Insulin resistance (IR) is a prevalent metabolic condition characterized by reduced cellular responsiveness to insulin and consequent hyperinsulinemia, and it is a key component of type 2 diabetes and metabolic syndrome. A growing body of evidence suggests IR is a critical accomplice in the pathogenesis of various cancers. This review synthesizes evidence on underlying molecular mechanisms, including the integrated roles of the insulin/IGF system, chronic inflammation, metabolic reprogramming, and mitochondrial dysfunction. This review proposes that metabolic dysregulation should be viewed as a modifiable oncogenic force. This perspective illuminates new pathways for understanding cancer development and offers promising avenues for prevention and therapeutic intervention.

Cancer is a leading cause of death worldwide and it can affect almost every part of the human body. Effective screening and early diagnosis of cancers is extremely difficult due to the multifactorial etiology of the disease and delayed presentation of the patients. The available treatments are usually not specific to the affected organ system, leading to intolerable systemic side effects and early withdrawal from therapies. In vivo and in vitro studies have revealed an association of specific microbiome signatures with individual cancers. The cancer-related human microbiome has also been shown to affect the response of tissues to chemotherapy, immunotherapy, and radiation. This is an excellent opportunity for us to design specific screening markers using the microbiome to prevent cancers and diagnose them early. We can also develop precise treatments that can target cancer-affected specific organ systems and probably use a lesser dose of chemotherapy or radiation for the same effect. This prevents adverse effects and early cessation of treatments. However, we need further studies to exactly clarify and characterize these associations. In this review article, we focus on the association of the microbiome with individual cancers and highlight its future role in cancer screenings, diagnosis, prognosis, and treatments.

Introduction and importance: Renal cell carcinoma (RCC) represents 90% of renal malignancies with rising global incidence. While the classic triad includes hematuria, flank pain, and palpable masses, paraneoplastic hypercalcemia occurs in 17% of cases and indicates aggressive disease behavior. This case documents severe hypercalcemia as the initial manifestation of metastatic RCC. Case presentation: A 64-year-old male presented with malaise, bloating, and weight loss. Laboratory evaluation revealed severe hypercalcemia (15.1 mg/dL), suppressed parathyroid hormone (4.2 pg/mL), and elevated parathyroid hormone-related peptide (83 pg/mL). Imaging identified a 5.5 × 5.0 × 5.3 cm left renal mass with metastases to lungs, brain, and possibly bone. Biopsy confirmed metastatic clear-cell RCC. Management comprised aggressive hydration, zoledronic acid, combined immunotherapy (pembrolizumab/lenvatinib), and palliative radiation for cerebral lesions. Clinical discussion: This case illustrates PTHrP-mediated humoral hypercalcemia of malignancy in metastatic RCC. The pathophysiology differs from alternative mechanisms such as calcitriol-mediated hypercalcemia or cytokine-driven osteoclast activation. Diagnostic markers demonstrated a classic humoral pattern with PTHrP elevation (83 pg/mL) and PTH suppression (4.2 pg/mL). The multimodal imaging protocol effectively delineated primary tumor dimensions, vascular invasion, and metastatic burden. Treatment efficacy was objectively measured through serial calcium levels and documented radiographic regression of primary and metastatic lesions. This aligns with recent data on combination immunotherapy (anti-PD-1) with tyrosine kinase inhibition in advanced RCC, supporting current therapeutic paradigms for PTHrP-mediated hypercalcemia in metastatic disease. Conclusion: Prompt recognition of paraneoplastic hypercalcemia in RCC facilitates timely intervention. This case demonstrates the value of comprehensive diagnostic evaluation and multidisciplinary management combining supportive care with targeted immunotherapy. Further prospective studies are needed to optimize therapeutic strategies for patients presenting with metabolic derangements suggestive of underlying malignancy.

Introduction and importance: Pulmonary mucormycosis (PM) is a severe fungal infection threatening immunocompromised individuals, especially with uncontrolled diabetes. Co-infection with bacteria like Achromobacter xylosoxidans complicates management. We report a rare and fatal case of PM co-infected with A. xylosoxidans , which was further complicated by a subsequent SARS-CoV-2 superinfection. Case presentation: A 55-year-old female with poorly controlled type 2 diabetes mellitus and multiple comorbidities presented with worsening dyspnea. Investigations revealed severe hyperglycemia (927 mg/dL), hyponatremia, and imaging showed a large right upper lobe cavitary lesion. Bronchoscopy confirmed acute necrotizing pneumonia with Zygomycetes (Mucor) elements and grew >100 000 CFU/mL A. xylosoxidans/denitrificans . Computed tomography also revealed extensive nasopharyngeal mucormycosis. Her hospital course was complicated by a hyperosmolar hyperglycemic state, pulseless electrical activity cardiac arrest secondary to hemoptysis, and a subsequent SARS-CoV-2 superinfection, ultimately resulting in death. Clinical discussion: This case exemplifies the diagnostic difficulties of PM, often mimicking other pulmonary conditions and requiring invasive testing for confirmation. Uncontrolled diabetes was a critical predisposing factor. The presence of A. xylosoxidans , an intrinsically resistant bacterium, alongside PM created significant therapeutic hurdles. The subsequent SARS-CoV-2 superinfection likely further compromised the patient’s critical status. The subsequent SARS-CoV-2 infection likely further compromised the patient’s status. The case underscores the lethal synergy of these sequential opportunistic infections, and the poor prognosis associated with PM, especially when compounded by critical illness and co-infections. Conclusion: High suspicion for invasive fungal infections is crucial in high-risk patients with refractory pneumonia. Prompt invasive diagnostics and awareness of bacterial co-pathogens are essential, as outcomes remain poor despite aggressive therapy.