Light-activated conjugated polymer nanoparticles to defeat pathogens associated with bovine mastitis.

Bovine mastitis (BM) represents a significant challenge in the dairy industry. Limitations of conventional treatments have prompted the exploration of alternative approaches, such as photodynamic inactivation (PDI). In this study, we developed a PDI protocol to eliminate BM-associated pathogens using porphyrin-doped conjugated polymer nanoparticles (CPN). The PDI-CPN protocol was evaluated in four mastitis isolates of Staphylococcus and in a hyper-biofilm-forming reference strain. The results in planktonic cultures demonstrated that PDI-CPN exhibited a bactericidal profile upon relatively low light doses (∼9.6 J/cm2). Furthermore, following a seven-hour incubation period, no evidence of cellular reactivation was observed, indicating a highly efficient post-photodynamic inactivation effect. The successful elimination of bacterial suspensions encouraged us to test the PDI-CPN protocol on mature biofilms. Treatment using moderate light dose (∼64.8 J/cm2) reduced biofilm biomass and metabolic activity by up to 74% and 88%, respectively. The impact of PDI-CPN therapy on biofilms was investigated using scanning electron microscopy (SEM), which revealed nearly complete removal of the extracellular matrix and cocci. Moreover, ex vivo studies conducted on bovine udder skin demonstrated the efficacy of the therapy in eliminating bacteria from these scaffolds and its potential as a prophylactic method. Notably, the histological analysis of skin revealed no signs of cellular degeneration, suggesting that the protocol is safe and effective for BM treatment. Overall, this study demonstrates the potential of PDI-CPN in treating and preventing BM pathogens. It also provides insights into the effects of PDI-CPN on bacterial growth, metabolism, and survival over extended periods, aiding the development of effective control strategies and the optimization of future treatments.

A comparison of three techniques for the osteosynthesis after minimal invasive osteotomies for hallux valgus.

PURPOSE: Third and fourth-generation minimal invasive osteotomies (MIO) for the treatment of hallux valgus (HV) have become popular procedures worldwide with promising results due to the improvement in the fixation method. The tricortical cannulated screw placement remains a complex procedure that is technically challenging and requires a long skill learning curve with high radiation exposure mainly in the form of intensifier shots (IS) required for the MIO fixation. This study aims to compare the number of X-ray IS required using three different techniques for the cannulated guide placement. METHODS: A retrospective cross-sectional observational and comparative study was conducted to assess the number of X-rays IS required for correct cannulated screw guide placement using three different techniques: traditional perforator, the drill and joystick, and K-wire first techniques. RESULTS: A total of 53 MIS procedures from thirty-one patients in two different hospitals were included. IS X-rays were 155.1 ± 29.7 in the traditional technique (n = 14), 143.0 ± 43.2 in the drill and joystick technique (n = 22), and 85 ± 18.7 in the K-wires first technique (n = 17), p = < 0.001 using one-way ANOVA. CONCLUSIONS: The K-wire first technique statistically significantly decreases X-ray IS numbers p ≤ 0.001. There were no statistically significant differences between the traditional (after osteotomy K-wire placement) and the drill and joystick techniques (p = 0.36).

Proficiency Levels and Validity Evidence for Scoring Metrics for a Virtual Reality and Inanimate Robotic Surgery Simulation Curriculum.

OBJECTIVE: Our institution recently implemented a virtual reality (VR) skills curriculum for general surgery residents using the SimNow simulator. Based on a content alignment study, we revised the curriculum to include only 20 of 33 VR tasks and we added 3 previously validated inanimate tasks. The purpose of this study was to establish expert-derived proficiency levels for all tasks and to evaluate the validity of the scoring for the VR tasks. DESIGN: Two expert robotic surgeons performed 5 repetitions of each VR and inanimate task. The trimmed mean (lowest scoring attempt and outliers [>2 standard deviations] were eliminated) was defined as the expert level for each task. For the VR tasks, expert levels were compared to resident performance to evaluate validity. SETTING: This study was conducted at the University of Texas Southwestern Medical Center (Dallas, TX), a tertiary care academic teaching hospital. PARTICIPANTS: Two expert robotic surgeons participated in this study. The data from 42 residents (PGY2-4) who completed the original curriculum was used to represent novice performance. RESULTS: Comparison of expert levels and resident performance was statistically significant for 15 VR tasks (supporting validity) and approached significance (p = 0.06, 0.09) for 2 VR tasks; expert levels were designated as proficiency levels for these 17 tasks. Group comparisons were clearly not significant (p = 0.2-0.8) for 3 VR tasks; 2 of these 3 tasks were retained as introductory exercises (with 3 repetitions required) and 1 was excluded. For the 3 inanimate tasks, expert levels minus 2 standard deviations were designated as proficiency levels. CONCLUSIONS: This analysis generated validity evidence for 15 VR tasks and established expert-derived proficiency levels for 17 VR tasks and 3 inanimate tasks. Our proposed curriculum now consists of 19 VR and 3 inanimate tasks using the selected proficiency levels. We anticipate that this design will maximize curriculum efficiency and effectiveness.

Association of race, demographic and socioeconomic factors with failure to rescue after hepato-pancreato-biliary surgery in the United States.

BACKGROUND: We aimed to describe the association of patient-related factors such as race, socioeconomic status, and insurance on failure to rescue (FTR) after hepato-pancreato-biliary (HPB) surgeries. METHODS: Using the National Inpatient Sample, we analyzed 98,788 elective HPB surgeries between 2004 and 2017. Major and minor complications were identified using ICD9/10 codes. We evaluated mortality rates and FTR (inpatient mortality after major complications). We used multivariate logistic regression analysis to assess racial, socioeconomic, and demographic factors on FTR, adjusting for covariates. RESULTS: Overall, 43 % of patients (n = 42,256) had pancreatic operations, 36% (n = 35,526) had liver surgery, and 21% (n = 21,006) had biliary interventions. The overall major complication rate was 21% (n = 20,640), of which 8% (n = 1655) suffered FTR. Factors independently associated with increased risk for FTR were male sex, older age, higher Charlson Comorbidity Index, Hispanic ethnicity, Asian or other race, lower income quartile, Medicare insurance, and southern region hospitals. CONCLUSIONS: Medicare insurance, male gender, Hispanic ethnicity, and lower income quartile were associated with increased risk for FTR. Efforts should be made to improve the identification and subsequent treatment of complications for those at high risk of FTR.

Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites.

BACKGROUND: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. METHODS: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era. RESULTS: Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04). CONCLUSIONS: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

Cost Analysis and Financial Implications of a Peritoneal Surface Malignancy Program in the USA.

BACKGROUND: We aimed to describe the financial implications of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in the USA. MATERIALS AND METHODS: We conducted a retrospective cost analysis of 100 CRS/HIPEC procedures to examine the impact of patient and procedural factors on hospital costs and reimbursement. A comparison of surgeons' work relative value units (wRVUs) between CRS/HIPEC and a representative sample of complex surgical oncology procedures was made to assess the physicians' compensation rate. Univariable and multivariable backward logistic regression was used to analyze the association between perioperative variables and high direct cost (HDCs). RESULTS: The median direct cost per CRS/HIPEC procedure was US $44,770. The median hospital reimbursement was US $43,066, while professional reimbursement was US $8608, resulting in a positive contribution margin of US $7493/procedure. However, the contribution margin significantly varied with the payer mix. Privately insured patients had a positive median contribution margin of US $23,033, whereas Medicare-insured patients had a negative contribution margin of US $13,034. Length of stay (LOS) had the most significant association with HDC, and major complications had the most significant association with LOS. Finally, CRS/HIPEC procedures generated a median of 13 wRVU/h, which is significantly lower than the wRVU/h generated by open pancreatoduodenectomies, open gastrectomies, and hepatectomies. However, higher operation complexity and multiple visceral resections help compensate for the relatively low wRVU/h. CONCLUSIONS: CRS/HIPEC is an expensive operation, and prolonged LOS has the most significant impact on the total cost of the procedure. High-quality care is essential to improve patient outcomes and maintain the economic sustainability of the procedure.

Baseline performance in a robotic virtual reality platform predicts rate of skill acquisition in a proficiency-based curriculum: a cohort study of surgical trainees.

BACKGROUND: Residency programs must prepare to train the next generation of surgeons on the robotic platform. The purpose of this study was to determine if baseline skills of residents on a virtual reality (VR) robotic simulator before intern year predicted future performance in a proficiency-based curriculum. METHODS: Across two academic years, 21 general surgery PGY-1s underwent the robotic surgery boot camp at the University of Texas Southwestern. During boot camp, subjects completed five previously validated VR tasks, and their performance metrics (score, time, and economy of motion [EOM]) were extracted retrospectively from their Intuitive learning accounts. The same metrics were assessed during their residency until they reached previously validated proficiency benchmarks. Outcomes were defined as the score at proficiency, attempts to reach proficiency, and time to proficiency. Spearman's rho and Mann-Whitney U tests were used; median (IQR) was reported. Significance level was set at p < 0.05. RESULTS: Twenty-one residents completed at least three out of the five boot camp tasks and achieved proficiency in the former during residency. The median average score at boot camp was 12.3 (IQR: 5.14-18.5). The median average EOM at boot camp was 599.58 cm (IQR: 529.64-676.60). The average score at boot camp significantly correlated with lower time to achieve proficiency (p < 0.05). EOM at boot camp showed a significant correlation with attempts to proficiency and time to proficiency (p < 0.01). Residents with an average baseline EOM below the median showed a significant difference in attempts to proficiency (p < 0.05) and time to proficiency (p < 0.05) compared to those with EOMs above or equal to the median. CONCLUSION: Residents with an innate ability to perform tasks with better EOM may acquire robotic surgery skills faster. Future investigators could explore how these innate differences impact performance throughout residency.

Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.

Defining the Price Tag of Complications Following Pancreatic Surgery: A US National Perspective.

INTRODUCTION: Pancreatic surgery tends to have a high rate of postoperative complications due to its complex nature, significantly increasing hospital costs. Our aim was to describe the true association between complications and hospital costs in a national cohort of US patients. METHODS: The National Inpatient Sample was used to conduct a retrospective analysis of elective pancreatic resections performed between 2004 and 2017, categorizing them based on whether patients experienced major complications (MaC), minor complications (MiC), or no complications (NC). Multivariable quantile regression was used to analyze how costs varied at different percentiles of the cost curve. RESULTS: Of 37,893 patients, 45.3%, 28.6%, and 26.1% experienced NC, MiC, and MaC, respectively. Factors associated with MaC were a Charlson Comorbidity Index of ≥4, prolonged length of stay, proximal pancreatectomy, older age, male sex, and surgery performed at hospitals with a small number of beds or at urban nonteaching hospitals (all P < 0.01). Multivariable quantile regression revealed significant variation in MiC and MaC across the cost curve. At the 50th percentile, MiC increased the cost by $3352 compared to NC while MaC almost doubled the cost of the surgery, increasing it by $20,215 (both P < 0.01). The association between complications and cost was even greater at the 95th percentile, increasing the cost by $10,162 and $108,793 for MiC and MaC, respectively (P < 0.01). CONCLUSIONS: MiC and MaC were significantly associated with increased hospital costs. Furthermore, the relationship between MaC and costs was especially apparent at higher percentiles of the cost curve.

Gallstone Ileus in a Young Patient: A Clinical Case Report and Literature Review.

Gallstone ileus is a rare presentation of gallbladder disease. It is mostly encountered in female and elderly patients. It occurs when a stone causes a fistula between the gallbladder and the intestinal lumen. More than half of the patients do not have a history of biliary disease. Surgical intervention is still considered the best treatment option; however, the best choice between one-stage and two-stage surgery is still unknown. We present a gallstone Ileus case in a patient with uncommon epidemiological characteristics: a 28-year-old male Hispanic patient without a gallbladder disease history.

Developing a Robotic Surgery Curriculum: Selection of Virtual Reality Drills for Content Alignment.

INTRODUCTION: Despite the importance of simulation-based training for robotic surgery, there is no consensus about its training curricula. Recently, a virtual reality (VR) platform (SimNow, Intuitive, Inc) was introduced with 33 VR drills but without evidence of their validity. As part of our creating a new robotic VR curriculum, we assessed the drills' validity through content mapping and the alignment between learning goals and drill content. METHODS: Three robotically trained surgeons content-mapped all 33 drills for how well the drills incorporated 15 surgery skills and also rated the drills' difficulty, usefulness, relevance, and uniqueness. Drills were added to the new curriculum based on consensus about ratings and historic learner data. The drills were grouped according to similar skill sets and arranged in order of complexity. RESULTS: The 33 drills were judged to have 12/15 surgery skills as primary goals and 13/15 as secondary goals. Twenty of the 33 drills were selected for inclusion in the new curriculum; these had 11/15 skills as primary goals and 11/15 as secondary goals. However, skills regarding energy sources, atraumatic handling, blunt dissection, fine dissection, and running suturing were poorly represented in the drills. Three previously validated inanimate drills were added to the curriculum to address lacking skill domains. CONCLUSIONS: We identified 20 of the 33 SimNow drills as a foundation for a robotic surgery curriculum based on content-oriented evidence. We added 3 other drills to address identified gaps in drill content.

LncRNAs-associated to genomic instability: A barrier to cancer therapy effectiveness.

Although a large part of the genome is transcribed, only 1.9% has a protein-coding potential; most of the transcripts are non-coding RNAs such as snRNAs, tRNAs, and rRNAs that participate in mRNA processing and translation. In addition, there are small RNAs with a regulatory role, such as siRNAs, miRNAs, and piRNAs. Finally, the long non-coding RNAs (lncRNAs) are transcripts of more than 200 bp that can positively and negatively regulate gene expression (both in cis and trans), serve as a scaffold for protein recruitment, and control nuclear architecture, among other functions. An essential process regulated by lncRNAs is genome stability. LncRNAs regulate genes associated with DNA repair and chromosome segregation; they are also directly involved in the maintenance of telomeres and have recently been associated with the activity of the centromeres. In cancer, many alterations in lncRNAs have been found to promote genomic instability, which is a hallmark of cancer and is associated with resistance to chemotherapy. In this review, we analyze the most recent findings of lncRNA alterations in cancer, their relevance in genomic instability, and their impact on the resistance of tumor cells to anticancer therapy.

[Particulate matter PM10, NO2 and exacerbations of chronic respiratory diseases]. / Partículas en suspensión PM10, NO2 y agudizaciones de enfermedad respiratoria crónica.

OBJECTIVES: The new World Health Organization guidelines recommend studies with simultaneous exposure to multiple air pollutants. The main objective has been to analyze the strength of the association between different concentrations of PM10 and NO2 and the exacerbation of chronic respiratory diseases (ECRD), specifically asthma and chronic obstructive pulmonary disease. MATERIAL AND METHODS: Retrospective cross-sectional study. The population analyzed were adults treated in an urgent and primary health care center on certain lag+1 days in 2019. Three indices have been developed (1: high levels of PM10 and NO2; 2: high level of PM10 and low level of NO2, and 3: low levels of PM10 and NO2) and a logistic regression model for each of them, with ECRD as the outcome variable, and the progressive addition of adjustment variables (sex, age, tobacco, Charlson index, season, precipitation, wind and temperature). RESULTS: Four hundred and sixty-one people were analyzed, 17 with ECRD. Models 1 and 2 presented very similar values in the adjusted OR (4.28 [95% CI 1.05-17]), R2 (0.88) and the area under the ROC curve (>0.72). In both of them the significance was maintained after including the adjustment variables, while model 3 only allowed the addition of precipitation. The inclusion of the Charlson index and the tobacco consumption in the 3 models implied the loss of statistical significance of the PM10/NO2 combination regarding ECRD. CONCLUSIONS: High levels of PM10 are related to ECRD and have a greater impact than NO2, with tobacco use and comorbidities being the main precipitants of ECRD.

Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy.

Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-ß gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer of ICD, could further potentiate treatment efficacy without inducing cardiotoxicity, a critical side effect of Dox. Using central composite rotational design analysis, we show that cooperation between gene transfer and chemotherapy killed MCA205 and B16F10 cells and permitted the application of reduced viral and drug doses. The treatments also cooperated to induce elevated levels of ICD markers in MCA205, which correlated with improved efficacy of immunotherapy in vivo. Treatment of subcutaneous MCA205 tumors associating gene transfer and low dose (10 mg/kg) chemotherapy resulted in inhibition of tumor progression. Moreover, the reduced dose did not cause cardiotoxicity as compared to the therapeutic dose of Dox (20 mg/kg). The association of p19Arf/interferon-ß gene transfer and Dox chemotherapy potentiated antitumor response and minimized cardiotoxicity.

A Critical Analysis of the Automated Hematology Assessment in Pregnant Women at Low and at High Altitude: Association between Red Blood Cells, Platelet Parameters, and Iron Status.

The objectives of the study were to determine differences in the parameters of red blood cells (RBC), white blood cells (WBC), and platelets at low altitude (LA) and at high altitude (HA) and with the gestation being advanced, and to determine correlations between parameters of RBC and platelets. We also studied the association of RBC and platelets with markers of iron status. In addition, markers of iron status and inflammation were measured and compared at each trimester of gestation in pregnant women at LA and HA. A cross-sectional comparative study was conducted at Lima (150 m above sea level) and Cusco at 3400 m above sea level from May to December 2019. Hematological parameters in pregnant women (233 at LA and 211 at HA) were analyzed using an automated hematology analyzer. Serum ferritin levels, soluble transferrin receptor (sTfR), hepcidin, erythropoietin, testosterone, estradiol, and interleukin-6 (IL6) levels were measured by ELISA. One-way ANOVA supplemented with post hoc test, chi-square test, and Pearson correlation test statistical analyses were performed. p < 0.05 was considered significant. Pregnant woman at HA compared to LA had significantly lower WBC (p < 0.01), associated with higher parameters of the RBC, except for the mean corpuscular volume (MCV) that was no different (p > 0.05). Platelets and mean platelet volume (MPV) were higher (p < 0.01), and platelet distribution width (PDW) was lower at HA than at LA (p < 0.01). A higher value of serum ferritin (p < 0.01), testosterone (p < 0.05), and hepcidin (p < 0.01) was observed at HA, while the concentration of sTfR was lower at HA than at LA (p < 0.01). At LA, neutrophils increased in the third trimester (p < 0.05). RBC parameters decreased with the progress of the gestation, except RDW-CV, which increased. The platelet count decreased and the MPV and PDW were significantly higher in the third trimester. Serum ferritin, hepcidin, and serum testosterone decreased, while sTfR and serum estradiol increased during gestation. At HA, the WBC and red blood cell distribution width- coefficient of variation (RDW-CV), PCT, and serum IL-6 did not change with gestational trimesters. RBC, hemoglobin (Hb), hematocrit (Hct), mean corpuscular hemoglobin concentration (MCHC), and platelet count were lower as gestation advanced. MCV, MPV, and PDW increased in the third trimester. Serum ferritin, testosterone, and hepcidin were lower in the third trimester. Serum estradiol, erythropoietin, and sTfR increased as gestation progressed. Direct or inverse correlations were observed between RBC and platelet parameters and LA and HA. A better number of significant correlations were observed at HA. Hb, Hct, and RDW-CV showed a significant correlation with serum ferritin at LA and HA. Of these parameters, RDW-CV and PDW showed an inversely significant association with ferritin (p < 0.05). In conclusion, a different pattern was observed in hematological markers as well as in iron status markers between pregnant women at LA and HA. In pregnant women a significant correlation between several RBC parameters with platelet marker parameters was also observed. Data suggest that pregnant women at HA have adequate iron status during pregnancy as reflected by higher serum ferritin levels, lower sTfR levels, and higher hepcidin values than pregnant women at LA.

The Influence of Oncogenic RAS on Chemotherapy and Radiotherapy Resistance Through DNA Repair Pathways.

RAS oncogenes are chief tumorigenic drivers, and their mutation constitutes a universal predictor of poor outcome and treatment resistance. Despite more than 30 years of intensive research since the identification of the first RAS mutation, most attempts to therapeutically target RAS mutants have failed to reach the clinic. In fact, the first mutant RAS inhibitor, Sotorasib, was only approved by the FDA until 2021. However, since Sotorasib targets the KRAS G12C mutant with high specificity, relatively few patients will benefit from this therapy. On the other hand, indirect approaches to inhibit the RAS pathway have revealed very intricate cascades involving feedback loops impossible to overcome with currently available therapies. Some of these mechanisms play different roles along the multistep carcinogenic process. For instance, although mutant RAS increases replicative, metabolic and oxidative stress, adaptive responses alleviate these conditions to preserve cellular survival and avoid the onset of oncogene-induced senescence during tumorigenesis. The resulting rewiring of cellular mechanisms involves the DNA damage response and pathways associated with oxidative stress, which are co-opted by cancer cells to promote survival, proliferation, and chemo- and radioresistance. Nonetheless, these systems become so crucial to cancer cells that they can be exploited as specific tumor vulnerabilities. Here, we discuss key aspects of RAS biology and detail some of the mechanisms that mediate chemo- and radiotherapy resistance of mutant RAS cancers through the DNA repair pathways. We also discuss recent progress in therapeutic RAS targeting and propose future directions for the field.