Final answer:
Initially, the neoplasm was not always resistant to chemo agents; cancer cells can develop resistance over time, which led to the development of combination chemotherapy to combat this issue.
Step-by-step explanation:
The neoplasm being referred to in the question was not always resistant to the chemo agents. It is known from the development of cancer chemotherapy that cancer cells have the ability to mutate and potentially develop resistance to single-agent therapy. This was one of the driving factors behind the adoption of combination chemotherapy, pioneered by James F. Holland, Emil Freireich, and Emil Frei in 1965. Their success treating acute lymphoblastic leukaemia (ALL) in children with a multidrug regimen suggested that using multiple drugs with different mechanisms could make it harder for tumors to resist treatment. However, it is important to note that not every cancer cell in a neoplasm may initially be resistant; resistance might develop over time or be present in a subset of cancer cells within the tumor.