METHODS: We examined the feasibility of recruiting sociodemographically diverse CRC patients for a microbiome study involving a home stool collection. We also explored whether race and ethnicity were associated with gut microbiome composition. We recruited Black/African American, Hispanic/Latino, and non-Hispanic White patients who were receiving care for active CRC to complete a comprehensive dietary and lifestyle survey, self-collect a stool sample, and complete an exit interview. Gut microbial diversity and composition were analyzed using 16S rRNA gene sequencing. RESULTS: 30 individuals consented (of 35 who were eligible and contacted) with 5 (17%) Black/African American, 11 (37%) Hispanic/Latino, and 14 (46%) non-Hispanic White. A total of 22 (73%) completed the dietary and lifestyle survey; 18 (63%) returned a stool sample. Even after controlling for socioeconomic, dietary, or treatment-related covariates, microbiome composition was associated with race and ethnicity. Fusobacteriota (a phylum associated with the development and progression of CRC) was significantly higher in the Black/African American group compared to others, and microbial diversity was higher in samples from non-Hispanic White individuals compared to Hispanic/Latino individuals. CONCLUSION: Our study shows that it is feasible to recruit and collect stool samples from diverse individuals with CRC and found significant associations in gut microbial structure with race and ethnicity.

Variety of Fruit and Vegetables and Alcohol Intake are Associated with Gut Microbial Species and Gene Abundance in Colorectal Cancer Survivors.

BACKGROUND: Adherence to the American Cancer Society (ACS) guidelines of avoiding obesity, maintaining physical activity, and consuming a diet rich in fruits, vegetables, and whole grains is associated with longer survival in colorectal cancer (CRC) survivors. Dietary components of the ACS guidelines may act in part by changing the microbiome, which is implicated in CRC outcomes. OBJECTIVES: We conducted a pilot cross-sectional study to explore associations between ACS guidelines and the gut microbiome. METHODS: Stool samples and questionnaires were collected from 28 CRC survivors at the University of California, San Francisco from 2019 to 2020. ACS scores were calculated based on validated questionnaires. Gut microbial community structure from 16S amplicons and gene/pathway abundances from metagenomics were tested for associations with the ACS score and its components using ANOVA and general linear models. RESULTS: The overall ACS score was not significantly associated with variations in the fecal microbiota. However, fruit and vegetable intake and alcohol intake accounted for 19% (P = 0.005) and 13% (P = 0.01) of variation in the microbiota, respectively. Fruit/vegetable consumption was associated with increased microbial diversity, increased Firmicutes, decreased Bacteroidota, and changes to multiple genes and metabolic pathways, including enriched pathways for amino acid and short-chain fatty acid biosynthesis and plant-associated sugar degradation. In contrast, alcohol consumption was positively associated with overall microbial diversity, negatively associated with Bacteroidota abundance, and associated with changes to multiple genes and metabolic pathways. The other components of the ACS score were not statistically significantly associated with the fecal microbiota in our sample. CONCLUSIONS: These results guide future studies examining the impact of changes in the intake of fruits, vegetables, and alcoholic drinks on the gut microbiome of CRC survivors.

Association between adherence to the American Cancer Society Nutrition and Physical Activity Guidelines and stool frequency among colon cancer survivors: a cohort study.

PURPOSE: We sought to determine whether adherence to the American Cancer Society (ACS) Nutrition and Physical Activity Guidelines was associated with better bowel function among colon cancer survivors. METHODS: This prospective cohort study included patients surgically treated for stage I-IV colon cancer enrolled in the Lifestyle and Outcomes after Gastrointestinal Cancer (LOGIC) study between February 2017 and May 2021. Participants were assigned an ACS score (0-6 points) at enrollment. Stool frequency (SF) was assessed every 6 months using the EORTC QLQ-CR29. Higher SF is an indication of bowel function impairment. ACS score at enrollment was examined in relation to SF at enrollment and over a 3-year period. Secondarily, we examined associations between the ACS score components (body mass index, dietary factors, and physical activity) and SF. Multivariable models were adjusted for demographic and surgical characteristics. RESULTS: A total of 112 people with colon cancer (59% women, mean age 59.5 years) were included. Cross-sectionally, for every point increase in ACS score at enrollment, the odds of having frequent stools at enrollment decreased by 43% (CI 0.42-0.79; p < 0.01). Findings were similar when we examined SF as an ordinal variable and change in SF over a 3-year period. Lower consumption of red/processed meats and consuming a higher number of unique fruits and vegetables were associated with lower SF (better bowel function) at enrollment. CONCLUSIONS: Colon cancer survivors who more closely followed the ACS nutrition and physical activity guidelines had lower SF, an indication of better bowel function. IMPLICATIONS FOR CANCER SURVIVORS: Our findings highlight the value of interventions that support health behavior modification as part of survivorship care for long-term colon cancer survivors.

Optimizing intervention tools to improve nutrition and physical activity for colorectal cancer survivors (Tools To Be Fit): Study protocol of a randomized factorial experiment.

BACKGROUND: Colorectal cancer (CRC) is the 2nd leading cause of cancer death in the United States. The American Cancer Society (ACS) Nutrition and Physical Activity Guidelines are associated with longer survival among CRC survivors, but few report behaviors consistent with the guidelines. METHODS: The Tools To Be Fit study, based on the Multiphase Optimization Strategy (MOST) framework, is a full factorial experimental to optimize a remotely delivered 48-week diet and physical activity intervention for non-metastatic CRC survivors. The intervention includes a core component (booklet and personal report). CRC survivors (N = 400) are additionally randomly assigned to one of 16 combinations of four candidate components, each with 2 options: 1) text messaging (on/off); 2) self-monitoring modality (digital/paper); 3) health coaching (on/off); and 4) support person coaching (on/off). OUTCOMES: Our primary outcome is adherence to the ACS guidelines after 48 weeks using a score that includes physical activity from accelerometers, dietary intake from a food frequency questionnaire, and body mass index (BMI) measured by a technician. Secondary outcomes include the ACS score after 24 weeks and score components at 24 and 48 weeks. Exploratory outcomes include adherence and change in Social Cognitive Theory constructs. We will explore moderation by sociodemographic, clinical, and psychological/behavioral factors; and change in the ACS score in relation to change in levels of insulin, insulin sensitivity, inflammation, gut microbiome structure, fatigue, depression, and sleep disturbance. DISCUSSION: The proposed study aims to inform a randomized controlled trial to determine whether an optimized intervention reduces risk of recurrence among CRC survivors.

The Gut Microbiome in Colorectal Cancer.

The gut microbiome is important in human health and disease. Recent studies have begun to elucidate its specific role in colorectal cancer. The gut microbiome seems to play an integral role in colorectal cancer initiation and progression, and oncologic drug metabolism and toxicity. This review examines the associations between the gut microbiome and colorectal cancer initiation, progression, and oncologic drug metabolism, highlighting proposed mechanisms and landmark publications in this field. It also discusses potential methods of modulating the gut microbiome, underscoring the gaps in current understanding, and ends with a clinically relevant overview of microbiome research considerations and study design.

Feasibility and Acceptability of a Physical Activity Tracker and Text Messages to Promote Physical Activity During Chemotherapy for Colorectal Cancer: Pilot Randomized Controlled Trial (Smart Pace II).

BACKGROUND: We conducted a pilot 2-arm randomized controlled trial to assess the feasibility of a digital health intervention to increase moderate-to-vigorous physical activity in patients with colorectal cancer (CRC) during chemotherapy. OBJECTIVE: This study aimed to determine whether a digital health physical activity intervention is feasible and acceptable during chemotherapy for CRC. METHODS: Potentially eligible patients with CRC expected to receive at least 12 weeks of chemotherapy were identified in person at the University of California, San Francisco, and on the web through advertising. Eligible patients were randomized 1:1 to a 12-week intervention (Fitbit Flex, automated SMS text messages) versus usual care. At 0 and 12 weeks, patients wore an Actigraph GT3X+ accelerometer for 7 days and completed surveys, body size measurements, and an optional 6-minute walk test. Participants could not be masked to their intervention arm, but people assessing the body size and 6-minute walk test outcomes were masked. The primary outcomes were adherence (eg, Fitbit wear and text response rate) and self-assessed acceptability of the intervention. The intervention would be considered feasible if we observed at least 80% complete follow-up and 70% adherence and satisfaction, a priori. RESULTS: From 2018 to 2020, we screened 240 patients; 53.3% (128/240) of patients were ineligible and 26.7% (64/240) declined to participate. A total of 44 patients (44/240, 18%) were randomized to the intervention (n=22) or control (n=22) groups. Of these, 57% (25/44) were women; 68% (30/44) identified as White and 25% (11/44) identified as Asian American or Pacific Islander; and 77% (34/44) had a 4-year college degree. The median age at enrollment was 54 years (IQR 45-62 years). Follow-up at 12 weeks was 91% (40/44) complete. In the intervention arm, patients wore Fitbit devices on a median of 67 out of 84 (80%) study days and responded to a median of 17 out of 27 (63%) questions sent via SMS text message. Among 19 out of 22 (86%) intervention patients who completed the feedback survey, 89% (17/19) were satisfied with the Fitbit device; 63% (12/19) were satisfied with the SMS text messages; 68% (13/19) said the SMS text messages motivated them to exercise; 74% (14/19) said the frequency of SMS text messages (1-3 days) was ideal; and 79% (15/19) said that receiving SMS text messages in the morning and evening was ideal. CONCLUSIONS: This pilot study demonstrated that many people receiving chemotherapy for CRC are interested in participating in digital health physical activity interventions. Fitbit adherence was high; however, participants indicated a desire for more tailored SMS text message content. Studies with more socioeconomically diverse patients with CRC are required. TRIAL REGISTRATION: ClinicalTrials.gov NCT03524716; https://clinicaltrials.gov/ct2/show/NCT03524716.

Survival in Young-Onset Metastatic Colorectal Cancer: Findings From Cancer and Leukemia Group B (Alliance)/SWOG 80405.

BACKGROUND: The incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC). METHODS: We studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided. RESULTS: Of 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93). CONCLUSION: In this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older.

Resident-Reported Impact of a Novel Oncology Curriculum for Internal Medicine Residents.

The Accreditation Council of Graduate Medical Education mandates that all internal medicine residents gain exposure to internal medicine subspecialties including hematology and oncology. While many residents meet this criterion through inpatient oncology rotations, the current structure of many inpatient oncology rotations leaves little opportunity for formal education. We therefore designed a novel oncology curriculum consisting of one-page oncology teaching sheets to increase the number, breadth, and quality of formal teaching sessions on our resident inpatient oncology services. In order to evaluate the curriculum, we conducted pre- and post-intervention surveys of residents. From these surveys, we found that 72.2% of residents used the teaching sheets on their inpatient oncology rotation and that the teaching sheets led to an increase in the number of formal oncology teaching sessions (mean 3.4 ± 2.1 post-implementation vs 2.6 ± 2.0 pre-implementation, p = 0.008), the breadth of oncology topics taught (% reporting ≥ 5 topics; 26.1% vs 16.3%, p = 0.035), the proportion of residents reporting improvement in overall oncology knowledge (80.2% vs 62.4%, p = 0.012), and the proportion of residents reporting improvement in their ability to care for patients (70.8% vs 48.9%, p = 0.013). These results demonstrate that formal oncology teaching can be improved on inpatient oncology rotations through a simple and easily replicable oncology curriculum.

Primary osteosarcoma of the parietal bone.

Osteosarcoma is the most common primary bone tumor and usually involves the long bones. Osteosarcoma of the skull, on the other hand, is relatively rare. Here, we present a 29-year-old man with a growing mass in the skull he first noticed after a fall while skateboarding. The initial clinical diagnosis was hematoma. While undergoing an evacuation surgery for a hematoma, a suspicious mass was detected which was biopsied. Histopathological evaluation showed high-grade osteosarcoma. The patient was referred to our hospital where he underwent definitive resection followed by adjuvant chemotherapy. His course was complicated by wound infection. Even though osteosarcoma of the skull is a rare finding, it should be suspected in a patient with a skull mass, and the history of prior head trauma does not exclude the diagnosis.

Cancer health disparities in racial/ethnic minorities in the United States.

There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA-African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.

Guidelines for Evaluating the Feasibility of Recruitment in Pilot Studies of Diverse Populations: An Overlooked but Important Component.

Background: In health disparities research, studies often fall short of their recruitment goals. Conducting a pilot feasibility study of recruitment in which data are collected systematically on recruitment processes can help investigators refine methods for the larger study. However, there are few guidelines for conducting pilot feasibility studies, and recruitment methods are seldom the focus. Feasibility indicators differ from traditional reports of recruitment results by focusing on the extent to which recruitment goals are met. Methods: We present an organizing framework for assessing the feasibility of recruitment that includes eight steps, briefly: 1) specify recruitment goals; 2) specify recruitment processes; 3) establish a tracking system for each individual; 4) establish a tracking database for monitoring processes and results; 5) implement recruitment and track each individual's progress; 6) summarize recruitment results; 7) calculate and interpret feasibility measures - were goals met; and 8) if goals were not met, utilize tracking data to modify methods for the larger study. We describe methods within each step, with added details for steps 2-5 (the specific processes). The framework draws from a small literature on recruitment feasibility with a focus on health disparities populations. The guidelines blend well-known methods of recruitment with additional information on calculating feasibility indicators. Conclusions: These guidelines provide a first step in thinking systematically about recruitment feasibility, to advance the field of measuring feasibility. Feasibility indicators also can be used to track the effectiveness of innovative recruitment strategies as part of building the science of recruitment, especially in disparities populations.

Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer.

Despite recent advances in the management of colorectal cancer, metastatic disease remains challenging, and patients are rarely cured. However, a better understanding of the pathways implicated in the evolution and proliferation of cancer cells has led to the development of targeted therapies, that is, agents with action directed at these pathways/features. This approach is more specific to cells within which these pathways, such as epidermal growth factor receptor (EGFR), are overactive; this is in contrast to the relatively indiscriminate mechanism by which cytotoxic chemotherapy tends to affect rapidly dividing cells, regardless of their role. Although factors unique to a given patient, such as the location of the primary tumor (sidedness) or the presence of mutations that confer resistance, may limit the utility of these agents, targeted therapies are now a part of the treatment paradigm for metastatic colorectal cancer, and survival outcomes have significantly improved. This review provides an overview of the role of targeted therapy in the management of patients with colorectal cancer metastases as well as a discussion of issues in patient selection, with a focus on inhibitors of angiogenesis, EGFR-targeted therapy, BRAF mutation-targeted therapies, and other novel strategies, including immunotherapy.

A case report of vanishing bile duct syndrome after exposure to pexidartinib (PLX3397) and paclitaxel.

Pexidartinib (PLX3397) is a small molecule tyrosine kinase and colony-stimulating factor-1 inhibitor with FDA breakthrough therapy designation for tenosynovial giant-cell tumor, and currently under study in several other tumor types, including breast cancer, non-Hodgkin's lymphoma, and glioblastoma. Here, we report a case of severe drug-induced liver injury requiring liver transplantation due to vanishing bile duct syndrome (VBDS) after exposure to pexidartinib in the I-SPY 2 Trial, a phase 2 multicenter randomized neoadjuvant chemotherapy trial in patients with Stage II-III breast cancer. We also review the current literature on this rare, idiosyncratic, and potentially life-threatening entity.

What is the Role of the Arts in Medical Education and Patient Care? A Survey-based Qualitative Study.

To inform medical education reform efforts, we systematically collected information on the level of arts and humanities engagement in our medical school community. Attitudes regarding incorporating arts and humanities-based teaching methods into medical education and patient care were also assessed. An IRB-approved survey was electronically distributed to all faculty, residents, fellows, and students at our medical school. Questions focused on personal practice of the arts and/or humanities, as well as perceptions of, and experience with formally incorporating these into medical teaching. Of 13,512 community members surveyed, 2,775 responded (21% overall response rate). A majority of respondents agreed or strongly agreed that medical education and patient care could be "enhanced" by the integration of the arts (67% and 74% respectively). There was enthusiastic support for the creation of a formal program in the arts at our medical school (72 %). Integration of the arts into medical education may have a role in improving the quality of medical training and would likely be well received by teachers and learners.

A Prospective Study of Alcohol Consumption and Smoking and the Risk of Major Gastrointestinal Bleeding in Men.

BACKGROUND AND AIMS: Data regarding smoking and alcohol consumption and risk of gastrointestinal bleeding (GIB) are sparse and conflicting. We assessed the risk of major GIB associated with smoking and alcohol consumption in a large, prospective cohort. METHODS: We prospectively studied 48,000 men in the Health Professional follow-up Study (HPFS) who were aged 40-75 years at baseline in 1986. We identified men with major GIB requiring hospitalization and/or blood transfusion via biennial questionnaires and chart review. RESULTS: We documented 305 episodes of major GIB during 26 years of follow-up. Men who consumed >30 g/day of alcohol had a multivariable relative risk (RR) of 1.43 (95% confidence interval (CI), 0.88-2.35; P for trend 0.006) for major GIB when compared with nondrinkers. Alcohol consumption appeared to be primarily related to upper GIB (multivariable RR for >30 g/day vs. nondrinkers was 1.35; 95% CI, 0.66-2.77; P for trend 0.02). Men who consumed ≥ 5 drinks/week vs. < 1 drink/month of liquor had a multivariable RR of 1.72 (95% CI, 1.26-2.35, P for trend <0.001). Wine and beer were not significantly associated with major GIB. The risk of GIB associated with NSAIDs/aspirin use increased with greater alcohol consumption (multivariable RR 1.37; 95% CI, 0.85-2.19 for 1-14g/day of alcohol, RR 1.75; 95% CI, 1.07-2.88 for ≥ 15g/day compared to nondrinkers). Smoking was not significantly associated with GIB. CONCLUSIONS: Alcohol consumption, but not smoking, was associated with an increased risk of major GIB. Associations were most notable for upper GIB associated with liquor intake. Alcohol appeared to potentiate the risk of NSAID-associated GIB.

Patient navigation to improve follow-up of abnormal mammograms among disadvantaged women.

BACKGROUND: Patient navigation (PN) can improve breast cancer care among disadvantaged women. We evaluated the impact of a PN program on follow-up after an abnormal mammogram. METHODS: Between 2007 and 2010, disadvantaged women with an abnormal mammogram (Breast Imaging-Reporting and Data System [BI-RADS] codes 0, 3, 4, 5) cared for in a community health center (CHC) with PN were compared to those receiving care in 11 network practices without PN. Multivariable logistic regression and Cox proportional hazards modeling were used to compare the percentages receiving appropriate follow-up and time to follow-up between the groups. RESULTS: Abnormal mammography findings were reported for 132 women in the CHC with PN and 168 from practices without PN. The percentage of women with appropriate follow-up care was higher in the practice with PN than in non-PN practices (90.4% vs. 75.3%, adjusted p=0.006). RESULTS varied by BI-RADS score for women in PN and non-PN practices (BI-RADS 0, 93.7% vs. 90.2%, p=0.24; BI-RADS 3, 85.7% vs. 49.2%, p=0.003; BI-RADS 4/5, 95.1% vs. 82.8%, p=0.26). Time to follow-up was similar for BI-RADS 0 and occurred sooner for women in the PN practice than in non-PN practices for BI-RADS 3 and 4/5 (BI-RADS 3, adjusted hazard ratio [aHR], 95% confidence interval [CI]: 2.41 [1.36-4.27], BI-RADS 4/5, aHR [95% CI]: 1.41 [0.88-2.24]). CONCLUSIONS: Disadvantaged women from a CHC with PN were more likely to receive appropriate follow-up after an abnormal mammogram than were those from practices without PN. Expanding PN to include all disadvantaged women within primary care networks could improve equity in cancer care.

CASK deletion in intestinal epithelia causes mislocalization of LIN7C and the DLG1/Scrib polarity complex without affecting cell polarity.

CASK is the mammalian ortholog of LIN2, a component of the LIN2/7/10 protein complex that targets epidermal growth factor receptor (EGFR) to basolateral membranes in Caenorhabditis elegans. A member of the MAGUK family of scaffolding proteins, CASK resides at basolateral membranes in polarized epithelia. Its interaction with LIN7 is evolutionarily conserved. In addition, CASK forms a complex with another MAGUK, the DLG1 tumor suppressor. Although complete knockout of CASK is lethal, the gene is X-linked, enabling us to generate heterozygous female adults that are mosaic for its expression. We also generated intestine-specific CASK knockout mice. Immunofluorescence analysis revealed that in intestine, CASK is not required for epithelial polarity or differentiation but is necessary for the basolateral localization of DLG1 and LIN7C. However, the subcellular distributions of DLG1 and LIN7C are independent of CASK in the stomach. Moreover, CASK and LIN7C show normal localization in dlg1(-/-) intestine. Despite the disappearance of basolateral LIN7C in CASK-deficient intestinal crypts, this epithelium retains normal localization of LIN7A/B, EGFR and ErbB-2. Finally, crypt-to-villus migration rates are unchanged in CASK-deficient intestinal epithelium. Thus, CASK expression and the appropriate localization of DLG1 are not essential for either epithelial polarity or intestinal homeostasis in vivo.