Publications by authors named "Wells Messersmith"
Colorectal cancer (CRC) is one of the most prevalent and deadly forms of cancer. It is universally treated with a combination of the DNA damaging chemotherapy drugs irinotecan, 5-Fluorouracil (5-FU), and oxaliplatin. is a novel oncogene that plays critical roles in chromatin remodeling and DNA damage repair, as well as the regulation of malignant gene expression.
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- - Determining the best treatment plan for rectal cancer is complicated, involving choices between curative or palliative surgery and considering impact on bowel function and quality of life, especially for distal rectal cancer patients.
- - Patients with rectal cancer face a higher risk of pelvic recurrence compared to those with colon cancer, making careful patient selection and a multidisciplinary treatment approach essential for better outcomes.
- - Recent updates to the NCCN Guidelines for Rectal Cancer include new treatment options like endoscopic submucosal dissection for early cases, revisions to the total neoadjuvant therapy strategy, and a nonoperative "watch-and-wait" option for patients who respond well to initial therapy.
Article Synopsis
- The study explores the use of a CD73 inhibitor (oleclumab) combined with durvalumab and chemotherapy in treating pancreatic ductal adenocarcinoma (PDAC), targeting immune surveillance evasion.
- Conducted across multiple centers, the trial included patients with metastatic PDAC in two cohorts, assessing safety and response rates with various treatment combinations for the chemotherapy regimens.
- While safety results were acceptable, the trial did not achieve its main goal of demonstrating significant treatment efficacy, although some patients with high CD73 levels showed improved outcomes.
Purpose: Rising rates of early-onset colon cancer (EOCC) present challenges in deciding how to optimally treat patients. Although standard of care for stage II CC is surgical resection, adding chemotherapy for high-risk disease, evidence suggests treatment selection may differ by age. We investigated whether adjuvant chemotherapy (AC) administration rates differ between patients with early- and later-onset stage II CC.
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- The study investigates the impact of preoperative chemo(radio)therapy on patients with localized pancreatic adenocarcinoma, focusing on the rare occurrence of pathological complete response (pCR), where no cancer cells are found post-surgery.
- Conducted in 19 centers across 8 countries with 1758 participants, the research shows that only 4.8% of patients achieved pCR, which is linked to better overall survival rates compared to those who did not achieve pCR.
- Factors influencing the likelihood of pCR included the use of multiagent chemotherapy regimens other than the (m)FOLFIRINOX treatment, highlighting the need for tailored therapeutic approaches.
Article Synopsis
- * The study involved 50 patients who had not responded to at least two previous treatments, resulting in an objective response rate (ORR) of 12%, which was statistically better than historical data.
- * While the combination treatment showed a high disease control rate and acceptable side effects, it did not achieve the primary goal of improving ORR compared to historical controls.
Article Synopsis
- Colorectal cancer (CRC) ranks as the fourth most common cancer and the second deadliest in the U.S.
- Treatment for advanced metastatic CRC includes multiple active drugs used alone or in combination, depending on patient-specific factors.
- The paper reviews the systemic therapy recommendations for metastatic CRC as outlined in the NCCN Guidelines for Colon Cancer.
Purpose: There is a need to increase palliative care access for hospitalized older adults with cancer discharged to a skilled nursing facility (SNF) at risk of poor outcomes. Assessing and Listening to Individual Goals and Needs (ALIGN) is a palliative care intervention developed to address this gap. This study gathered perspectives from clinicians across care settings to describe perceptions on serious illness communication and care coordination for patients with cancer after discharge to a SNF to guide ALIGN refinements.
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- - The study investigated the safety and effectiveness of combining alisertib and sapanisertib in patients with difficult-to-treat solid tumors, focusing on pancreatic adenocarcinoma.
- - A total of 31 patients were treated, and while similar side effects to previous studies were noted, only one patient with breast cancer showed a significant improvement, and pancreatic cancer patients had modest treatment responses.
- - The findings suggest that targeting proteins involved in cell cycle regulation (Aurora A kinase) and tumor growth (mTOR) had limited overall clinical impact, but responses varied based on tumor characteristics and patient treatment history.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is difficult to treat due to its late-stage diagnosis and resistance to most therapies, with Wnt signaling playing a significant role in tumor growth and treatment resistance.
- *Research using patient-derived organoids (PDOs) revealed distinct growth dependencies and responses to Wnt inhibitors, particularly the drug ETC-159, in combination with chemotherapy agents like paclitaxel and gemcitabine.
- *In vivo studies with xenografts showed that the combination of ETC-159 and paclitaxel was more effective at reducing tumor growth than either treatment alone, indicating potential for targeted therapies based on Wnt signaling pathways in pancreatic cancer.
Article Synopsis
- HER2-positive metastatic colorectal cancer (mCRC) requires HER2 testing, and first-line treatment typically involves chemotherapy paired with EGFR inhibitors or bevacizumab based on specific genetic mutations.* -
- For patients with RAS/BRAF wild-type disease, HER2-targeted therapies can be considered in later treatment lines or as first-line treatment for those unable to undergo aggressive therapy, with trastuzumab plus tucatinib being a preferred combination.* -
- Ongoing research is focused on optimizing the use of HER2-targeted therapies, including the sequence and combinations of treatments, as well as the role of predictive biomarkers for better treatment guidance.*
Article Synopsis
- Single-cell technologies allow detailed studies of how specific molecules define cell traits, but challenges like sparse data and cell differences make it tough to model biological variability.
- SCORPION is introduced as a new tool that reconstructs gene regulatory networks from single-cell RNA-sequencing data, providing reliable comparisons across different populations.
- In tests, SCORPION outperformed existing techniques and effectively identified differences in regulatory networks related to cancer, helping to reveal important factors that could affect patient survival.
Article Synopsis
- Pancreatic cancer is known for its poor survival rates, improving slowly compared to other types of cancer.
- Treatment typically involves a combination of chemotherapy, surgery, and radiotherapy, with a focus on how the cancer spreads locally.
- Recent advancements in treatment strategies prompt a need for further research to explore new ways to manage and improve outcomes for pancreatic cancer patients.
Article Synopsis
- - The study investigates how pancreatic ductal adenocarcinoma (PDAC) cells release CSF-1, leading to NLRP3 activation in immune cells, which contributes to an immune-tolerant microenvironment that facilitates tumor growth and drug resistance.
- - Higher NLRP3 expression was observed in PDAC patients, correlating with increased inflammation driven by IL1β, which suppresses CD8+ T-cell activation and promotes tumor expansion.
- - The study highlights the potential of using NLRP3 inhibitors in combination with gemcitabine chemotherapy to enhance immune response and reduce tumor growth, suggesting a new therapeutic target for PDAC treatment.
Article Synopsis
- A study examined the outcomes of patients with isolated lung metastases after surgery for pancreatic ductal adenocarcinoma, hypothesizing that pulmonary metastasectomy could enhance survival with minimal risks.
- Analyzing data from 39 patients, the researchers found that those who had pulmonary metastasectomy lived significantly longer after their recurrence (30.8 months) compared to those who didn't (18.6 months).
- While overall survival rates were similar between groups, patients undergoing the procedure had higher survival rates at 3 years post-diagnosis (100% vs 64%) and 2 years post-recurrence (79% vs 32%), with only minor complications and no related deaths.
Article Synopsis
- The NCCN Clinical Practice Guidelines outline the management of squamous cell anal carcinoma, emphasizing a multidisciplinary approach involving various medical specialties.
- Primary treatment for anal and perianal cancers typically involves chemoradiation, and regular follow-ups are crucial for detecting any recurrence.
- Recent updates to the guidelines have refined staging classifications and systemic therapy recommendations based on new research, improving treatment strategies for metastatic anal carcinoma.
Article Synopsis
- The study aimed to evaluate the effectiveness, safety, and maximum tolerated dose (MTD) of palbociclib combined with nab-paclitaxel for treating advanced pancreatic ductal adenocarcinoma (PDAC).
- Preclinical tests showed that this combination outperformed gemcitabine plus nab-paclitaxel in most cases, with some safety concerns leading to a maximum tolerated dose of palbociclib at 100 mg per cycle alongside nab-paclitaxel at 125 mg.
- Although the treatment showed promise, the targeted 12-month survival rate of 65% was not achieved, indicating a need for further research.
Article Synopsis
- Cabozantinib, a multi-tyrosine kinase inhibitor (TKI), showed promising efficacy in treating metastatic colorectal cancer (mCRC), outperforming regorafenib in preclinical studies.
- A phase II clinical trial with 44 patients assessed its effectiveness, revealing that 45% experienced progression-free survival (PFS) after 12 weeks, with a median overall survival of 8.3 months.
- Despite some serious adverse events reported, the study concluded that cabozantinib could be a viable treatment option for mCRC patients who have exhausted other therapies, warranting further research.
Article Synopsis
- The study investigates the effects of adjuvant chemotherapy on survival rates in rectal cancer patients who have achieved a pathologic complete response after neoadjuvant chemoradiotherapy and total mesorectal excision.
- It included data from over 20,000 patients, focusing on those who received or did not receive adjuvant therapy, with findings indicating a significant survival advantage for those who underwent the additional treatment.
- Results showed that patients who received adjuvant chemotherapy had a 5, 10, and 14-year survival rate of 93%, 85%, and 83%, respectively, compared to 87%, 67%, and 51% for those who did not receive it, suggesting a critical benefit
Article Synopsis
- Scientists found that a medicine called cabozantinib can help a type of cancer called MSS-CRC work better with another medicine, nivolumab, which usually only helps a different type, MSI-high CRC.
- They tested this combination on special mice with human immune systems and saw that it made the tumors grow slower in most of their experiments.
- The study suggests that this combination might be worth trying in real-life tests with cancer patients who have MSS-CRC to see if it helps them too!
Article Synopsis
- AZD0156, an oral ATM inhibitor, was tested in combination with irinotecan and 5-fluorouracil (5FU) to see if it enhances the effectiveness of chemotherapy in treating colorectal cancer (CRC).
- In vitro studies showed that the combination led to increased cell death and G2/M phase cell cycle arrest, suggesting improved anti-cancer effects compared to single-agent treatments.
- Results from patient-derived xenograft models indicated that this combination therapy resulted in greater tumor growth inhibition, although the effectiveness varied across different models.
Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.
J Natl Compr Canc Netw
October 2022
Article Synopsis
- The NCCN Guidelines for Rectal Cancer have been updated to improve the management of malignant polyps and nonmetastatic rectal cancer, emphasizing new approaches.
- Key updates include revised algorithms for stage II and III rectal cancer that highlight the role of total neoadjuvant therapy and expanded short-course radiation recommendations.
- The guidelines also introduce a "watch-and-wait" strategy for patients who respond fully to neoadjuvant therapy, while the complete guidelines address risk assessment, management of metastatic disease, and posttreatment care.
Background: This phase I multicenter study was designed to evaluate the safety, tolerability, efficacy, and translational effects on the tumor microenvironment of itacitinib (Janus-associated kinase 1 (JAK1) inhibitor) in combination with epacadostat (indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor) or parsaclisib (phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor).
Methods: Patients with advanced or metastatic solid tumors were enrolled and received itacitinib (100-400 mg once a day) plus epacadostat (50-300 mg two times per day; group A), or itacitinib (100-400 mg once a day) plus parsaclisib or parsaclisib monotherapy (0.3-10 mg once a day; group B).