Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, necessitating the continuous evolution of therapeutic approaches. Despite advancements in early detection and localized treatments, metastatic colorectal cancer (mCRC) poses significant challenges due to low survival rates and resistance to conventional therapies. This review highlights the current landscape of CRC treatment, focusing on chemotherapy and targeted therapies. Chemotherapeutic agents, including 5-fluorouracil, irinotecan, and oxaliplatin, have significantly improved survival but face limitations such as systemic toxicity and resistance. Targeted therapies, leveraging mechanisms like VEGF, EGFR, and Hedgehog pathway inhibition, offer promising alternatives, minimizing damage to healthy tissues while enhancing therapeutic precision. Furthermore, future directions in CRC treatment include exploring innovative targets such as Wnt/β-catenin, Notch, and TGF-β pathways, alongside IGF/IGF1R inhibition. These emerging strategies aim to address drug resistance and improve patient outcomes. This review emphasizes the importance of integrating molecular insights into drug development, advocating for a more personalized approach to combat CRC’s complexity and heterogeneity.

Background/Objectives: Peripheral neuropathy affects up to 50% of people living with HIV (PLWH). Currently, no small translational rodent model accurately replicates the peripheral neuropathy observed in PLWH. The primary objectives of this study are to assess whether HIV transgenic (HIV-tg) rats develop peripheral neuropathy with pathological and pain-like behaviors similar to those observed in PLWH and to evaluate the analgesic effects of the non-psychoactive cannabis compounds cannabidiol (CBD) and β-caryophyllene (BCP) in HIV-related neuropathic pain. Methods: We used a comprehensive set of behavioral, pharmacological, molecular, biochemical, and proteomic approaches. Results: Tissue analyses showed that HIV-tg rats had significantly reduced intra-epidermal nerve fiber density and increased macrophage infiltration in the dorsal root ganglion compared with control wild-type rats. Behavioral assessments demonstrated that HIV-tg rats developed mechanical allodynia and ongoing pain. β-caryophyllene (BCP) demonstrated higher efficacy than cannabidiol (CBD) in alleviating HIV-related neuropathic pain. Proteomic analysis identified specific proteins uniquely modulated by the analgesic effects of BCP compared to vehicle in HIV-tg rats with peripheral neuropathy and neuropathic pain. Conclusions: The findings indicate that HIV-tg rats develop peripheral neuropathy and neuropathic pain comparable to those observed in PLWH. BCP is more effective than cannabidiol (CBD) in alleviating HIV-related neuropathic pain. Furthermore, the data suggest that BCP modulates specific proteins that may contribute to its analgesic effects in the HIV-tg model of neuropathic pain, without inducing central side effects.

Background: Lung adenocarcinoma (LUAD) is the most prevalent histologic subtype of non-small cell lung cancer (NSCLC) and exhibits considerable molecular heterogeneity. Among the most clinically significant driver alterations are mutations in EGFR and KRAS, both of which influence treatment selection and oncologic outcomes. The prevalence of these mutations varies by race, yet racial minority populations remain underrepresented in genomic studies. EGFR alterations are more frequently observed in Asian patients, while KRAS mutations predominate in non-Asian cohorts. This study aimed to characterize race-associated differences in driver mutation prevalence among Asian, Black, and White patients with LUAD. Methods: A retrospective secondary cohort analysis was performed using publicly available clinicogenomic data from the Lung Adenocarcinoma Met Organotropism cohort, accessed via cBioPortal, comprising 2653 tumor samples. Patients were stratified by self-reported race into Asian, Black, and White cohorts; cases with missing race data were denoted as either other or unknown. Mutation frequencies for EGFR, KRAS, and TP53 were extracted from OncoPrint cohort study views and compared descriptively across groups. Results: Distinct race-associated differences in driver mutation prevalence were observed. Asian patients exhibited the highest frequency of EGFR alterations (64%), compared with Black (41%) and White (28%) cohorts. In contrast, KRAS mutations were least prevalent in Asian patients (10%) and more frequent in White (33%) and Black (23%) cohorts, indicating an inverse distribution between Asian and non-Asian populations. TP53 mutation prevalence was similar in Asian (52%) and White (53%) cohorts but was notably higher in Black patients (65%). Conclusions: Asian patients with LUAD exhibit a distinct molecular profile characterized by EGFR predominance, with direct implications for eligibility for EGFR-targeted tyrosine kinase inhibitor therapy. Black patients may also benefit from EGFR-based targeted therapies, but lack of large genomic data on Black populations warrants further investigation. White cohorts display a KRAS-dominant mutation pattern, suggesting divergent tumorigenic pathways and the potential need for alternative therapeutic strategies. The elevated TP53 frequency in Black patients remains to be further characterized. These findings support integrating race-associated genomic profiling into precision oncology frameworks to improve treatment selection and reduce disparities in outcomes.

Colorectal cancer (CRC) remains the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide