**7. Conclusions**

The heterogeneity of tumors has introduced a profound complexity in our understanding of carcinogenesis and the numerous challenges in developing strategies for the treatment of cancer. The recent developments in immunotherapy enable us to devise interventions that promise to improve cancer therapy. Immune checkpoint inhibitors (ICIs) are recently developed drugs that promise to increase overall response. Our evaluation of ICIs shows that the PD-1-PD-L1/L2 pathway is the most targeted pathway. With PD-1 inhibitors in particular having been FDA-approved for the largest variety of cancers. PD-1 inhibitors have been found to have a good response in monotherapy but have recently been frequently tested as part of combinational therapy with other ICIs, such as CTLA-4 and LAG-3. This dual targeting of immune checkpoint proteins has resulted in some of the most promising outcomes. Despite these successes, there are challenges of serious adverse events and the development of resistance. The serious adverse events must be addressed because they are of Grade 3–4. Attempts to overcome them are in progress. Resistance occurs in a significant percentage of patients and therefore urgently needs to be addressed. The two main strategies targeting resistance are the use of combinational therapies and biomarker identification.

#### **Acknowledgements**

BR is funded by Buboo (Pty) Ltd., The Innovation Hub, Hatfield, Gauteng, Pretoria, 0200, South Africa.

STM is funded by the National Research Foundation of South Africa (GUN 121878) and the University of South Africa.

#### **Conflict of interest**

The authors declare no conflict of interest.
