Colorectal cancer (CRC) remains a leading cause of death from cancer worldwide, with increasing incidence in the Western world. Diet has become the focus of research as a significant risk factor for CRC occurrence, and the role of dietary polyunsaturated fatty acids (PUFAs) has become an area of interest given their potential role in modulating inflammation, particularly in the pro-carcinogenic inflammatory environment of the colon. This work reviews the main types of PUFAs, their characteristics, structure, and physiologic role. We then highlight their potential role in preventing CRC, their signaling function vis-à-vis tumorigenic signaling, and their subsequent potential role in modulating response to different treatment modalities. We review pre-clinical and clinical data and discuss their potential use as adjunct therapies to currently existing treatment modalities. Given our understanding of PUFAs’ immune and inflammation modulatory effects, we explore the possible combination of PUFAs with immune checkpoint inhibitors and other targeted therapies.

SHP2 (Src Homology 2 Domain-Containing Phosphatase 2) is a protein tyrosine phosphatase widely expressed in various cell types. SHP2 plays a crucial role in different cellular processes, such as cell proliferation, differentiation, and survival. Aberrant activation of SHP2 has been implicated in multiple human cancers and is considered a promising therapeutic target for treating these malignancies. The PTPN11 gene and functions encode SHP2 as a critical signal transduction regulator that interacts with key signaling molecules in both the RAS/ERK and PD-1/PD-L1 pathways; SHP2 is also implicated in T-cell signaling. SHP2 may be inhibited by molecules that cause allosteric (bind to sites other than the active site and attenuate activation) or orthosteric (bind to the active site and stop activation) inhibition or via potent SHP2 degraders. These inhibitors have anti-proliferative effects in cancer cells and suppress tumor growth in preclinical models. In addition, several SHP2 inhibitors are currently in clinical trials for cancer treatment. This review aims to provide an overview of the current research on SHP2 inhibitors, including their mechanism of action, structure-activity relationships, and clinical development, focusing on immune modulation effects and novel therapeutic strategies in the immune-oncology field.

Lymphoid leukemias represent a significant global health burden, leading to substantial morbidity and mortality. The intricate interplay between leukemic cells and their surrounding tumor microenvironment (TME) is pivotal in disease initiation, progression, and therapeutic resistance. Comprising a dynamic milieu of stromal, immune, and leukemic cell populations, the TME orchestrates a complex network of signaling pathways and molecular interactions that foster leukemic cell survival and proliferation while evading immune surveillance. The crosstalk between these diverse cellular components within the TME not only fuels tumor progression but also confers resistance to conventional therapies, including the development of multi-drug resistance (MDR). Recognizing the pivotal role of the TME in shaping disease outcomes, novel therapeutic approaches targeting this dynamic ecosystem have emerged as promising strategies to complement existing anti-leukemic treatments. As a result, drugs that target the TME have been developed as complementary strategies to those that directly attack tumor cells. Thus, a detailed understanding of the TME components and their interactions with tumor cells is critical. Such knowledge can guide the design and implementation of novel targeted therapies for lymphoid leukemias.