Conventional cancer treatments face the challenge of therapeutic
resistance, which causes poor treatment outcomes. The use of combination
therapies can improve treatment results in patients and is one of the
solutions to overcome this challenge. Chemotherapy is one of the
conventional treatments that, due to the non-targeted and lack of
specificity in targeting cancer cells, can cause serious complications
in the short and long-term for patients by damaging healthy cells. Also,
the employment of a wide range of strategies for chemotherapy resistance
by cancer cells, metastasis, and cancer recurrence create serious
problems to achieve the desired results of chemotherapy. Accordingly,
targeted therapies can be used as a combination treatment with
chemotherapy to both cause less damage to healthy cells, which as a
result, they reduce the side effects of chemotherapy, and by targeting
the factors that cause therapeutic challenges, can improve the results
of chemotherapy in patients. Small molecules are one of the main
targeted therapies that can be used for diverse targets in cancer
treatment due to their penetration ability and characteristics. However,
small molecules in cancer treatment are facing obstacles that a better
understanding of cancer biology, as well as the mechanisms and factors
involved in chemotherapy resistance, can lead to the improvement of this
type of major targeted therapy. In this review article, at first, the
challenges that lead to not achieving the desired results in
chemotherapy and how cancer cells can be resistant to chemotherapy are
examined, and at the end, research areas are suggested that more
focusing on them, can lead to the improvement of the results of using
targeted small molecules as an adjunctive treatment for chemotherapy in
the conditions of chemotherapy resistance and metastasis of cancer
cells.