Challenges of cancer survivorship care in Chile: a longitudinal study comparing the quality of care and quality of life for cancer survivors in a primary care network and a cancer centre in Chile

Objective

The rapid growth in the cancer survivor population in Chile and Latin America raises new challenges in addressing their care needs. This study assesses the health status and compares the quality of care and quality of life in cancer survivors at a primary care network and a private cancer centre in Santiago, Chile.

Design

Retrospective cohort study.

Setting

Three primary care clinics and one cancer centre in Chile.

Participants

All breast and colorectal cancer patients identified from a primary care retrospective cohort of 61 174 were followed from 2018 to 2023 and compared with an equivalent sample of patients from a university cancer centre identified during the same period.

Outcome measures

Quality of care was assessed based on American Cancer Society standards, while quality of life was measured using the EuroQol 5 Dimensions-5 Levels survey instrument.

Results

A total of 420 cancer survivors participated in the study; 208 from primary care and 212 from the cancer centre. All participants received substandard care. Patients in primary care had lower educational levels and higher rates of comorbidity. They reported a lower quality of life score (72.22 vs 78.43, p

Conclusion

Cancer survivors face a significant disease burden and receive substandard care in Chile. As the primary source of care for this population, primary care is challenged to better integrate with speciality care to develop an effective shared care model for cancer survivors.

Daraxonrasib, a pan-RAS inhibitor, selectively inhibits osteosarcomas with activated KRAS by halting AKT signaling and matrix metalloprotease activity

by Okkeun Jung, Angelene Soto, Andrew L. Wolfe, Shahana S. Mahajan

KRAS mutations, which induce proliferative signaling driving many human cancers, are detectable in a small subset of osteosarcoma patients. The recently developed pan-KRAS inhibitor daraxonrasib, also known as RMC-6236, is capable of targeting a wide array of KRAS mutations and shows promise against pancreatic and lung cancers. However, the efficacy and mechanisms of action of daraxonrasib in osteosarcoma (OS) remain unclear. We evaluated the effects of daraxonrasib on the viability, proliferation, and metastatic potential of wild-type and KRAS mutant OS cells. We assayed the effects of treatment on downstream targets using qPCR, immunoblotting, and activity assays to explore the underlying mechanism by which daraxonrasib selectively suppresses the metastatic potential of KRAS mutant osteosarcoma. Finally, we investigated how the increased prevalence of GTP-bound KRAS enhanced the sensitivity of KRAS wild-type osteosarcoma cells to daraxonrasib using siRNA targeting RASA1. Daraxonrasib selectively attenuated the proliferation and migratory ability of KRAS mutant HOS-143B cells without affecting KRAS wild-type controls. Additionally, daraxonrasib suppressed the expression of the matrix metalloproteases MMP9 and MMP1, which promote cell motility and metastasis. Daraxonrasib selectively inhibited the AKT/ETS1 pathway in HOS-143B cells, whereas no such effect was observed in HOS cells. HOS cells were sensitized to daraxonrasib by knocking down the GTPase-activating protein RASA1. In osteosarcoma, KRAS inhibition decreased MMP1, MMP9, and AKT/ETS1 signaling. Daraxonrasib is a promising agent for treating osteosarcoma with KRAS mutations.