Development of point-of-care (POC) biosensors for detection of cancer biomarkers is a crucial topic for enabling early detection of cancer occurrence and monitoring its progression. Our results showcase cost- effective solutions for detection of human epidermal growth factor receptor 2 (HER2) based on custom-made gold leaf electrodes (GLEs) and Matrix proteinase 2 (MMP2) detection based on graphene-functionalized commercial screen-printed gold electrodes. Overexpressed HER2 biomarker has been classified as both a prognostic and predictive biomarker for breast cancer while MMP-2 is a protein that is typically overexpressed in tumor tissues, with important roles in tumor invasion, metastasis as well as in tumor angiogenesis. Different novel strategies are employed for optimization of the surface functionalization with suitable proteins, antibodies, and aptamers to achieve highly sensitive and specific interaction with cancer biomarkers. Electrochemical characterization was performed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) and the potential of biomarker-sensing was examined in phosphate buffer saline (PBS) and in a cell culture medium. The proposed solution showed good specificity and high sensitivity of HER2 detection without any enrichment steps, achieving a limit of detection (LOD) of 0.02 ng/mL in PBS and 0.03 ng/mL in cell culture medium, making the proposed sensor a cost-effective and sensitive candidate for detection in complex biological matrices. In case of the MMP-2 sensor, based on impedimetric measurements, we could detect as low as 3.32 pg/mL of MMP-2 in PBS with a wide dynamicrange of 1 pg/mL – 10 ng/mL. Besides high specificity, rGO-based aptasensor showed a potential for reuse due to demonstrated successful signal restoration after experimental detection of MMP-2. These novel cost-effective biosensing systems represent a promising step toward future application for POC detection of HER2 and MMP2 cancer biomarkers.