PTHLH (Parathyroid Hormone Like Hormone)

These meta-analyses underscore the need for robust multivariate analyses in women to rigorously re-evaluate the role of PTHrP in breast cancer. This is important since the gene coding for PTHrP (PTHLH) has been consistently identified as a breast cancer susceptibility locus.

Pamidronate (APD), a nitrogen-containing bisphosphonate, has shown potential in managing osteolytic lesions by inhibiting osteoclast activity...Moreover, CHA exhibited excellent biocompatibility with no observed systemic toxicity. These results underscore the promise of CHA as a clinically translatable therapeutic strategy for the treatment of osteolytic bone metastases.

Moreover, these tumors also showed lower expression of tumor proliferative and neuron markers. Together these findings established cancer cell secreted PTHLH as a critical mediator of immunosuppression and neuron infiltrations in HNSCC, particularly in tongue tumor.

Imatinib normalized calcium and parathyroid hormone levels and induced tumor regression...4D-CT and FCH-PET/CT can be used as alternative imaging modalities following 99mTc-sestamibi SPECT/CT to locate ectopic parathyroid lesions. The mechanism behind GIST-related hypercalcemia may involve the expression of PTHrP or 1-alpha-hydroxylase in tumor tissues.

Consistent with these observations, two different allosteric HIF2 inhibitors, belzutifan and NKT2152, rapidly ameliorated hypercalcemia and cachexia in patients with ccRCC, including in some who did not exhibit objective tumor shrinkage. Our findings support prospective clinical studies to determine whether HIF2 inhibitors can be leveraged not only for tumor control, but also for the treatment of cancer-associated cachexia in renal cell carcinoma.

Discontinuation of calcium/vitamin D supplementation and initiation of low-dose prednisolone and fludrocortisone led to resolution of hypercalcemia and renal impairment. This case highlights the importance of recognizing dual non-malignant etiologies in cancer survivors with suppressed PTH/PTHrP and persistent hypercalcemia, particularly when urinary calcium excretion remains high despite renal impairment.

High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.

Further, we show that the increased PTHLH expression is both necessary and sufficient for the induction of hypercalcemia and cachexia in preclinical orthotopic cell line tumor models. Consistent with these observations, two different allosteric HIF2 inhibitors, belzutifan and NKT2152, rapidly ameliorated hypercalcemia and cachexia in ccRCC patients, including in some patients who did not exhibit objective tumor shrinkage.

This case highlights the importance of obtaining a thorough medication history, including over-the-counter supplements, when evaluating unexplained metabolic abnormalities. Despite no obvious steroid use, this patient's prolonged use of an unregulated supplement led to the suppression of the HPA axis. While such patients may maintain some baseline cortisol production under normal circumstances, their impaired stress response increases the risk of adrenal crisis during acute illness. Early recognition and prompt management of adrenal insufficiency are crucial in preventing life-threatening complications.

Pancreatic ductal adenocarcinoma (PDAC) is the prototypical cancer type associated with cancer cachexia, a debilitating wasting syndrome marked by adipose tissue loss and muscle atrophy. Herein, we establish that PTHrP is a tumor-derived factor that facilitates cachexia by downregulating de novo lipogenesis in adipocytes and that blocking PTHrP is an effective means to limit wasting in preclinical mouse models.

The follow-up data of our patient after surgical treatment supports the notion that PTHrP-related hypercalcemia does not always indicate a poor prognosis. This case emphasizes the importance of considering benign tumors such as juvenile fibroadenoma as a potential cause of hypercalcemia in adolescents.

DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal-tumor interactions to mitigate bone-invasive OSCC.