Patient and Caregiver Perceptions of an Interface Design to Communicate Artificial Intelligence-Based Prognosis for Patients With Advanced Solid Tumors.

PURPOSE: Use of artificial intelligence (AI) in cancer care is increasing. What remains unclear is how best to design patient-facing systems that communicate AI output. With oncologist input, we designed an interface that presents patient-specific, machine learning-based 6-month survival prognosis information designed to aid oncology providers in preparing for and discussing prognosis with patients with advanced solid tumors and their caregivers. The primary purpose of this study was to assess patient and caregiver perceptions and identify enhancements of the interface for communicating 6-month survival and other prognosis information when making treatment decisions concerning anticancer and supportive therapy. METHODS: This qualitative study included interviews and focus groups conducted between November and December 2022. Purposive sampling was used to recruit former patients with cancer and/or former caregivers of patients with cancer who had participated in cancer treatment decisions from Utah or elsewhere in the United States. Categories and themes related to perceptions of the interface were identified. RESULTS: We received feedback from 20 participants during eight individual interviews and two focus groups, including four cancer survivors, 13 caregivers, and three representing both. Overall, most participants expressed positive perceptions about the tool and identified its value for supporting decision making, feeling less alone, and supporting communication among oncologists, patients, and their caregivers. Participants identified areas for improvement and implementation considerations, particularly that oncologists should share the tool and guide discussions about prognosis with patients who want to receive the information. CONCLUSION: This study revealed important patient and caregiver perceptions of and enhancements for the proposed interface. Originally designed with input from oncology providers, patient and caregiver participants identified additional interface design recommendations and implementation considerations to support communication about prognosis.

ATA risk stratification in papillary thyroid microcarcinoma has low positive predictive value when identifying recurrence.

BACKGROUND: Rising incidence of papillary thyroid microcarcinomas (PTMC) has raised concerns for overdiagnosis. Utility of the American Thyroid Association Risk Stratification System (ATA-RSS) 2015 in predicting risk of disease recurrence in patients with PTMC was assessed. METHODS: Electronic health records of patients who underwent total thyroidectomy were queried. ATA-RSS 2015 risk stratification was performed on those with PTMC, and validity for predicting disease recurrence was calculated. RESULTS: With 10-year median follow up, recurrence was higher in PTMC patients with high/intermediate vs low ATA risk (33 â€‹% vs 4 â€‹%, p â€‹= â€‹0.002). Sensitivity of ATA-RSS for detecting recurrence was 60 â€‹%, specificity 90 â€‹%, PPV 33.3 â€‹%, NPV 96.6 â€‹%, and accuracy 88 â€‹%. When microscopic extrathyroidal extension (ETE) was excluded as an intermediate risk criterion, PPV improved to 50 â€‹% and accuracy improved to 92.5 â€‹% CONCLUSIONS: ATA-RSS 2015 predicts recurrence in PTMC with high NPV but low PPV. Exclusion of microscopic ETE improved PPV, which may help prevent overtreatment.

Design of an interface to communicate artificial intelligence-based prognosis for patients with advanced solid tumors: a user-centered approach.

OBJECTIVES: To design an interface to support communication of machine learning (ML)-based prognosis for patients with advanced solid tumors, incorporating oncologists' needs and feedback throughout design. MATERIALS AND METHODS: Using an interdisciplinary user-centered design approach, we performed 5 rounds of iterative design to refine an interface, involving expert review based on usability heuristics, input from a color-blind adult, and 13 individual semi-structured interviews with oncologists. Individual interviews included patient vignettes and a series of interfaces populated with representative patient data and predicted survival for each treatment decision point when a new line of therapy (LoT) was being considered. Ongoing feedback informed design decisions, and directed qualitative content analysis of interview transcripts was used to evaluate usability and identify enhancement requirements. RESULTS: Design processes resulted in an interface with 7 sections, each addressing user-focused questions, supporting oncologists to "tell a story" as they discuss prognosis during a clinical encounter. The iteratively enhanced interface both triggered and reflected design decisions relevant when attempting to communicate ML-based prognosis, and exposed misassumptions. Clinicians requested enhancements that emphasized interpretability over explainability. Qualitative findings confirmed that previously identified issues were resolved and clarified necessary enhancements (eg, use months not days) and concerns about usability and trust (eg, address LoT received elsewhere). Appropriate use should be in the context of a conversation with an oncologist. CONCLUSION: User-centered design, ongoing clinical input, and a visualization to communicate ML-related outcomes are important elements for designing any decision support tool enabled by artificial intelligence, particularly when communicating prognosis risk.

Caregiver Burden and Workplace Productivity Among Hospice Cancer Caregivers.

OBJECTIVES: To examine the relationships among family caregiver burden and workplace productivity and activity impairment among home hospice family caregivers of individuals with cancer who worked while providing end-of-life caregiving. SAMPLE & SETTING: Baseline data from a longitudinal study of communication between hospice providers and hospice family caregivers were used for this secondary analysis. METHODS & VARIABLES: Working family caregivers with complete workplace productivity and activity impairment data were included in this analysis (N = 30). Demographic data, caregiver burden, and workplace productivity and activity impairment were examined with descriptive statistics, correlation analysis, and hierarchical linear regressions. RESULTS: Hospice family caregivers were primarily White, female, married, and employed full-time. Caregiver burden levels were significantly positively associated with activity impairment, presenteeism, and work productivity loss. These relationships remained statistically significant when controlling for age. IMPLICATIONS FOR NURSING: Hospice and oncology nurses can support working hospice family caregivers by assessing for burden and associated workplace challenges, as well as by providing referrals for respite and community resources.

Does Non-Classic Lobular Carcinoma In Situ at the Lumpectomy Margin Increase Local Recurrence?

BACKGROUND: The clinical significance of nonclassic, lobular carcinoma in situ (NC-LCIS) at the surgical margin of excisions for invasive cancer is unknown. We sought to determine whether NC-LCIS at or near the margin in the setting of a concurrent invasive carcinoma is associated with risk of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR). METHODS: Patients with stage 0-III breast cancer and NC-LCIS who underwent lumpectomy between January 2010 and January 2022 at a single institution were retrospectively identified. NC-LCIS margins were stratified as <2 mm, ≥2 mm, or within shave margin. Rates of IBTR and LRR were examined. RESULTS: A total of 511 female patients (median age 60 years [interquartile range (IQR) 52-69]) with NC-LCIS and an associated ipsilateral breast cancer with a median follow-up of 3.4 years (IQR 2.0-5.9) were identified. Final margins for NC-LCIS were ≥2 mm in 348 patients (68%), <2 mm in 37 (7.2%), and within shave margin in 126 (24.6%). Crude incidence of IBTR was 3.3% (n = 17) and that of LRR was 4.9% (n = 25). There was no difference in the crude rate of IBTR by NC-LCIS margin status (IBTR rate: 3.7% ≥2 mm, 0% <2 mm, 3.2% within shave margin, p = 0.8) nor in LRR (LRR rate: 4.9% ≥2 mm, 2.7% <2 mm, 5.6% within shave margin, p = 0.9). CONCLUSIONS: For completely excised invasive breast cancers associated with NC-LCIS, extent of margin width for NC-LCIS was not associated with a difference in IBTR or LRR. These data suggest that the decision to perform reexcision of margin after lumpectomy should be driven by the invasive cancer, rather than the NC-LCIS margin.

Axillary lymph node dissection: Dead or still alive?

Although sentinel lymph node biopsy is now the primary method of axillary staging and is therapeutic for patients with limited nodal disease, axillary lymph node dissection (ALND) is still necessary for staging in groups where sentinel lymph node biopsy has not been proven to be accurate and to maintain local control in those with a heavy axillary tumor burden. Additionally, newer approaches to systemic therapy tailored to risk level sometimes necessitate knowledge of the number of involved axillary nodes which can only be obtained with ALND. Ongoing trials will address whether there are additional circumstances where radiotherapy can replace ALND.

A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology.

Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank of human patient-derived xenografts (PDXs) and matched organoid cultures from tumors that represent the greatest unmet need: endocrine-resistant, treatment-refractory and metastatic breast cancers. We leverage matched PDXs and PDX-derived organoids (PDxO) for drug screening that is feasible and cost-effective with in vivo validation. Moreover, we demonstrate the feasibility of using these models for precision oncology in real time with clinical care in a case of triple-negative breast cancer (TNBC) with early metastatic recurrence. Our results uncovered a Food and Drug Administration (FDA)-approved drug with high efficacy against the models. Treatment with this therapy resulted in a complete response for the individual and a progression-free survival (PFS) period more than three times longer than their previous therapies. This work provides valuable methods and resources for functional precision medicine and drug development for human breast cancer.

Preoperative Advance Care Planning for Older Adults Undergoing Major Abdominal Surgery.

BACKGROUND: Advance care planning (ACP) is recommended for older patients undergoing surgery. ACP consists of creating advance directives (ADs), identifying surrogate decision makers (SDMs), and documenting goals of care. We identified factors associated with documentation of preoperative ACP to identify opportunities to optimize ACP for older surgical patients. METHODS: This was a retrospective study of surgical patients ≥70 years old who underwent elective, high-risk abdominal procedures between 01/2015-08/2019. Clinical data were obtained from our institution's National Surgical Quality Improvement Project database. ACP metrics were extracted from the electronic medical record. We analyzed the data to identify patient factors associated with ACP metrics. We also analyzed whether ACP was more frequent for patients who experienced postoperative complications or death. RESULTS: 267/1,651 patients were included. 97 patients (36%) had an AD available on the day of surgery, 57 (21%) had an SDM identified, and 31 (12%) had a documented goals of care conversation. On multivariable analysis, older age and white race were associated with an increased likelihood of having an AD available on the day of surgery. Women were 1.7 times more likely to have an SDM (p = 0.02). No patient or surgeon factors were significantly associated with goals of care documentation. ACP was not performed more frequently in patients who experienced postoperative complications or death. CONCLUSION: In this series, ACP was not routinely documented for older patients undergoing major surgery. ACP was not more frequent in patients who experienced complications or death, demonstrating the importance of universal preoperative ACP in older patients.

Influence of endocrine multidisciplinary tumor board on patient management and treatment decision making.

BACKGROUND: Multidisciplinary Tumor Boards (MDT) are used to obtain input regarding cancer management. This study assessed the impact of our institutional Endocrine MDT. METHODS: MDT notes on patients with thyroid cancer treated during 2012-2018 were abstracted retrospectively from the electronic medical record. Management change (MC) was prospectively collected by the MDT coordinator. Biannual evaluations reviewed the impact of the MDT as observed by attendees. RESULTS: MC was recommended in 47 (15%) of 286 presentations, with additional imaging being the most frequent (43%). Presentation of recurrences were more likely to result in MC (24% vs. 13% initial, p = 0.03). Overall, 98% of attendees found the conference exceeded educational expectations. About 24% reported intending to use a more evidence/guideline-based approach after attending and this trend increased over time (p = 0.002). CONCLUSION: MDT presentations led to a higher rate of MC particularly in recurrent TC patients and increased evidenced-based practice for attendees.

Risk management recommendations and patient acceptance vary with high-risk breast lesions.

INTRODUCTION: Lobular carcinoma in situ (LCIS), atypical ductal and lobular hyperplasia (AH) increase breast cancer risk. We examined risk management recommendations (RMR) and acceptance in AH/LCIS. METHODS: All patients with AH/LCIS on core needle biopsy from 2013 to 2016 at our institution were identified; cancer patients were excluded. Univariate and multivariate analysis examined factors associated with management. RESULTS: 98 % of patients were evaluated by breast surgeons and 53 % underwent risk model calculation (RC). 77 % had new RMR. RMR of MRI screening (MRI), genetic counselling (GC) and medical oncology (MO) referral were 41 %, 18 %, 77 %, respectively. MRI screening was more likely recommended in those with strong family history (p = 0.01), and high RC (p < 0.001). Uptake of at least one RMR did not occur in 84 % of patients. Use of RC correlated with MO acceptance (p = 0.049). CONCLUSIONS: Diagnosis of atypia has the potential to change risk management for most, however only 16 % of patients accepted all RMR.

Expression of cancer stem cell markers in tall cell variant papillary thyroid cancer identifies a molecular profile predictive of recurrence in classic papillary thyroid cancer.

BACKGROUND: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. METHODS: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. RESULTS: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). CONCLUSION: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.

What contextual factors account for anxiety and depressed mood in hospice family caregivers?

OBJECTIVE: End-of-life caregiving is associated with poorer mental health compared with other caregiving. The objective of this study was to examine the association between contextual characteristics and appraisal factors on family caregivers' mental health and well-being. METHODS: Family hospice caregivers were recruited across four states using a non-probabilistic sampling approach. This study analyzed contextual (demographic, caregiving, economic) and appraisal factors (Medical Outcomes Study Social Support Survey, Zarit Burden Interview) on caregivers' anxiety and depression (Hospital Anxiety and Depression scale, and positive affect and well-being (Positive Affect and Well-being Scale). Hierarchical linear regression models were generated in SPSS version 24. RESULTS: Data from 102 family caregivers were analyzed. On average, participants were 58.93 years of age (SD = 14.24), mostly female (72.55%), spouses/partners (51.96%), and non-Hispanic White (78.43%). Most (75.49%) described their financial situation as comfortable or more than adequate. Younger age (B = -0.11, 95% CI = -0.18 to -0.05) and increased caregiving burden (B = 0.18, 95% CI = 0.09 to 0.27) were associated with increased anxiety, while lower perceived financial adequacy (B = -1.19, 95% CI = -2.07 to -0.32), lower social support (B = -0.04, 95% CI = -0.06 to -0.01), and increased caregiving burden (B = 0.15, 95% CI = 0.08-0.22) were associated with worsened depression. Greater social support (B = 0.10, 95% CI = 0.05-0.14) and lower caregiving burden (B = -0.19, 95% CI = -0.32 to -0.07) were associated with greater positive affect and well-being. CONCLUSIONS: Findings suggest significant impact of contextual factors on mental health and well-being, and support the need for holistic assessment of hospice caregivers' wellbeing and programs and policies providing social services and economic support to caregivers.

Patterns of stress and support in social support networks of in-home hospice cancer family caregivers.

Family caregivers of home hospice cancer patients often experience burden and distress, which can be mitigated by perceived social support. However, less attention has been paid to the non-family sources of support within social networks, or to how sources of support may also be sources of stress. We describe support and stress in social networks of hospice family caregivers and identify caregiving characteristics associated with classes identified in our data. We collected demographic and psychosocial self-report data from family caregivers providing in-home hospice care for advanced cancer patients (N = 90). Caregivers also reported perceived support and stress from specific family and non-family relationships. We identified three classes with unique patterns of stress and support within caregivers' support networks using a latent class analysis. Classes include: 1) high support, low stress across family and non-family network members ("supportive"; 53% of caregivers); 2) high support, high stress across family and non-family network ("ambivalent maximizers"; 26%); and 3) high support, high stress across family network only ("family-focused ambivalent"; 21%). Caregivers in the ambivalent maximizer class reported more burden than caregivers in the supportive class (p = .024). This is one of the first studies to systematically explore the role of non-family support, as well as how stress and support co-occur within relationships and across networks. As informal support networks of hospice family caregivers are complex and multifaceted, understanding the patterns of support and stress across various network members is essential to offer services to more effectively manage caregiver burden.

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.

AP-2α-Mediated Activation of E2F and EZH2 Drives Melanoma Metastasis.

In melanoma metastasis, the role of the AP-2α transcription factor, which is encoded by TFAP2A, is controversial as some findings have suggested tumor suppressor activity while other studies have shown high TFAP2A expression in node-positive melanoma associated with poor prognosis. Here we demonstrate that AP-2α facilitates melanoma metastasis through transcriptional activation of genes within the E2F pathway including EZH2. A BioID screen found that AP-2α interacts with members of the nucleosome remodeling and deacetylase (NuRD) complex. Loss of AP-2α removed activating chromatin marks in the promoters of EZH2 and other E2F target genes through activation of the NuRD repression complex. In melanoma cells, treatment with tazemetostat, an FDA-approved and highly specific EZH2 inhibitor, substantially reduced anchorage-independent colony formation and demonstrated heritable antimetastatic effects, which were dependent on AP-2α. Single-cell RNA sequencing analysis of a metastatic melanoma mouse model revealed hyperexpansion of Tfap2a High/E2F-activated cell populations in transformed melanoma relative to progenitor melanocyte stem cells. These findings demonstrate that melanoma metastasis is driven by the AP-2α/EZH2 pathway and suggest that AP-2α expression can be used as a biomarker to predict responsiveness to EZH2 inhibitors for the treatment of advanced melanomas. SIGNIFICANCE: AP-2α drives melanoma metastasis by upregulating E2F pathway genes including EZH2 through inhibition of the NuRD repression complex, serving as a biomarker to predict responsiveness to EZH2 inhibitors.

A Pilot Study of Preoperative Vandetanib on Markers of Proliferation and Apoptosis in Breast Cancer.

INTRODUCTION: Preclinical data supports antitumor activity of tyrosine kinase inhibitor vandetanib with Ret as the therapeutic target in breast cancer. We investigated the effect of preoperative vandetanib on markers of proliferation and apoptosis in breast cancer. METHODS: Patients with invasive breast cancer were randomly assigned vandetanib 300 mg or placebo PO daily for 2 weeks before operative resection from January 2014 to June 2017. Pretreatment and posttreatment specimens were analyzed by immunohistochemistry for Ki-67, TUNEL, and p-ERK with stratification by Ret expression by immunohistochemistry. RESULTS: Ten patients were enrolled. There was no statistically significant difference in ERK activation compared with placebo (P=0.45); however, ERK activation was reduced 74% compared with pretreatment biopsy with vandetinib treatment (P=0.005) without a significant reduction in the placebo group (-29%, P=0.55). Mean change in Ki-67 after vandetanib treatment was +0.3% compared with +2.0% in placebo treated patients, P=0.72. Mean change in TUNEL was +0.48 apoptotic nuclei per HPF in the vandetanib arm compared with +1.02 in the placebo arm, P=0.32. In vandetanib treated patients, Ki-67 was reduced 0.3% in RET-positive tumors compared with increased 1.0% in RET-negative tumors, P=0.43 and TUNEL was increased 0.77 in RET-positive tumors and 0.2 in RET-negative tumors, P=0.21. CONCLUSIONS: In this pilot study, no statistically significant differences on prespecified markers were seen with vandetanib compared with placebo. In accordance with the investigational hypothesis, there was a nonsignificant trend with vandetanib treatment of reduction in p-ERK and increased effects in Ret expressing tumors.

Evaluation of Oncology Hospital at Home: Unplanned Health Care Utilization and Costs in the Huntsman at Home Real-World Trial.

PURPOSE: Patients with cancer experience high rates of morbidity and unplanned health care utilization and may benefit from new models of care. We evaluated an adult oncology hospital at home program's rate of unplanned hospitalizations and health care costs and secondarily, emergency department (ED) use, length of hospital stays, and intensive care unit (ICU) admissions during the 30 days after enrollment. METHODS: We conducted a prospective, nonrandomized, real-world cohort comparison of 367 hospitalized patients with cancer-169 patients consecutively admitted after hospital discharge to Huntsman at Home (HH), a hospital-at-home program, compared with 198 usual care patients concurrently identified at hospital discharge. All patients met clinical criteria for HH admission, but those in usual care lived outside the HH service area. Primary outcomes were the number of unplanned hospitalizations and costs during the 30 days after enrollment. Secondary outcomes included length of hospital stays, ICU admissions, and ED visits during the 30 days after enrollment. RESULTS: Groups were comparable except that more women received HH care. In propensity-weighted analyses, the odds of unplanned hospitalizations was reduced in the HH group by 55% (odds ratio, 0.45, 95% CI, 0.29 to 0.70; P < .001) and health care costs were 47% lower (mean cost ratio, 0.53; 95% CI, 0.39 to 0.72; P < .001) over the 30-day period. Secondary outcomes also favored HH. Total hospital stay days were reduced by 1.1 days (P = .004) and ED visits were reduced by 45% (odds ratio, 0.55; 95% CI, 0.33 to 0.92; P = .022). There was no evidence of a difference in ICU admissions (P = .972). CONCLUSION: This oncology hospital at home program shows initial promise as a model for oncology care that may lower unplanned health care utilization and health care costs.

"I Feel All Alone Out Here": Analysis of Audio Diaries of Bereaved Hospice Family Caregivers During the COVID-19 Pandemic.

The COVID-19 pandemic has dramatically changed social life. This secondary qualitative analysis aimed to better understand the impact of the pandemic on bereaved hospice family caregivers' experiences of social connection and isolation in a time of social distancing and general anxiety. Six caregivers in 3 states recorded audio diaries (N = 59) between March 13 and May 15, 2020. Caregivers were, on average, 56.80 years old (SD, 14.22; range, 32-67 years old) and consisted of spouses (n = 2), adult children (n = 3), and a sibling (n = 1). Using NVIVO 12, caregiver diaries were coded for (1) "social connection" (n = 23), defined as being able to access or seeking informal or formal social support networks; (2) "isolation" (n = 17), defined as being unable or reluctant to access informal or formal social support networks, or feeling alone; and (3) "bereavement processes" (n = 147), informed by the dual process model of bereavement (restoration and loss-oriented stressors). Content analysis revealed that caregivers were able to connect with others despite physical distancing expectations, expressed loneliness and grief while in isolation, and described moving on in the face of uncertainty. Findings provide insight into how caregivers experienced bereavement during the initial period of the pandemic and highlight implications for hospice bereavement services.

AP-2α Regulates S-Phase and Is a Marker for Sensitivity to PI3K Inhibitor Buparlisib in Colon Cancer.

Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer. CRISPR-Cas9 and short hairpin RNA were used to eliminate TFAP2A expression in HCT116 and a panel of colon cancer cell lines. AP-2α target genes were identified with RNA sequencing and chromatin immunoprecipitation sequencing. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts, and phosphorylated histone H3 (PHH3). Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2-M and decreased phosphorylation of AKT, effects that were mediated through regulation of TGM2. Buparlisib (BKM120) repressed in vitro invasiveness of HCT116 and a panel of colon cancer cell lines; however, loss of AP-2α induced resistance to buparlisib. Similarly, buparlisib repressed PHH3 and growth of tumor xenografts and increased overall survival of tumor-bearing mice, whereas, loss of AP-2α induced resistance to the effect of PI3K inhibition. Loss of AP-2α in colon cancer leads to prolonged S-phase through altered activation of AKT leading to resistance to the PI3K inhibitor, Buparlisib. The findings demonstrate an important role for AP-2α in regulating progression through the cell cycle and indicates that AP-2α is a marker for response to PI3K inhibitors. IMPLICATIONS: AP-2α regulated cell cycle through the PI3K cascade and activation of AKT mediated through TGM2. AP-2α induced sensitivity to Buparlisib/BKM120, indicating that AP-2α is a biomarker predictive of response to PI3K inhibitors.