The first Middle East and North Africa expert consensus recommendations for management of advanced gastric cancer.

Gastric cancer (GC) ranks as the fifth most prevalent cancer and the fourth deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, GC represents about 4.8% of cancer cases with more than 35,000 new cases in 2020. To strengthen and improve the management of this cancer in the region, a group of MENA experts in the field of GC developed the first MENA consensus recommendations for the management of advanced GC. A total of 28 statements were drafted, discussed and voted on, using a modified Delphi process, during a virtual consensus meeting. The statements addressed the areas of epidemiology, biomarkers and treatment.

The first Middle East and North Africa expert consensus recommendations for the management of advanced colorectal cancer.

Colorectal cancer (CRC) is ranked as the third most prevalent and the second deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, the number of CRC cases increased over the past decades and will nearly double by 2030. The lack of clear MENA guidelines for the management of patients with CRC represents a step backwards in the fight against this burden. Therefore a panel of 24 MENA experts in the field of gastrointestinal oncology developed, using a Delphi process, the first consensus recommendations for the management of patients with advanced CRC. Forty-seven different statements were formulated in the areas of epidemiology, screening, biomarkers and treatment. These recommendations will guide, standardize and unify the management of this cancer in the MENA region.

Adjuvant therapy in renal cell carcinoma in the immunotherapy era: where do we stand?

Locoregional, as well as metastatic renal cell carcinoma, tends to relapse after nephrectomy or metastasectomy. Adjuvant therapy seems to be an effective strategy to reduce the risk of recurrence. All anti-VEGF tyrosine kinase inhibitors except sunitinib have failed to show any benefit in the adjuvant setting in patients with locally advanced disease and an intermediate-to-high chance of recurrence. On the other hand, immune checkpoint inhibitors, which are now used in the first-line in the metastatic setting, are being tested in the adjuvant setting. Pembrolizumab has shown benefit in the adjuvant setting in patients with a high risk of recurrence or with resected metastatic disease with no evidence of disease. Results for other checkpoint inhibitors are still awaited.

Advanced and metastatic kidney cancer often tend to relapse after surgery. Treatment maintenance after surgery could be an effective strategy to reduce the risk of recurrence. Anti-VEGF tyrosine kinase inhibitors are the standard of care in the treatment of metastatic kidney cancer. However, they have all (but one) failed to prevent the occurrence of metastases in advanced nonmetastatic kidney cancer. On the other hand, immunotherapy is now being tested as a postsurgery treatment to prevent disease recurrence. Pembrolizumab has shown efficacy in preventing recurrence and is now approved as a postsurgery drug in advanced kidney cancer.

Simultaneous inhibition of PD-1 and LAG-3: the future of immunotherapy?

Immunotherapy has improved the prognosis of many cancers, yet a large number of patients have demonstrated resistance to current immune checkpoint inhibitors. LAG-3 is an immune checkpoint expressed on tumor-infiltrating lymphocytes CD4+ and CD8+, Tregs and other immune cells. Coexpression of PD-1 and LAG-3 in solid or hematological cancers is generally associated with a poor prognosis and may be responsible for immunotherapy resistance. Dual inhibition therapy in the RELATIVITY-047 trial significantly improved progression-free survival in metastatic melanoma. This article discusses the presence of a possible synergistic interaction between LAG-3 and PD-1 in the tumor microenvironment and the utility of targeting both immune checkpoint inhibitors as an effective way to bypass resistance and increase treatment efficacy.

Immunotherapy has increased survival rates for many cancer types; however, a large number of individuals experience resistance to this therapy and poor outcomes. Among the immune molecules expressed on immune cells and tumor cells, LAG-3 can favor tumor escape and progression. The coexpression of multiple immune molecules such as PD-1 and LAG-3 in multiple cancers is generally associated with a worse prognosis and might be contributing to immunotherapy failure. Dual inhibition therapy, targeting both PD-1 and LAG-3, in the RELATIVITY-047 study has shown great antitumor activity and improved survival in metastatic melanoma. This report discusses a possible synergistic interaction between LAG-3 and PD-1 within the tumor and the utility of targeting both molecules as a way to overcome resistance and improve treatment efficacy.

KRAS-G12C covalent inhibitors: A game changer in the scene of cancer therapies.

RAS is the most frequently mutated oncogene in human cancer. Scientists attempted for decades to target this protein or its pathways, however, all the attempts failed and RAS was labeled as "undruggable". With KRAS-G12C covalent inhibitors entering clinical trials, the myth of this "undruggable" RAS is fading away. In 2021, the Food and Drug Administration (FDA) approved the use of Sotorasib (Lumakras) for the treatment of adult patients with KRAS-G12C mutated locally advanced or metastatic NSCLC, following at least one prior systemic therapy. However, and as every other drug, KRAS-G12C inhibitors are facing intrinsic and acquired resistances. In order to overcome these resistances, researchers are now working on combination strategies. Furthermore, studies are currently ongoing to better elucidate the status of KRAS-G12C as a predictive and prognostic tool and to strengthen its role in the field of personalized medicine.