Revisiting Temozolomide's role in solid tumors: Old is gold?

Temozolomide is an imidazotetrazine with a long history in oncology especially for the high grade malignant glioma and metastatic melanoma. However, last year's new indications for its use are added. Its optimum pharmacodynamic profile, its ability to penetrate the blood-brain barrier, the existence of methylation of MGMT in solid tumors which enhances its efficacy, the identification of new agents that can overcome temozolomide's resistance, the promising role of temozolomide in turning immune cold tumors to hot ones, are leading to expand its use in other solid tumors, giving oncologists an additional tool for the treatment of advanced and aggressive neoplasms.

The Role of the Gut Microbiome in Cancer Immunotherapy: Current Knowledge and Future Directions.

Cancer immunotherapy is a treatment modality that aims to stimulate the anti-tumor immunity of the host to elicit favorable clinical outcomes. Immune checkpoint inhibitors (ICIs) gained traction due to the lasting effects and better tolerance in patients carrying solid tumors in comparison to conventional treatment. However, a significant portion of patients may present primary or acquired resistance (non-responders), and thus, they may have limited therapeutic outcomes. Resistance to ICIs can be derived from host-related, tumor-intrinsic, or environmental factors. Recent studies suggest a correlation of gut microbiota with resistance and response to immunotherapy as well as with the incidence of adverse events. Currently, preclinical and clinical studies aim to elucidate the unique microbial signatures related to ICI response and anti-tumor immunity, employing metagenomics and/or multi-omics. Decoding this complex relationship can provide the basis for manipulating the malleable structure of the gut microbiota to enhance therapeutic success. Here, we delve into the factors affecting resistance to ICIs, focusing on the intricate gut microbiome-immunity interplay. Additionally, we review clinical studies and discuss future trends and directions in this promising field.

Evaluating the Role of Probiotics in the Prevention and Management of Age-Related Diseases.

The human lifespan has been significantly increased due to scientific advancements in the management of disease; however, the health span of the aging population does not follow the same trend. Aging is the major risk factor for multimorbidity that is derived from the progressive loss of homeostasis, immunological and stem cell exhaustion, as well as exacerbated inflammation responses. Age-related diseases presenting with high frequencies include neurodegenerative, musculoskeletal, cardiovascular, metabolic diseases and cancer. These diseases can be co-morbid and are usually managed using a disease-specific approach that can eventually lead to polypharmacy, low medication adherence rates and undesired drug-drug interactions. Novel studies suggest targeting the shared biological basis of age-related diseases to retard the onset and manage their manifestations. Harvesting the anti-inflammatory and immunomodulatory capacity of probiotics to tackle the root cause of these diseases, could pose a viable alternative. In this article, a comprehensive review of the effects of probiotic supplementation on the molecular pathogenesis of age-related diseases, and the potential of probiotic treatments as preventative or alleviatory means is attempted. Furthermore, issues on the safety and efficiency of probiotic supplementation, as well as the pitfalls of current clinical studies are discussed, while new perspectives for systematic characterization of probiotic benefits on aged hosts are outlined.

Elderly patients with squamous lung carcinoma: faring better or worse?

INTRODUCTION: Nonsmall cell lung cancer is increasingly diagnosed at an advanced age and squamous cell carcinoma is the commonest histological type encountered in older patients. The clinical course, management, and outcome of squamous lung cancer in the elderly have not been thoroughly studied to date. PATIENTS AND METHODS: We retrospectively analyzed 236 squamous cell lung cancer patients diagnosed in two reference hospitals and compared key epidemiological, clinical, and management features between elderly (>70 years) and younger patients. Sixty-four were aged more than 70 years at diagnosis while 172 were up to 70 years of age. RESULTS: There were no differences between the two groups in gender or stage distribution. No differences were observed in the nature or duration of presenting symptoms, the appearance of pleurisy, atelectasis or vascular invasion, the incidence of distant metastatic spread, or the response to combination chemotherapy. Elderly patients were less fit (performance status 2/3 30 vs 20%, p=0.03), developed hemoptysis more often (56 vs 42%, p=0.04), and presented with smaller tumor primaries (median 4 vs 8 cm, p=0.004). When metastases were present, older patients exhibited a tropism for bony (64 vs 29%, p=0.03) and rarity of brain (5 vs 14%, p=0.03) deposits. Though elderly subjects received chemotherapy (63 vs 82%, p=0.003) or radiotherapy (29 vs 48%, p=0.009) less often than their younger counterparts, they tolerated it well and achieved comparable median time to treatment failure and overall survival (median 17 vs 18 months, log-rank p=0.22). Platinum-based chemotherapy and potentially curative management were applied less often in older patients. CONCLUSIONS: Older patients are less fit, develop bony but not brain metastases, receive antineoplastic treatment less often, and survive as long as younger patients. Squamous lung carcinoma may follow a more indolent clinical course in the elderly, a hypothesis worth validating by case-cohort studies and molecular profiling, with the hope to rationally individualize patient treatment.